Pill Group Research Articles

Preoperative Planning of Lumbar Lordosis for Adult Degenerative Scoliosis Surgery in the Chinese Population

Pelvic incidence minus lumbar lordosis mismatch (PI-LL) is directly related to poor quality of life in adult degenerative scoliosis (ADS) patients. The purpose of the study was to determine the most appropriate postoperative PI-LL value for patients with ADS. The medical records of patients with ADS in our department were retrospectively collected. The data included age, sex, body mass index, age-adjusted Charlson comorbidity index, osteopenia, length of hospital stay, operative duration, estimated blood loss, American Society of Anesthesiologists score, number of fusion levels, lumbar lordosis, sagittal vertical axis, pelvic incidence, PI-LL, Scoliosis Research Society-22 score, Oswestry Disability Index score, and mechanical complications. A total of 316 patients were enrolled. PI-LL, lumbar lordosis, sagittal vertical axis, Scoliosis Research Society-22 score, Oswestry Disability Index score at the time of last follow-up were 20.7 ± 8.5°, 23.4 ± 14.1°, 4.0 ± 2.1cm, 3.7 ± 0.9, and 18.1 ± 5.5, respectively. In terms of mechanical complications, 88 patients (27.8%), 34 patients (10.8%), and 19 patients (6.0%) had proximal junctional kyphosis, distal junctional kyphosis, and implant-related complications, respectively. In the fully adjusted model, compared with 0 grade PI-LL group and++ grade PI-LL group,+ grade PI-LL group had the best clinical outcomes and the fewest mechanical complications. The stability of these conclusions was verified in sensitivity analyses. Optimal PI-LL value should be 10°-20° after corrective surgery in patients with ADS, which is associated with excellent clinical outcomes and lower complication rates. Previous criteria may be at risk of overcorrection, which may lead to proximal junctional kyphosis.

Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease.

To investigate the effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease. In the study conducted at Heping Hospital of Changzhi Medical College from March 2021 to December 2022, 30 cases of patients diagnosed with diabetic nephropathy were meticulously selected as study subjects. Employing a double-blind randomized table method, these patients were randomly allocated into three groups: the control group (n = 10), the Bifidobacterium bifidum tetragonum tablets group (n = 10), and the Jin Gui Ren Qi Pill group (n = 10). The control group received standard western medical treatments for diabetic nephropathy, including serum glucose, blood lipids, blood pressure management, and other conventional therapies. In addition to the standard treatments, the Bifidobacterium bifidum tetragonum tablets group received Bifidobacterium bifidum tetragonum tablets, while the Jin Gui Ren Qi Pill group received Jin Gui Ren Qi Pill. Before and after a 4-week treatment period, various baseline parameters were assessed, including fasting blood glucose, 2-h postprandial blood glucose, triglycerides, serum total cholesterol, serum low-density lipoprotein cholesterol, serum high-density lipoprotein cholesterol, random urine microalbumin/creatinine ratio (ACR), blood creatinine (SCr), and traditional Chinese medicine evidence scores. Stool specimens were collected from all three groups before and after treatment for 16S rDNA high-throughput sequencing, followed by comprehensive analyses including OUT clustering, Alpha diversity, Beta diversity, species composition analysis, LEfSe analysis, and KEGG function prediction. Spearman correlation analysis was employed to explore the relationship between intestinal flora and clinical indicators. Furthermore, fasting peripheral venous blood was collected from patients in the Bifidobacterium tetrapunctate tablets group and the control group before and after intervention to measure the optical density values of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) using the Beijing Biolite ELISA kit. This study was conducted with the approval of the Ethics Committee of Changzhi Medical College. 1. The 2hPBG, total cholesterol and LDL levels were observed among patients with diabetic kidney disease (DKD) across all groups: the Jin Gui Ren Qi Pill group, the Bifidobacterium bifidum tetragonum tablets group, and the control group (p < 0.05). 2. The Jin Gui Ren Qi Pill demonstrated superior efficacy in alleviating TCM symptoms and reducing the ACR compared to both the Bifidobacterium bifidum tetragonum tablets group and the control group. Conversely, Bifidobacterium bifidum tetragonum tablets exhibited a more pronounced reduction in TC levels compared to both the Jin Gui Ren Qi Pill and control groups. Notably, Bifidobacterium bifidum tetragonum tablets effectively decreased (IL-2) levels in patients with DKD. 3. Bifidobacterium bifidum tetragonum tablets also demonstrated efficacy in reducing IL-2 levels in DKD patients. 4. Analysis of intestinal microorganism abundance and diversity before and after the intervention, as well as among the three groups, revealed no significant alterations. Similarly, comparisons of ACE, Chao, Simpson, and Shannon indices showed no statistically significant differences (p > 0.05). 5. Qualitative analysis of intestinal microorganisms before and after intervention, as well as among the three groups, indicated no significant differences. Anosim test results also did not reveal qualitative distinctions (Anosim test R = 0.021, p = 0.215). 6. LEfSe analysis unveiled a noteworthy increase in Prevotella_7 abundance within the Jin Gui Ren Qi Pill group post-intervention (p < 0.05). 7. Furthermore, Chinese medicine evidence scores, body mass index, TC, and LDL levels correlated positively with the relative abundance of Tyzzerella_3 bacterial flora. Conversely, age, disease duration, and 2hPBG correlated positively with the relative abundance of Christensenellaceae_R_7 flora, while TC and LDL levels displayed a negative correlation with the relative abundance of Christensenellaceae_R_7 flora. The combination of Jin Gui Ren Qi Pill with western medical treatment exhibited superior efficacy in ameliorating clinical symptoms and reducing the ACR in patients with DKD compared to western medical treatment alone. Furthermore, this combination therapy led to an increase in the abundance of Prevotella_7 within the intestinal flora of patients, suggesting a potential enhancement in carbohydrate metabolism by the intestinal microbiota. On the other hand, Bifidobacterium bifidum tetragonum tablets bacterial tablets combined with western medical treatment demonstrated enhanced efficacy in reducing TC levels in DKD patients compared to western medical treatment alone. Additionally, this combination therapy effectively reduced the levels of IL-2 in DKD patients, thus mitigating inflammation in these individuals.

Dingxian pill alleviates hippocampal neuronal apoptosis in epileptic mice through TNF-α/TNFR1 signaling pathway inhibition

Ethnopharmacological relevanceDingxian Pill (DXP), a famous traditional Chinese medicine prescription, and has been widely proven to have positive therapeutic effects on “Xianzheng” (the name of epilepsy in ancient China). However, the anti-epileptic molecular mechanisms of DXP are not yet fully understood and remain to be further investigated. Aim of the studyTo elucidate the molecular mechanism of DXP's improvement in epileptic neuronal loss, damage and apoptosis by regulating TNF-α/TNFR1 signaling pathway. Materials and methodsSixty Kunming mice were randomly divided in 6 groups: control group (equal volume of normal saline), model group (180 mg kg−1 pilocarpine hydrochloride – used to establish the epilepsy animal model), carbamazepine group (30 mg kg−1), and low, medium, and high-dose Dingxian Pill groups (4.08, 8.16, and 16.32 g kg−1, respectively – oral administration once daily for 2 weeks). Successful establishment of the epileptic mouse model was monitored with electroencephalography. Pathological changes in hippocampal tissue were analyzed with hematoxylin-eosin staining. Hippocampal neuronal apoptosis was analyzed with TUNEL staining. TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein expression levels in hippocampal tissue were analyzed with real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blot, respectively. Cleaved caspase-8 protein levels in hippocampal tissue were measured with immunohistochemistry and Western blot. ResultsCompared to control, the model group showed an increase in continuous epileptic discharge waves on EEG, a damaged hippocampal neuron morphological structure, increased hippocampal neuronal apoptosis, and significantly increased TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein levels, and increased caspase-8 cleavage (P < 0.05). Compared to the model group, the carbamazepine group as well as the low-, medium-, and high-dose Dingxian Pill groups showed decreased epileptic discharges on EEG, an obvious hippocampal neuron morphological structure restoration, varying degrees of attenuated hippocampal neuronal apoptosis, and significantly decreased TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein levels as well as decreased caspase-8 cleavage (P < 0.05). ConclusionsDingxian Pill exerts an anti-epileptic effect through inhibition of TNF-α/TNFR1 signaling pathway-mediated apoptosis in hippocampal neurons.

Ideal Lumbar Lordosis Correction in Patients with Adult Spinal Deformity Without Adversely Impacting Pelvic Tilt and Pelvic Incidence Minus Lumbar Lordosis: A Study of 426 Cases.

Retrospective study. To determine the ideal pelvic incidence (PI) - lumbar lordosis (LL) range to prevent pelvic tilt (PT) undercorrection while avoiding PI-LL overcorrection following adult spinal deformity (ASD) surgery. PI-LL and PT are the important sagittal parameters to be restored to an adequate range by surgery. Ideal PI-LL target without causing PI-LL overcorrection and PT undercorrection has not been documented. We included patients with ASD undergoing ≥5-level fusion including the sacrum. Receiver operating characteristic (ROC) curve analysis was performed to calculate the lower limit of the ideal PI-LL without causing PI-LL overcorrection and the upper limit of ideal PI-LL without causing PT undercorrection. The calculated ideal PI-LL was validated in terms of proximal junctional kyphosis and failure (PJK and PJF) rates and clinical outcomes. Analyses were performed according to age subgroups (<70 and ≥70y). In total, 426 patients were included in the study. Female patients were predominant (85.4%), with a mean age of 69.8 years. The lower limits of PI-LL were calculated as 4.9° for all patients, 2.3° for patients aged <70 years, and 7.9° for patients aged ≥70 years. Meanwhile, the upper limits of PI-LL were calculated as 12.7° for all patients, 12.5° for patients aged <70 years, and 13.3° for patients aged ≥70 years. There were no significant differences in the PJK and PJF rates among the new three PI-LL groups. Clinical outcomes were significantly better in patients with the ideal PI-LL group than those in patients with overcorrection or undercorrection groups for all age groups. The ideal PI-LL correction target without adversely impacting PT and PI-LL was calculated at 2.3°-12.5° for patients aged <70 years and 7.9°-13.3° for patients aged ≥70 years. These guideline parameters may help ensure optimal clinical outcomes without increasing the risk of PJK/F.

Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial

ObjectivesTo evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.DesignThe PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel...

Calming effect of traditional Chinese medicine cinnabar based on neurotransmitter content and metal elements concentration in PCPA-induced insomnia rats

IntroductionCinnabar is a commonly utilized mineral traditional Chinese medicine (TCM) in China. It has the functions of clearing the heart and calming the mind. However, there remains a dearth of pharmacological experiments on the metal elements of cinnabar on animal models. Therefore, this study aims to investigate the effects of cinnabar on neurotransmitter levels in p-chlorophenylalanine (PCPA) induced insomnia rats and the content of metal elements in plasma, heart, liver, spleen, lung and kidney of rats. MethodsTissue hematoxylin and eosin (H&E) staining were used to assess the histological changes. The 5-HT and GABA in plasma and hypothalamus of rats were determined by enzyme-linked immunosorbent to evaluate the therapeutic effect. The content of metal elements in plasma, heart, liver, spleen, lung and kidney of rats was determined by ICP-MS. ResultsAfter cured with cinnabar and its processed for fourteen days, the level of 5-HT in the plasma and hypothalamus increased (P<0.05), and the level of GABA decreased (P<0.05). Furthermore, both low dose (1 mg/kg) and high dose (10 mg/kg) of cinnabar resulted in an increase in plasma 5-HT levels;, however, the high dose of cinnabar increased the level of 5-HT more than low dose of cinnabar. The content of metal elements in plasma, hemocyte and heart, liver, spleen, lung and kidney of rats ranged from less than 1 µg.g−1 to hundreds of µg.g−1, among which the highest content was Fe in rat's spleen of cinnabar sedative pill group, and the content is 919 µg.g−1. The content of most metal elements in plasma and hemocyte of rats was significantly lower than that in heart, liver, spleen, lung and kidney. There is no obvious difference of Hg in plasma and tissue of rats between the control group fed normally and rats fed with drugs. DiscussionCinnabar and its products can improve insomnia symptoms in rats by regulating the neurotransmitters 5-HT and GABA. Cinnabar is basically non-toxic in short-term (less than 14 days) use accordance with the dosage prescribed by pharmacopoeia.

Effect of Shoutai Pills on expression of key glycolytic proteins and apoptosis related factors at maternal fetal interface in mouse model of threatened abortion with syndrome of kidney deficiency

This study aims to explore the mechanism of Shoutai Pills in treating threatened abortion. According to the random number table method, ICR female mice were randomized into a normal group, a model group, a dydrogesterone group, and a Shoutai Pills group, with 15 mice in each group. Mice were administrated with normal saline(normal and model groups) or the suspension of Shoutai Pills or dydrogesterone by gavage at 9:00 am every day. At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days. ICR female and male mice were caged in a ratio of 2∶1 during the pre-estrous or estrous period. From the first day of pregnancy, drug administration was continued for 5 consecutive days. On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion. On day 6 of pregnancy, 10 female ICR mice were randomly selected from each group, and the uterus was collected for observation of the pathological changes of trophoblasts at the maternal-fetal interface by hematoxylin-eosin(HE) staining. The protein levels of key enzymes of glycolysis, hexokinase 2(HK2), enolase 1(ENO1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A(LDHA), were determined by Western blot and immunofluorescence. The expression of apoptosis-related proteins including B cell lymphoma-2(Bcl-2), Bcl-2-associated protein X(Bax), and cysteinyl aspartate-specific proteinase-3(caspase-3) was determined by Western blot and real-time PCR. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling was employed to examine apoptosis. The embryo loss rate of the remaining five female mice was calculated by trypan blue staining method on day 14 of pregnancy. On day 14 of pregnancy, the embryo loss rate of the normal group was 5.00%, which was lower than that(27.78%) in the model group(P&lt;0.05). Dydrogesterone and Shoutai Pills groups showed reduced embryo loss rates(10.26% and 7.50%, respectively) compared with the model group. On day 6 of pregnancy, compared with the normal group, the model group showed down-regulated expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and up-regulated expression of Bax and caspase-3(P&lt;0.05). Compared with the model group, dydrogesterone and Shoutai Pills up-regulated the expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and down-regulated the expression of Bax and caspase-3(P&lt;0.05). Compared with that in the normal group, the apoptosis rate in the model group increased(P&lt;0.05). Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P&lt;0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.

Qi-Ju-Di-Huang-Pill delays the progression of diabetic retinopathy

Ethnopharmacological relevanceQi-Ju-Di-Huang-Pill (QJDH pill) is a Chinese decoction. Although it is commonly used to treat eye conditions, such as diabetic retinopathy (DR), its exact mechanism of action is unknown. Aim of the studyTo investigate the specific mechanism by which QJDH pill slows the progression of diabetic retinopathy (DR) based on animal and cellular experiments. Material and methodsThe major components of QJDH pill were characterized by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLCMS/MS). C57BL/6J mice were randomly divided into five groups as follows: normal group (control group), model group (STZ group), low-dosage QJDH pill group (QJDH-L group), medium-dosage QJDH pill group (QJDH-M group) and high-dosage QJDH pill group (QJDH-H group). Changes in water intake, urination, food intake, and body mass were monitored weekly, while changes in blood glucose were monitored monthly. Fluorescein fundus angiography (FFA), optical coherence tomography angiography (OCTA), and optical coherence tomography (OCT) were utilized to analyze the changes in fundus imaging indications. Hematoxylin & eosin (H&E) and transmission electron microscopy (TEM) were employed to examine histopathologic and ultrastructural changes in retina. The levels of interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) in peripheral blood were detected using Enzyme-linked immunosorbent assay (ELISA). The mouse retina apoptotic cells were labeled with green fluorescence via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (Tunel). The protein levels of Bcl-2-Associated X (Bax), B cell lymphoma 2 (Bcl-2), Caspase-3, PI3K, phosphorylated PI3K (p-PI3K), protein kinase B (AKT) and phosphorylated AKT (p-AKT) were quantified by Western blot (WB). The retinal pigment epithelium (RPE) cells were cultured and classified into five groups as follows: normal glucose group (NG group), high glucose group (HG group), high glucose + QJDH pill group (HG + QJDH group), high glucose + inhibitor group (HG + LY294002 group), and high glucose + inhibitor + QJDH pill group (HG + LY294002 + QJDH group). Cell viability and apoptosis were detected via Cell Counting Kit-8 (CCK8) and then analyzed by flow cytometry. ResultsIn vivo experiments revealed that the QJDH pill effectively reduced blood glucose, symptoms of increased water intake, elevated urination, increased food intake and decreased body mass in DR mice. QJDH pill also slowed the development of a series of fundus imaging signs, such as retinal microangiomas, tortuous dilatation of blood vessels, decreased vascular density, and thinning of retinal thickness, downregulated IL-6, IL-17, TNF-α, and VEGF levels in peripheral blood, and inhibited retinal cell apoptosis by activating the PI3K/AKT signaling pathway. Moreover, in vitro experiments showed that high glucose environment inhibited RPE cell viability and activated RPE cell apoptosis pathway. In contrast, lyophilized powder of QJDH pill increased RPE cell viability, protected RPE cells from high glucose-induced damage, and decreased apoptosis of RPE cells by activating the pi3k pathway. ConclusionQJDH pill induces hypoglycemic, anti-inflammatory effects, anti-VEGF and anti-retinal cell apoptosis by activating PI3K/AKT signaling pathway, and thus can protect the retina and slow the DR progression.

A randomized clinical trial of transdermal (gel) versus oral estrogen for endometrial preparation in frozen embryo transfer cycle.

The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

Optical Coherence Tomography Angiography: Investigating Vessel Density Changes Induced by Caffeine in Healthy Subjects.

Introduction: Caffeine, the most widely consumed psychoactive drug globally, has been associated with vascular changes in various organs, including the retina. Researchers have reported vascular constriction in the retina in response to caffeine, although data on its effects remain limited and somewhat contradictory. Further research is needed to clarify the specific impact of caffeine on retinal blood vessels and its potential implications for ocular health. Purpose: To investigate the effects of 200 mg of caffeine on systolic and diastolic blood pressure (SBP and DBP) and retinal vessel density (VD) assessed by optical coherence tomography angiography (OCTA). Methods: Prospective randomized, double-blind placebo-controlled, IRB-approved study in 59 healthy low caffeine users (< 136 mg of caffeine daily). Baseline 3 × 3 and 6 × 6 mm OCTA scans centered on the fovea as well as a 6 × 6 mm scans centered on the optic nerve head (ONH) were obtained. Participants were randomly assigned into caffeine group (CG, n = 42) receiving 200 mg caffeine pill or placebo group (PG, n = 17). OCTA scans were repeated at 60 and 120 min after intervention. VD was measured with Advanced Retina Imaging (ARI) network software (Carl Zeiss Meditec, Dublin, CA) for superficial capillary plexus (SCP) and deep capillary plexus (DCP). SBP/DBP readings were recorded before each imaging session. Ordinary one-way analysis of variance (ANOVA) of each group was performed using GraphPad Prism Version 9.3.0. Results: Both groups had comparable demographics and OCTA parameters at baseline. Two hours after intervention, the CG had a significantly higher SBP (123 ± 7 mmHg) and DBP (81 ± 5 mmHg) compared to the control group (118 ± 7 mmHg, 77 ± 6 mmHg) (p value = 0.012, 0.023). Regarding the OCTA VD metrics, there were no significant differences in VD between the caffeine and placebo groups, regardless of whether the scans were centered on the macula or ONH. Additionally, the comparison across different OCTA scan modalities, specifically the 3 × 3 mm and 6 × 6 mm scans, showed no discernible differences among groups. Conclusion: In conclusion, 200 mg of caffeine elevated blood pressure after 2 h but did not impact the retinal VD. This underscores the intricate relationship between caffeine, blood pressure, and retinal vascular dynamics, prompting further exploration of their implications for ocular health, especially in subjects with vascular disease.

Zuogui Pills improve testicular development of offspring rats exposed to prenatal stress via Cx43

This study aims to reveal the mechanism of prenatal stress in affecting the testicular development of offspring rats and the intervention effects of Zuogui Pills via connexin 43(Cx43). Forty pregnant SD rats were randomized into a blank control group, a mo-del group, a high-dose(18.9 g·kg~(-1)) Zuogui Pills group, a low-dose(9.45 g·kg~(-1)) Zuogui Pills group, and a vitamin E(1.44 mg·kg~(-1)) group. The other groups except the blank control group was subjected to chronic unpredictable mild stress for the modeling of prenatal stress. The model was evaluated by sucrose preference test, open field test, and enzyme-linked immunosorbent assay(ELISA) of the glucocorticoid level. ELISA was employed to measure the thyroxine 4(T4), testosterone(T), and follicle-stimulating hormone(FSH) levels to assess kidney deficiency. Hematoxylin-eosin(HE) staining was employed to evaluate the status of testicular germ cells. An automatic sperm analyzer was used to measure the sperm quality. Immunofluorescence double staining was employed to detect the expression of Cx43 and follicle-stimulating hormone receptor(FSHR) in the testes of offspring rats. The mRNA and protein levels of Cx43, FSHR, phosphatidylinositol 3-kinase(PI3K), and protein kinase B(Akt) were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. Prenatal stress induced testicular development disorders in offspring rats. The HE staining results showed that on the day of birth, the model group had reduced seminiferous tubules in the testes, elevated FSH level in the serum, and lowered Cx43 level in the testicular tissue. Male offspring rats of 60 days old had reduced testicular spermatogenic function, decreased sperm quality, elevated FSH level and lowered T level in the serum, and down-regulated protein and mRNA levels of Cx43, FSHR, PI3K, and Akt in the testicular tissue. Zuogui Pills alleviated the abnormal development and dysfunction of testicles in the offspring rats caused by prenatal stress. In summary, Zuogui Pills may weaken the effects of prenatal stress on testicular development and spermatogenic function of offspring rats by activating the PI3K/Akt pathway to regulate Cx43 expression in the testicular tissue.

Neutral effect of Zishen Yutai Pill on frozen-thawed embryo transfer: a propensity score matching study.

To investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles. A retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate. After propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model. The use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.

Compensatory versus Rehabilitative Dysphagia Management Approaches are More Frequently Recommended in Hospitalized Persons with Alzheimer’s Disease and Related Dementias

AbstractBackgroundPersons with Alzheimer’s disease and Related Dementias (AD/ADRD) frequently develop difficulty swallowing (dysphagia). Two general categories of dysphagia management approaches are initiated by Speech‐Language Pathologists (SLP): compensatory (e.g., modifying fluid/food characteristics) and rehabilitative (exercise‐based). While compensations may improve swallowing safety (no airway invasion) and efficiency (no residue) in the short term, they do not actively target swallowing muscles (e.g. rehabilitative approaches) to induce lasting change in physiology. Additionally, compensatory recommendations are often based on clinical examinations (Desai, 2020) that do not permit visualization of swallowing possible with instrumental assessment (e.g. videofluoroscopic swallow study, ‘VFS’) which may lead to recommendations that are misaligned with swallowing physiology. This study aimed to elucidate whether the frequency of compensatory versus rehabilitative recommendations differs based on VFS findings. Specifically, we sought to characterize: 1) dysphagia management recommendations and 2) VFS findings contributing to these recommendations in a cohort of hospitalized patients with AD/ADRD.MethodThe retrospective sample included all inpatients (n = 122) with AD/ADRD (≥50 years) referred for a VFS at an academic hospital in 2014. AD/ADRD was determined by a diagnosis in the EHR and/or if the patient was taking medication(s) prescribed for AD/ADRD. Dysphagia management recommendations and VFS outcomes including swallowing safety (Penetration‐Aspiration Scale (Rosenbek, 1995) ‘PAS’ scores), efficiency (oropharyngeal residue), and biomechanical impairments (as identified by the SLP) were abstracted from the EHR. The absence (PAS scores 1,2, or 4) or presence (PAS scores 3,5,6, 7, or 8) of airway invasion was further classified (Steele, 2017). Descriptive statistics were calculated to analyze the data.ResultAll recommendations were compensatory with no rehabilitative treatments offered (Table 1). Across recommendations, pharyngeal phase impairments (e.g., pharyngeal delay) and inefficiency (e.g., vallecular residue) on VFS were more common than oral phase impairments/inefficiency. While relatively infrequent, airway invasion was most observed in the pill, solid, and liquid modification groups (Table 2).ConclusionIn this cohort, all dysphagia treatment recommendations were compensatory approaches focused on optimizing swallowing safety and efficiency. While these recommendations were aligned with VFS findings reflecting pharyngeal phase impairments/inefficiency, they highlight a missed opportunity to address swallowing impairments by directly targeting underlying physiology with a rehabilitative approach.

Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

Urine metabolomics study of intervention of Xihuang Pills in rats with hyperplasia of mammary gland

This study aimed to investigate the mechanism of Xihuang Pills in improving hyperplasia of mammary gland(HMG) in rats based on urine metabolomics using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS). The HMG rat model was established by intramuscular injection of estradiol benzoate solution(0.5 mg·kg~(-1), 25 days) followed by progesterone injection(5 mg·kg~(-1), 5 days). UPLC-Q-Orbitrap-MS technology was used to establish the endogenous small-molecule metabolic profiles in urine samples of rats in the blank group, the HMG model group, and Xihuang Pills group. Multivariate statistical analysis was performed for pattern recognition, t test and variable importance in the projection(VIP) were used to screen potential biomarkers. The significantly changed differential metabolites were identified using the online database Human Metabolome Database(HMDB). Metabolic pathway enrichment analysis was conducted using the MetaboAnalyst 5.0 database. The results showed that 90 differential metabolites with significant changes(P&lt;0.05) were identified between the blank group and the HMG model group using the HMDB. Among them, 48 metabolites significantly reverted(P&lt;0.05) after administration of Xihuang Pills, which may be related to the regulatory effect of Xihuang Pills. Thirteen metabolic pathways significantly associated with HMG were identified when the differential metabolites were imported into the MetaboAnalyst 5.0 database, and Xihuang Pills could modulate seven of these pathways. These metabolic pathways mainly involved histidine metabolism, arginine and proline metabolism, β-alanine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, pyrimidine metabolism, and amino sugar and nucleotide sugar metabolism. This study utilized UPLC-Q-Orbitrap-MS and urine metabolomics technology to analyze the mechanism of Xihuang Pills in improving HMG, laying the foundation for further in-depth research.

Research on mechanism of novel isoflavone F11 in protecting rotator cuff injury through vascular endothelial growth factor signal pathway

This study discusses the mechanism of novel isoflavone F11 in protecting rotator cuff injury through vascular endothelial growth factor (VEGF) signal pathway. 60 rats were assigned into sham group, RCT group, low F11 group, middle F11 group, high F11 group, and huqian pill group. The level of IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) was detected with enzyme-linked immunosorbent assay (ELISA) method. The max load was detected with MTS biomechanics experiment. The pathological form of tissue was detected with HE staining method. The expression of VEGF and basic fibroblast growth factor (BFGF) was detected with western blot and real-time reverse transcription–polymerase chain reaction (RT-PCR). The level of IL-1β, IL-6 and TNF-α in RCT group was higher than that in sham group. The max load was reduced. Their level in low F11 group, middle F11 group, high F11 group and huqian pill group was lower than RCT group with a significant difference in max load. VEGF and BFGF expression in RCT group was lower than sham group. It was increasing along with the increasing concentration of adopted F11. The level of inflammation in serum was reduced with F11. The biomechanics of bone could be increased. Thus, it could develop protecting action on rotator cuff injury through activating the level of VEGF.

Intestinal mucosal flora of the intestine-kidney remediation process of diarrhea with deficiency kidney-yang syndrome in Sishen Pill treatment: Association with interactions between Lactobacillus johnsonii, Ca2+-Mg2+-ATP-ase, and Na+-K+-ATP-ase

This study aims to investigate the effect of Sishen Pill on the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Fifteen Kunming male mice were randomly divided into Normal control group (C), Model self-healing group (X) and Sishen Pill group (S), with 5 mice/cages. Hematoxylin eosin (HE) staining was used to observe the kidney structure. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA), Analysis of intestinal mucosal flora using third-generation high-throughput sequencing. The relative abundance results in the three groups revealed that the dominant bacterial genera: Lactobacillus, Muribaculum and Candidatus-Arthromitus; bacterial species: Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus murinus, and Lactobacillus intestinalis, and differences in the presence of major microbiota between the X and S groups. A positive correlation between Lactobacillus johnsonii and both Ca2+-Mg2+-ATP-ase and Na+-K+-ATP-ase was found via correlation analysis. Sishen Pill also changed the manufacture of other secondary metabolites, as well as the metabolism of carbohydrates, glycans, energy, lipids, and other amino acids, and xenobiotics biodegradation and metabolism. In conclusion, Sishen Pill improved kidney structure, energy metabolism and the diversity and structure of intestinal mucosal flora. In addition, Lactobacillus johnsonii may be a characteristic species of Sishen Pill in treating diarrhea with kidney-yang deficiency syndrome.

The effects of exogenous estrogen in women with SAR-CoV-2 infection: a systematic review and meta-analysis

Does exogenous estrogen use affect COVID-19-related mortality in women? Menopausal hormone therapy (MHT) was associated with a lower likelihood of all-cause fatality related to COVID-19in postmenopausal women (odds ratio (OR) 0.28, 95% CI 0.18, 0.44; 4 studies, 21 517 women) but the combined oral contraceptive pill in premenopausal women did not have a significant effect (OR 1.00, 95% CI 0.42-2.41; 2 studies, 5099 women). Men are much more likely to die from COVID-19 than women. In this systematic meta-analysis, a literature search was conducted using the following search terms related toCOVID-19 and estrogen, sex hormones, hormonal replacement, menopause, or contraception. The PubMed, Scopus, Cochrane Library, and EMBASE databases were searched to identify relevant studies published between December 2019 and December 2021. We also searched MedRxiv as a preprint database and reviewed the reference lists of all included studies and clinical trial registries for ongoing clinical studies until December 2021. All comparative studies that compared the rates mortality and morbidity (hospitalization, intensive care unit (ICU) admission, and ventilation support) due to COVID-19 in women using exogenous estrogen to a control group of women (nonusers) were included. A review of the studies for inclusion, extraction of data, and assessment of the risk of bias was performed independently by two reviewers. The ROBINS-I tool and the RoB 2 tool were used for bias assessment of the included studies. Pooled odds ratios (ORs) with 95% CIs were calculated using Review Manager V5.4.1. The I2 statistic was used to quantify heterogeneity. The quality of the evidence was assessed using GRADE criteria. After searching the databases, we identified a total of 5310 studies. After removing duplicate records, ineligible studies, and ongoing studies, a total of four cohort studies and one randomized controlled trial comprising 177 809 participants were included in this review. There was a moderate certainty of evidence that MHT was associated with a lower likelihood of all-cause fatality related to COVID-19 (OR 0.28, 95% CI 0.18, 0.44; I2 = 0%; 4 studies, 21 517 women). The review indicated a low certainty of evidence for other outcomes. The mortality rate of premenopausal women in the combined oral contraceptive pill group did not differ significantly from the control group (OR 1.00, 95% CI 0.42-2.41; 2 studies, 5099 women). MHT marginally increased the rate of hospitalization and ICU admission (OR 1.37, 95% CI 1.18-1.61; 3 studies, 151 485 women), but there was no significant difference in the need for respiratory support between MHT users and nonusers (OR 0.91, 95% CI 0.52-1.59; 3 studies, 151 485 women). Overall, the tendency and magnitude of the effects of MHT in postmenopausal women with COVID-19 were consistent across the included studies. The certainty of the evidence for other outcomes of this review may be limited, as all included studies were cohort studies. In addition, the dosages and durations of exogenous estrogen used by postmenopausal women varied from study to study, and combined progestogen administration may have had some effect on the outcomes. The findings of this study can aid in counseling postmenopausal women taking MHT when they are diagnosed with COVID, as they have a lower chance of death than those not taking MHT. Khon Kaen University provided financial support for this review and had no involvement at any stage of the study. The authors have no conflicts of interest to declare. PROSPERO, CRD42021271882.

Tibetan medicine Liuwei Muxiang pills (LWMX pills) effectively protects mice from chronic non-atrophic gastritis

BackgroundChronic non-atrophic gastritis (CNG) is the most common type of chronic gastritis. If not actively treated, it may induce gastric cancer (GC). Western medicine is effective in CNG, but there are more adverse reactions after long-term medication, and it is easy to relapse after treatment, which affects patients’ health and life. Tibetan medicine Liuwei Muxiang Pills (LWMX pills) is a traditional Tibetan medicine compound, which has a unique curative effect in the treatment of gastric inflammation, especially chronic non-atrophic gastritis. However, the mechanisms of LWMX pills for treatment CNG still remain poor known. PurposeThe aim of this study was to evaluate the therapeutic intervention potential of Tibetan medicine LWMX pills on CNG and explore its potential mechanisms in mice models. MethodsThe mice models was established to evaluate the therapeutic effect of LWMX pills on CNG. The main components of LWMX pills were analyzed by GC-MS. HE staining, immunohistochemistry, proteomics and Western Blot were used to analyze the potential mechanism of LWMX pills for CNG treatment. ResultsIn the present study, LWMX pills containing costunolide, dehydrocostuslactone and antioxidants were found. IF results showed that the expression of ALDH1B1 in the control group was significantly lower than that in the model group in the gastric mucosa tissue, and the expression of ALDH1B1 was significantly lower in the 25 mg/ml LWMX Pills group (one month) and 25 mg/ml LWMX Pills group (two months) than in the model group. IHC revealed that model group samples expressed higher levels of Furin than 25 mg/ml LWMX Pills group samples, as evidenced by very strong staining of Furin in gastric mucosal cells. However, AMY2 staining in gastric mucosal cells did not differ significantly between the treated and control groups. the protein expression levels of these proteins were decreased in 25 mg/mL LWMX pills. Meanwhile, we found that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths).Western blotting showed that the protein expression levels of Furin, AMY2A, CPA3, ALDH1B1, Cam1, COXII, IL-6, IL-1β were decreased in 25 mg/mL LWMX pills. Meanwhile, that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths). Conclusion25mg/ml LWMX pill treatment for one month had better therapeutic effect on mice CNG. Further proteomic results showed that LWMX pills maintain gastric function by inhibiting inflammation and oxidative stress, and we also found that LWMX pills regulate the expression of proteins associated with cancer development (Amy2, Furin).

A Validation Study of Four Preoperative Surgical Planning Tools for Adult Spinal Deformity Surgery in Proximal Junctional Kyphosis and Clinical Outcomes.

Four guidelines have been suggested for optimal correction in adult spinal deformity surgery: Scoliosis Research Society (SRS)-Schwab classification, age-adjusted sagittal alignment goals, Global Alignment and Proportion (GAP) score, and the Roussouly algorithm. Whether these goals provide benefit in both proximal junctional kyphosis (PJK) reduction and clinical outcome improvement remains unclear. To validate 4 preoperative surgical planning tools in PJK development and clinical outcomes. We retrospectively reviewed patients who underwent ≥5-segment fusion including the sacrum for adult spinal deformity with a follow-up of ≥2-year. PJK development and clinical outcomes were compared among the groups separately using 4 surgical guidelines: SRS-Schwab pelvic incidence (PI)-lumbar lordosis (LL) modifier (Group 0, +, ++), age-adjusted PI-LL goal (undercorrection, matched correction, and overcorrection), GAP score (proportioned, moderately disproportioned, and severely disproportioned groups), and the Roussouly algorithm (restored and nonrestored groups). A total of 189 patients were included in this study. The mean age was 68.3 years, and there were 162 women (85.7%). There were no differences in the rate of PJK development and clinical outcomes among SRS-Schwab PI-LL modifier and GAP score groups. With the age-adjusted PI-LL goal, PJK developed significantly less frequently in the matched group compared with the under- and overcorrection groups. Clinical outcomes were significantly better in the matched group compared with the under- and overcorrection groups. With the Roussouly algorithm, PJK developed significantly less frequently in the restored group than in the nonrestored group. However, there were no differences in clinical outcomes between the 2 Roussouly groups. Correction according to the age-adjusted PI-LL goal and the restored Roussouly type was associated with reduced PJK development. However, differences in clinical outcomes were only observed in the age-adjusted PI-LL groups.