Drug-treated Groups Research Articles

Effects of Du Meridian Moxibustion Combined with Mild Moxibustion on Female Pelvic Floor Myofascial Pain Syndrome: A Retrospective Cohort Study.

This study aimed to investigate the efficacy and safety of moxibustion in the treatment of pelvic floor myofascial pain syndrome. A total of 80 women with pelvic floor myofascial pain syndrome (cold coagulation and blood stasis type) were included in this retrospective study and divided into a moxibustion group and a drug treatment group. Patients who received Celebrex oral analgesia, health education, and lifestyle improvement were included in the drug treatment group. The patients that received Du meridian moxibustion combined with mild moxibustion, health education, and lifestyle improvement were included in the moxibustion group. The comparison of pelvic pain, the TCM clinical symptom score, and the curative effect was made between the two groups before treatment and after 1-3 weeks of treatment, respectively. An intragroup comparison showed a stepwise decrease in the VAS score and the TCM clinical symptom score of the two groups during the treatment. An intergroup comparison revealed that the VAS score of the moxibustion group was lower than that of the drug treatment group, while TCM clinical symptoms and clinical efficacy significantly improved in the moxibustion group compared to those in the drug treatment group (P < 0.05). Du meridian moxibustion combined with mild moxibustion alleviates pelvic floor myofascial pain syndrome, thus helping improve women's quality of life and providing patients with a more effective and safer treatment plan.

Microglia Regulating Neuronal Apoptosis Via Alpha7 Nicotinic Acetylcholine Receptor in HIV-Associated Neurocognitive Disorders

Background: Microglia, the innate immune cells of the central nervous system (CNS), originate from erythromyeloid progenitor cells in the embryonic yolk sac. As the innate immune cells of the CNS, microglia play an important role in innate immunity, neurogenesis, and brain tissue repair by activating the alpha7 nicotinic acetylcholine receptor (α7nAChR). They are the key target cells for HIV-1 infection in the CNS and have been shown to produce a chronic inflammatory response in the brain which underlies HIV-associated neurocognitive disorders (HAND). Apart from the microglial neuroinflammation, recent studies have reported that activated microglia could induce neuronal apoptosis through the release of neurotoxic factors (e.g., ROS and NLRP3 inflammasome) in HAND. In addition, α7nAChR was significantly up-regulated in the striatum which is the most serious part of neuron apoptosis in gp120 transgenic mice brains. However, the underlying mechanism of neuronal cell apoptosis by gp120-activated microglia remains unclear. Here, this study aimed to explore the mechanism by which HIV-1 gp120-activated microglia induce neuronal apoptosis. Materials and methods: The expression of α7nAChR was examined by immunohistochemistry in the brain of HIV-1 LAV gp120 transgenic (Tg) mice (C57BL/6J background, 12-month-old). Methyllycaconitine (MLA, specific α7nAChR agonists) and Nicotine (NT, specific α7nAChR antagonists) were used to evaluate the effect of α7nAChR on apoptosis induced by gp120. Immortalized microglial cells (BV2) were incubated for 24 hours with gp120, NT, and gp120+NT, respectively, with or without preincubation with MLA for 15 minutes to obtain their supernatants. Next, the neuronal cells (SH-SY5Y) were treated with the same as BV2 or with collected BV2 culture supernatants. The apoptosis effect of SH-SY5Y and the level of ROS in the BV2 culture supernatants were assessed via quantitative analysis of flow cytometry. Comparisons between supernatant groups and drug groups were conducted to evaluate the effects of the SH-SY5Y apoptosis induced by microglia. Western blotting of microglia cell lysates was employed for the analysis of cellular signaling pathways. Student's t-tests and ANOVA were applied to determine statistical significance. Results: The expression of α7nAChR in HIV-1 gp120 transgenic mice was significantly upregulated (P < 0.001). The effect of apoptosis was more significant in microglia culture supernatants groups compared to that in drug-treated groups (P < 0.001). Neuronal activity was not changed in the NT group or MLA group than in the control, but HIV-1 gp120 could increase the number of apoptotic neurons (P < 0.01). Significant neuronal apoptosis was observed when treated with BV2 supernatants from the group treated by combining the gp120 with NT (P < 0.001), and this effect was in turn inhibited by MLA (P < 0.001). These results suggested that gp120-activated microglia might induce neuronal apoptosis invitro owing to gp120 upregulating α7nAChR. In addition, the ROS level in microglia was significantly upregulated following gp120 exposure (P < 0.001), and this effect could be enhanced by NT (P < 0.001). Notably, there was a positive correlation between the levels of ROS in microglia culture supernatants and the levels of neuronal apoptosis treated in the same supernatants. This positive relevance indicated that microglia might induce neuronal apoptosis by producing excessive ROS. The expressions of p53, OMI, and caspase-3 significantly upregulated following gp120 exposure with the down-regulate expression of XIAP (P < 0.001). And this effect could be enhanced by NT (P < 0.001). The results of western blotting indicated that gp120 and NT can up-regulate the ROS to activate p53 by α7nAChR, which could lead to an increased OMI and decreased XIAP levels. (P < 0.001). Conclusions: Microglia may play a critical role in regulating neuronal apoptosis in HAND. HIV-1 gp120 and NT could increase the generation of ROS through α7nAChR in microglia, which leads to neuronal apoptosis. Moreover, our results showed that the combined action of NT and gp120 may upregulate p53 and Omi / HtrA2 protein expression, and the downregulation of XIAP protein may significantly activate the level of caspase-3. (Acknowledgements:Corresponding author: Hong Cao, gzhcao@smu.edu.cn; National Natural Science Foundation of China, No. 82172259 to H.C.) Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of the anti-RANKL monoclonal antibody in rheumatoid arthritis rats.

In this study, we aimed to investigate the therapeutic effect of anti-receptor activator of nuclear factor kappa-κB ligand (RANKL) monoclonal antibodies R748-1-1-1, R748-1-1-2 and R748-1-1-3 on rheumatoid arthritis (RA) in a rat model. Gene cloning, hybridoma technology, affinity purification, enzyme-linked immunosorbent assay, general observation, hematoxylin-eosin staining, X-ray, and many other experimental techniques were used in this study. Improved collagen-induced arthritis (CIA) modeling was successfully constructed. The RANKL gene was cloned and the anti-RANKL monoclonal antibody was prepared. Following treatment with the anti-RANKL monoclonal antibody, the soft tissue swelling of the hind paws, the joint thickening, the narrowed joint gap, and the blurred edge of the bone joint were improved. The pathological changes such as synovial hyperplasia of fibrous tissue, cartilage and bone destruction were significantly decreased in the anti-RANKL monoclonal antibody-treated CIA group. Compared to the normal control group and phosphate buffer saline (PBS)-treated CIA group, the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) in antibody-treated CIA group, positive drug-treated CIA group, and IgG-treated CIA group were decreased (p<0.05). The anti-RANKL monoclonal antibody can promote the therapeutic effect of RA rats, indicating that the anti-RANKL monoclonal antibody has a certain potential value and may be beneficial to the further study of the mechanism of RA treatment.

Nursing experience of caring for a case undergoing hemodialysis for the first time due to drug abuse

&lt;p&gt;本文探討一位因長期藥物濫用致腎衰竭，需接受血液透析治療，於住院期間及出院後透析時，引發生理、心理和社會衝擊之護理經驗。筆者於2019年01月08日至2019年03月30日，運用羅氏適應模式，藉由直接護理、身體評估、觀察、傾聽、會談及查閱病歷等技巧收集相關資料，確立健康問題有：體液容積過量、潛在危險性感染及因應能力失常等。運用接納關懷建立良好護病關係，給予個別性、整體性護理措施。教導水分控制及導管照護知識，提升自我照顧能力，並照會社工師跨團隊照護，協助案父申請長照2.0服務，及急難補助金、就業服務站、民間戒毒團體等資源，使其接受血液透析造成的生活改變，以正向態度面對未來生活；建議定期舉辦跨領域、跨專業討論，如：每月舉辦跨團隊討論會，邀請民間及政府相關人員到院演講，使護理人員運用不同專業，提供適切護理照顧，期望藉由此經驗，為日後臨床照護之參考。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;This article discusses the nursing experience of a patient who required hemodialysis treatment for kidney failure caused by long-term drug abuse and the associated physical, psychological, and social shocks during hospitalization and dialysis after hospital discharge. From January 8, 2019 to March 30, 2019, Roy&amp;rsquo;s adaptation model of nursing was used to collect relevant information through techniques of direct care, physical assessment, observation, listening, interviews, and medical record review. Fluid overload, potentially dangerous infections, and response malfunction were observed in the patient. Meanwhile, acceptance therapy was used to establish a good nurse-patient relationship and to provide individualized as well as holistic care measures. The patient was provided knowledge on water control and catheter care to improve his self-care ability; social workers were also available for cross-team care. Furthermore, the patient was provided assistance in applying for long-term care 2.0 services, as well as for accessing resources from emergency subsidies, employment service stations, and private drug treatment groups to enable him to accept changes in his life caused by hemodialysis and to help him maintain a positive attitude toward life. It is recommended to schedule multi-disciplinary and cross-professional discussions, such as monthly cross-team discussions inviting private and government personnel to deliver lectures, on a regular basis to help the nursing staff make the best use of the different healthcare professionals to provide appropriate nursing care. The nursing experience reported here is expected to serve as a reference for future clinical care.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Effects of reduced portosystemic flow on hepatic myelopathy in patients with cirrhosis after TIPS

Objective: To investigate the impact of a reduced portacaval shunt on hepatic myelopathy (HM) in patients with cirrhosis after a transjugular intrahepatic portosystemic shunt (TIPS). Methods: Patients who developed HM after receiving TIPS at the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to June 2018 were retrospectively analyzed. HM severity was quantified by clinical spasticity index (CSI) and Fugl-Meyer Assessment (FMA) of the lower extremity. Clinical manifestations were combined with grades Ⅰ-Ⅳ. HM patients were divided into drug treatment (group A) and flow restriction group (group B) according to different treatment methods. The changes in CSI and FMA of the lower extremity after treatment were statistically analyzed in the two groups. P<0.05 was considered a statistically significant difference. Results: A total of 421 cases of cirrhosis who underwent TIPS were enrolled. Among them, 30 developed HM, with 22 in group A and 8 in group B. The incidence of HM after TIPS surgery was about 7.13%. After treatment, CSI was gradually increased and FMA of lower extremity was gradually decreased in group A, while vice-versa in group B. CSI in the two groups were differed significantly at 6, 12, 18, and 24 months after treatment (P<0.05), while the difference in FMA of the lower extremity was statistically significant at 12, 18, and 24 months after treatment (P<0.05). CSI was decreased and FMA of lower extremity was increased after treatment in patients with group A HM grade I. CSI, and FMA of lower extremity changes were statistically significant (P<0.05) when compared with patients with HM grades Ⅱ-Ⅳ. The incidence of hepatic encephalopathy was significantly lower in group B than that in group A (P=0.034), but there was no statistically significant difference between the two groups in the incidence of gastrointestinal bleeding, ascites, infection, MELD score and mortality. Conclusion: A reduced portacaval shunt can improve HM in patients with liver cirrhosis after TIPS, and drug therapy alone is effective for patients with early HM grade I.

Metoprolol Mitigates Ischemic Heart Remodeling and Fibrosis by Increasing the Expression of AKAP5 in Ischemic Heart.

The harm of heart failure mainly causes patients to develop dyspnea, fatigue, fluid retention, and other symptoms, which impair patients' activity tolerance and lead to a dramatic decrease in patients' quality of life. The purpose of this study was to verify whether metoprolol regulates AKAP5 expression and test the role of AKAP5 postinjury in mitigating cardiac infarction-associated tissue remodeling and fibrosis. Sprague-Dawley (SD) rats underwent coronary artery ligation (CAL), which was followed immediately with metoprolol daily. And western blot and coimmunoprecipitation experiments were performed to detect the expression of related proteins in the sham-operated group, model group, and drug-treated group. HW/BW ratio and cardiac expression of COL1 and COL3 were increased in rats following CAL compared with shams. Treatment with metoprolol postinjury was associated with a decrease in HW/BW ratio and COL1/COL3 expression compared to uncontrolled rats. CAL resulted in decreased cardiac AKAP5 expression compared to the control group, while metoprolol treatment restored levels compared to baseline shams. Cardiac expression levels of NFATc3/p-NFATc3 and GATA4 were modest at baseline and increased with injury, whereas metoprolol suppressed gene expression to below injury-associated changes. Immunoprecipitation indicated that AKAP5 could bind and regulate PP2B. In summary, we know that metoprolol alleviates ischemic cardiac remodeling and fibrosis, and the mechanism of alleviating remodeling may improve cardiac AKAP5 expression and AKAP5-PP2B interaction.

A study on the safety and therapeutic effect of Xiaoyaosan on depressive disorder related dry eye disease in a murine animal model

ABSTRACT This study was done to observe the safety and effect of Xiaoyaosan (XYS) on the stimulated depressive disorder (DD) related dry eye disease (DED) in mice. Normal control (NC) group, Vehicle group, and drug treatment groups, including Sertraline Hydrochloride (SH), XYS low-dose (XYS-LD), medium-dose (XYS-MD), and high-dose (XYS-HD), were established. The drug quality of XYS was assessed by high-performance liquid chromatography (HPLC). XYS toxicity in kidney and liver was assessed with Hematoxylin & Eosin (H&E) staining. Serum enzyme-linked immunosorbent assay (ELISA) and body weights were used to evaluate the depression status of mice. Tear production, corneal sensitivity, Oregon Green Dye (OGD) staining, and corneal confocal microscopy were used to assess ocular surface changes. H&E staining was also used to assess pathological cornea and lacrimal gland changes. HPLC results showed that XYS complied with Chinese drug quality standards. The drug treatment groups observed no drug toxicity reactions in the liver and kidney. SH and XYS groups improved DD-related serological indices as compared with Vehicle. Body weight was enhanced in mice with XYS groups compared to Vehicle and SH. Mice with XYS treatments showed increased tear production and corneal sensitivity, decreased corneal OGD staining scores, improved morphology, and decreased inflammatory cell infiltration in the cornea and lacrimal gland. In conclusion, XYS had no drug toxicity, improved serological indices, and ocular surface pathological changes in DD-related DED mice. XYS is safe and may have a therapeutic effect on DD-related DED.

Different treatment methods and efficacy analysis of otitis media with effusion in children with different hearing loss

Objective:To explore and analyze the treatment methods and effects of otitis media with effusion in children with different hearing loss. Methods:Clinical data of 318 children （556 ears） with otitis media with effusion（OME）admitted to Department of Otorhinolaryngology Head and Neck Surgery, Children Hospital Affiliated to Zhejiang University of Medicine from January 2020 to December 2021 were collected. Different treatment methods were selected according to the degree of hearing loss, combined with course of disease and the characteristics of effusion in tympanic cavity. They were divided into drug treatment group: critical hearing loss and mild hearing loss, and the course of disease was less than 3 months; myringotomy group: mild hearing loss and course of disease ≥3 months or moderate and severe hearing loss and course of disease<3 months, tympanic effusion was rarefied liquid; tympanostomy tube insertion group: mild hearing loss and course of disease ≥3 months, or moderate and severe hearing loss group and course of disease<3 months, tympanic effusion is sticky or jelly liquid, and moderate and severe hearing loss group and course of disease ≥3 months. 95% of children with adenoid hypertrophy or tonsillar hypertrophy and adenoid hypertrophy were diagnosed as obstructive sleep apnea hypopnea syndrome（OSA） and underwent endoscopic adenoidectomy or tonsillectomy and adenoidectomy. The curative effect and recurrence of different treatment groups were compared. Results:The drug treatment group and myringotomy group were followed up in 1, 3 and 6 monthes after operation. The tympanostomy tube insertion was followed up every three months after operation, with an average of one year. The patients were followed up in 1, 3 and 6 monthes after taking the tube off. The effective rates of drug treatment group, myringotomy group and tympanostomy tube insertion group were 95.6%, 89.6% and 90.9% respectively. The three groups recurred in 6, 4 and 5 ears respectively, and the difference was not statistically significant. Tympanic membrane perforation was left in 4 ears, 3 ears in tympanic tube group and 1 ear in myringotomy group. Multivariate Logistic regression analysis showed that allergic rhinitis（OR=0.073, 95%CI: 0.013-0.401, P=0.003） was the factor influencing the therapeutic effect of OME. Conclusion:the treatment of OME in children should not only be combined with course of disease, but also combined with different hearing loss and the characteristics of effusion in tympanic cavity. Different treatment methods can get the same effect, with low recurrence rate, small damage and satisfactory safety. Allergic rhinitis affects the therapeutic effect of OME.

Effect and mechanism of Huangqi Shengmai Decoction in treatment of joint rat model of fatigue and myocardial injury

This study aims to investigate the effects and the underlying mechanism of Huangqi Shengmai Decoction(HQSMD) in the treatment of fatigue and myocardial injury in a joint rat model. Wistar rats were assigned into 4 groups: sham, model, diltiazem hydrochloride(positive control), and HQSMD. The joint model of fatigue and myocardial injury was established by 14-day exhausted swimming followed by high ligation of the left anterior descending coronary artery. The rats in the sham group underwent a sham operation without coronary artery ligation or swimming. Since the fourth day after the ligation, swimming was continued in the model group and the drug-treated groups for the following 4 weeks. Meanwhile, the rats in the positive control group and the HQSMD group were respectively administrated intragastrically with diltiazem hydrochloride(20 mg·kg~(-1)·d~(-1)) and HQSMD(0.95 g·kg~(-1)·d~(-1)) for 4 weeks, while the shams and the models were given the same volume of normal saline. The left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), grip strength, and myocardial pathophysiological changes were measured to evaluate the anti-fatigue and cardioprotective effects of HQSMD. The protein levels of PTEN-induced putative kinase 1(PINK1) and parkin in the myocardium were measured by Western blot to preliminarily elucidate the mechanism of HQSMD in ameliorating myocardial injury by suppressing mitochondrial autophagy. Compared with the shams, the models showed weakened heart function(LVEF and LVFS, P&lt;0.01), decreased grasping ability(P&lt;0.05), elevated blood urea nitrogen(BUN) and aldosterone(ALD) levels(P&lt;0.01), aggravated myocardial fibrosis and connective tissue hyperplasia(P&lt;0.01), and up-regulated protein levels of PINK1(P&lt;0.01) and parkin(P&lt;0.05). Four-week treatment with HQSMD increased the LVEF and LVFS levels(P&lt;0.01), enhanced the grip strength(P&lt;0.01), reduced the serum levels of BUN(P&lt;0.01) and ALD(P&lt;0.05), alleviated the pathological injury and fibrosis in the myocardium(P&lt;0.01), and down-regulated the protein levels of PINK1(P&lt;0.01) and parkin(P&lt;0.05) in heart tissue. The results demonstrate that HQSMD may alleviate myocardial fibrosis and protect myocardium by suppressing the excessive mitochondrial auto-phagic activity and reducing the excessively elevated ALD level, thereby ameliorating fatigue and myocardial injury.

The Neuroprotective Role of Acorus calamus in Developmental and Histopathological Changes in Autism-Induced Wistar Rats.

Introduction Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and a tremendous increase in the incidence of autism poses challenges in identifying the different treatment modalities. Since the defined etiology, pathophysiology, and treatment of autism are unavailable, translational research is being done by creating animal models of autism. This study aimed to assess the effects of Acorus calamus on developmental and histopathological changes in autism-induced Wistar rats. Materials and methods A rat model of autism was created by administering sodium valproate on the 12th day of pregnancy, and rat pups of this group were considered autism-induced. Rat pups of pregnant rats who had received normal saline on the 12th day of pregnancy were consideredgroup I (negative control group). Neural reflexes were assessed in early postnatal days (PND) to confirm the development of autism. Autism-induced rat pups were divided into the following two groups: group II, autism (positive control group), and group III, autism + A. calamus (drug-treated group). On the 21st postnatal day (PND), group III was given an ethanolic extract of A. calamus (200 mg/kg), and group I and group II were given normal saline orally for 15 days. After 15 days of drug exposure, at 36thPND, the rats were sacrificed, and brain tissue was collected for histopathological analysis. Results When compared to the negative control group, autism-induced rat pups showed delayed appearance of neurological reflexes. Neurodegenerative changes were well appreciated in group II (autism-induced rats) than in group III (autism + A. calamus). In the histomorphometric analysis, group II showed a significant reduction in the number of neurons in the frontal cortex and Purkinje cells in the cerebellum. However, when compared to group II, group III (autism treated with A. calamus) did not show significant alteration. Conclusion Valproate exposure at mid-pregnancy creates autism by disturbing neural structures among rat pups. This was clinically represented as the delayed appearance of neural reflexes. Acorus calamus in the early postnatal period protects rat pups' brain morphology against autism pathology.

Effect and Mechanism of siRNAs Targeting IL-1β/TNF-α Combined with BMSCs Transplantation in Ameliorating Rheumatoid Arthritis in Rats.

Simple SummaryThe study aimed to explore the effect and potential mechanisms of siRNAs targeting IL-1β/TNF-α combined with BMSCs transplantation in ameliorating RA in rats. Collagen-induced arthritis model rats were randomly treated with IL-1β/TNF-α siRNA, BMSCs and IL-1β/TNF-α siRNA + BMSCs for 28 days. Compared with PBS group, BMSCs, siRNA, siRNA + BMSCs treatment groups showed significant lower toe swelling value, the immobility time, the spleen index, serum contents of IL-1β and TNF-α. In addition, the DR-X results showed that the knee carton surface tended to smoothing without bone hyperplasia, suggesting that these three treatments were all able to successfully ameliorate RA symptoms. In addition, compared with PBS group, the protein expression of p-NF-κB-p65 was significantly reduced in the knee of siRNA + BMSCs rats. BMSCs labeled with BrdU were also found in the knee of rats. Moreover, the mRNA expression of IL-1β, TNF-α and NF-κB-P65 in spleen tissue of siRNA + BMSCs rats were all significantly inhibited. Our results demonstrated that IL-1β/TNF-α siRNA, BMSCs and IL-1β/TNF-α siRNA + BMSCs were able to ameliorate RA inflammation by inhibiting the activation of NF-κB signaling pathways and reducing the erosion of articular cartilage, and IL-1β/TNF-α siRNA + BMSCs treatment showed synergism effects. Our study provides a new idea for gene and stem cell therapy for RA.Background: Rheumatoid arthritis (RA) is an autoimmune disease. Bone marrow mesenchymal stem cells (BMSCs) have multilineage differentiation and anti-inflammatory potential, and small interfering RNAs (siRNAs) can inhibit the target gene expression, which make them suitable for ameliorating RA. The current study was aimed to explore the effect and potential mechanisms of siRNAs targeting IL-1β/TNF-α combined with BMSCs transplantation in ameliorating RA in rats. Methods: Collagen-induced arthritis (CIA) model rats were randomly divided into five groups: PBS (Model control group), methotrexate (Positive drug treatment group), BMSCs (BMSCs transplantation group), siRNA (IL-1β/TNF-α siRNAs injection group), siRNA + BMSCs (Both IL-1β/TNF-α siRNAs injection and BMSCs transplantation group). After treatment for 0, 7, 14, 21, 28 days, the ameliorating effect was comprehensively assessed through results of the body weight, toe swelling value, the immobility time of forced swimming, the serum concentrations of IL-1β and TNF-α, knee joint DR-X imaging and pathological analysis as well as of IL-1β, TNF-α and NF-κB mRNA expression in spleen tissue. Furthermore, the potential underlying mechanism involving the NF-κB signaling pathways was also explored. Results: Compared with the PBS group, BMSCs, siRNA, siRNA + BMSCs treatment groups showed significant lower toe swelling value, immobility time, spleen index, serum contents of IL-1β and TNF-α. In addition, the DR-X results showed that the knee carton surface tended to smoothing without bone hyperplasia, suggesting that these three treatments were all able to successfully ameliorate RA symptoms. In addition, compared with the PBS group, the protein expression of p-NF-κB-p65 was significantly reduced in the knees of siRNA + BMSCs rats. BMSCs labeled with BrdU were also found in the knees of rats. Moreover, the mRNA expression of IL-1β, TNF-α and NF-κB-P65 in spleen tissue of siRNA + BMSCs rats were all significantly inhibited. Conclusions: Our results demonstrated for the first time that siRNA + BMSCs was able to ameliorate RA inflammation by inhibiting the activation of NF-κB signaling pathways and reducing the erosion of articular cartilage, and siRNA + BMSCs treatment showed synergism effects in helping ameliorating the inflammation and cartilage repair of RA rats. Therefore, the results of our present study provide a new idea for gene and stem cell therapy for RA.

Oroxylum indicum stem bark extract exerts antitumor potential against Ehrlich’s ascites carcinoma in Swiss albino mice

Introduction and Aim: Constant efforts are exerted to explore unique bioactive principles from natural sources that possess more effective and specific antineoplastic activities. In the present study, we aimed to evaluate the antitumor activity of stem bark extract of Oroxylum indicum in mice bearing Ehrlich ascites carcinoma (EAC). Materials and Methods: Ninety female Swiss albino mice were categorized into fifteen groups (n=6). The animals were inoculated with 1x106 EAC cells. Tumor control animals received sterile water once daily for 10 consecutive days. Positive control group was injected with Cisplatin (CP) (one dose – 3.5 mg/kg body weight). The treatment groups were administered with O. indicum (OI) stem bark ethanol extract once daily with 50mg/kg, 200mg/kg and 400mg/kg body weight for eleven consecutive days. The blood parameters and serum hepatic enzymes activity was determined. The percentage increase in weight, the median survival time, the increase in median life span was calculated. The cytotoxic effect of CP and OI extract was determined. Results: There was significant reduction in the white blood cells count in OI and CP treatment group compared to increased level in EAC control group. The RBC count and Hemoglobin level which was significantly decreased (p&lt;0.05) in the tumour mice, was enhanced in the drug treatment groups. The EAC control group showed significant increase in tumour cell count (p&lt;0.05) whereas, treatment of EAC tumor bearing mice with OI and CP significantly increased the non-viable tumor cell count (p&lt;0.05). Conclusion: OI stem bark ethanol extract reduced the toxic implications of Ehrlich ascites carcinoma, reverted the haematological and biochemical changes induced by tumour. These results call for additional research on isolating and identifying the responsible bioactive elements in order to clarify the underlying processes of the anticancer impact.

Astragalus membranaceus and Salvia miltiorrhiza Ameliorate Hypertensive Renal Damage through lncRNA-mRNA Coexpression Network.

lncRNAs and mRNA are closely associated with hypertensive renal damage, and Astragalus membranaceus and Salvia miltiorrhiza (AS) have a therapeutic effect; however, the mechanism of AS to ameliorate hypertensive renal damage through the co-expression network of lncRNA-mRNA was unclear. In this study, we investigated the role of AS regulated the coexpression network of lncRNA-mRNA in improving hypertensive renal damage. Sixteen 24-week old spontaneous hypertensive rats (SHRs) were randomly divided into model group (M) and drug intervention group (AS, 5.9 g/kg), 8 Wistar Kyoto rats (WKY) of the same age as normal group (N). The treatment of rats was 4 weeks. Detecting the change of blood pressure, renal pathology and renal function related indicators, and lncRNA and mRNA sequencing and joint analysis was performed on the kidney. AS reduced blood pressure; decreased urine NAG, urine mALB, serum CysC, and IL-6; and improved renal pathology compared with group M. Simultaneously, AS reversed the disordered expression of 178 differential expression (DE) mRNAs and 237 DE-lncRNAs in SHRs, and their joint analysis showed that 13 DE-mRNAs and 32 DE-lncRNAs were coexpressed. Further analysis of 13 coexpressed DE-mRNAs showed negative regulation of blood pressure and fatty acid beta-oxidation was highly enriched in GO pathways, PPAR signaling pathway was highly enriched in KEGG pathways, and the verification related to these pathways was also highly consistent with the sequence. AS can alleviate hypertensive renal damage through the coexpression network of lncRNA-mRNA, of which coexpressed 13 DE-mRNAs and 32 DE-lncRNAs were the important targets, and the pathway negative regulation of blood pressure, fatty acid beta-oxidation, and PPAR signaling pathway play a major regulatory role.

Different Involvement of ASIC and TRPA1 in Facial and Hindpaw Allodynia in Nitroglycerin-Induced Peripheral Hypersensitivities in Mice.

The pathophysiological mechanism underlying migraine-associated peripheral hypersensitivity remains unclear. Acid-sensing ion channels (ASICs) and transient receptor potential ankyrin 1 (TRPA1) are known to be causative pathogenic factors of mechanical and cold allodynia, respectively. Here, we sought to investigate their involvement in cold and mechanical allodynia of the face and hindpaws, respectively, in a mouse model of repetitive nitroglycerin (NTG)-induced migraine. NTG (10 mg/kg) was administered to the mice every other day for 9 days, followed 90 min later by HC-030031 (a TRPA1 blocker) or amiloride (a non-selective ASIC blocker). Mechanical or cold sensitivity of the hindpaw and facial regions was quantified using von-Frey filaments or acetone solution, respectively. Immunohistochemistry revealed that c-Fos expression was significantly increased in the trigeminal nucleus caudalis region but not in the spinal cord. Amiloride treatment only reduced NTG-induced hindpaw mechanical allodynia, whereas HC-030031 treatment only improved facial cold allodynia. Interestingly, the number of c-Fos positive cells decreased to a similar level in each drug treatment group. These findings demonstrate that facial cold allodynia and hindpaw mechanical allodynia are differentially mediated by activation of TRPA1 and ASIC, respectively, in mice with repetitive NTG-induced hypersensitivity.

Therapeutic effect of autologous bone marrow cells injected into the liver under the guidance of B‑ultrasound in the treatment of HBV‑related decompensated liver cirrhosis.

The 5-year mortality rates associated with decompensated liver cirrhosis (DLC) can reach 50%, which suggests that this condition poses a serious health risk. In previous studies conducted by our group, autologous bone marrow nucleated cells (ABMNCs) were used to treat HIV-positive patients with DLC through the right omental vein; however, trauma and poor compliance were encountered. In the present study, the percutaneous liver approach to inject ABMNCs under the guidance of B-ultrasound was employed for the treatment of DLC. A total of 108 patients with DLC were retrospectively divided into the routine drug treatment group (control group; 30 cases), the right omental vein infusion of ABMNCs group (observation group 1; 38 cases) and the B-ultrasound-guided liver injection of ABMNCs group (observation group 2; 40 cases). After treatment, the liver synthesis (prothrombin time, albumin and ascites) and secretion functions (total bilirubin) in observation groups 1 and 2 were significantly improved compared with those of the control group (P<0.01) and the bone marrow function was also significantly improved compared with that of the control group (P<0.01). While, the bone marrow function (white blood cell, platelet, and hemoglobin) in observation group 1 was significantly improved compared with that of observation group 2 at the end of treatment (P<0.01). After a 1-year follow-up, the case fatality rate was 2.5% (1/40) in observation group 2, which was significantly lower than the 20% fatality rate (6/30) recorded in the control group (P<0.05). The injection of ABMNCs into the liver under the guidance of B-ultrasound was significantly better than conventional drug therapy in treating DLC. This approach has obvious advantages such as no hospitalization, minimal trauma, rapid recovery and good compliance, all of which make it worthy of application in primary hospitals.

Drug-related problem characterization and the solved status associated factor analysis in a pharmacist-managed anticoagulation clinic.

Drug-related problems (DRPs) in a pharmacist-managed anticoagulation clinic (AC) have not been extensively studied. We aimed to characterize the DRPs in a pharmacist-managed AC, identify the factors associated with the solved status of DRPs, and analyze the secondary outcomes, including the safety and efficacy of AC service. The patients receiving services at a pharmacist-managed AC in a medical center for the first time from March 2019 to August 2020 were reviewed retrospectively. The DRPs were retrieved from a self-developed Intelligent AC Service System and classified according to the Pharmaceutical Care Network Europe Foundation v9.0 classification system. Logistic regression models were performed to identify the potential factors associated with the solved status of DRPs. A total of 78 direct oral anticoagulant (DOAC) and 34 warfarin users were included. The major types of DRPs identified at the initial service were adverse drug events (ADEs) (68.4%) and untreated symptoms or indications (14.8%) in the DOAC group, and ADEs (51.6%) and suboptimal effect of drug treatment (38.7%) in the warfarin group. The rates of totally solved DRPs were 56.8% and 51.6% in the DOAC and warfarin groups, respectively. According to the multivariable analysis, receiving AC services 3 times or more in 180 days (OR 3.11, 95% CI 1.30–7.44) was associated with the totally solved status of DRPs in the DOAC group, but no relevant factor was identified in the warfarin group. The secondary outcomes showed that DOAC users demonstrated fewer thromboembolism events, major bleeding, and bleeding-related hospitalizations after AC services, whereas the warfarin users increased percentage time in therapeutic range (TTR% 55.0% vs. 74.6%, P = 0.006) after AC services. These findings may be utilized to develop DOAC and warfarin AC services.

ANTIOXIDANT ACTIVITY TEST AND EFFECT OF ETHANOL EXTRACT OF NUSA INDA PUTIH (Mussaenda pubescens) AGAINST CREATININE, URIC ACID AND UREUM LEVELS IN WHITE RATS (Rattus novergicus)

The purpose of this study was to examine the antioxidant activity and the effect of the extract of Nusa Indah Putih (Mussaenda pubescens) on creatinine, uric acid and urea levels in white rats (Rattus novergicus). The study design, the treatment group was divided into 5 groups. The control group (P0), the ethylene glycol group (P1), the kidney drug treatment group (P2), the Nusa Indah Putih ethanol extract group at a dose of 100 mg/kgBW (P3), and the Nusa Indah Putih ethanol extract group at a dose of 200 mg/kgBW (P4 ). Nusa Indah Putih extract has strong antioxidant activity with IC50 value of 78.27 ppm and AAI value of 1.277. Nusa Indah Putih extract was effective in lowering creatinine, uric acid and urea levels in experimental animals.

Pharmaceutical Agents for Contractile-Metabolic Dysfunction After Volumetric Muscle Loss.

Volumetric muscle loss (VML) injuries represent a majority of military service member casualties and are common in civilian populations following blunt and/or penetrating traumas. Characterized as a skeletal muscle injury with permanent functional impairments, there is currently no standard for rehabilitation, leading to lifelong disability. Toward developing rehabilitative strategies, previous research demonstrates that the remaining muscle after a VML injury lacks similar levels of plasticity or adaptability as healthy, uninjured skeletal muscle. This may be due, in part, to impaired innervation and vascularization of the remaining muscle, as well as disrupted molecular signaling cascades commonly associated with muscle adaptation. The primary objective of this study was to assess the ability of four pharmacological agents with a strong record of modulating muscle contractile and metabolic function to improve functional deficits in a murine model of VML injury. Male C57BL/6 mice underwent a 15% multimuscle VML injury of the posterior hindlimb and were randomized into drug treatment groups (formoterol [FOR], 5-aminoimidazole-4-carboxamide riboside [AICAR], pioglitazone [PIO], or sildenafil [SIL]) or untreated VML group. At the end of 60 days, the injury model was first validated by comparison to age-matched injury-naive mice. Untreated VML mice had 22% less gastrocnemius muscle mass, 36% less peak-isometric torque, and 27% less maximal mitochondrial oxygen consumption rate compared to uninjured mice (p < 0.01). Experimental drug groups were, then, compared to VML untreated, and there was minimal evidence of efficacy for AICAR, PIO, or SIL in improving contractile and metabolic functional outcomes. However, FOR-treated VML mice had 18% greater peak isometric torque (p < 0.01) and permeabilized muscle fibers had 36% greater State III mitochondrial oxygen consumption rate (p < 0.01) compared to VML untreated mice, suggesting an overall improvement in muscle condition. There was minimal evidence that these benefits came from greater mitochondrial biogenesis and/or mitochondrial complex protein content, but could be due to greater enzyme activity levels for complex I and complex II. These findings suggest that FOR treatment is candidate to pair with a rehabilitative approach to maximize functional improvements in VML-injured muscle. Impact statement Volumetric muscle loss (VML) injuries result in deficiencies in strength and mobility, which have a severe impact on patient quality of life. Despite breakthroughs in tissue engineering, there are currently no treatments available that can restore function to the affected limb. Our data show that treatment of VML injuries with clinically available and FDA-approved formoterol (FOR), a beta-agonist, significantly improves strength and metabolism of VML-injured muscle. FOR is therefore a promising candidate for combined therapeutic approaches (i.e., regenerative rehabilitation) such as pairing FOR with structured rehabilitation or cell-seeded biomaterials as it may provide greater functional improvements than either strategy alone.

Therapeutic Effects and Mechanism of Liraglutide in Rats with Type 2 Diabetes and Metabolic-associated Fatty Liver Disease.

SREBP-1c/Insig/SCAP acts as a lipid de novo synthesis pathway, and its factors are highly expressed in the endoplasmic reticulum. At present, this pathway has become a research hotspot in the development of metabolic-associated fatty liver disease. However, there are few studies on how various factors in this pathway change after endoplasmic reticulum stress; in particular, the role of the insulin-inducing gene-1 (Insig-1) has not been elucidated in detail. The aim of the study was to investigate whether liraglutide has a therapeutic effect on rats with T2DM and MAFLD, and to further study its possible mechanism. Rats in the control group and modeling group were fed with normal diet and high-sugar and high-fat diet, respectively. After one month, the mice in the modeling group were injected with 35mg/kg STZ intraperitoneally to establish the model of type 2 diabetes mellitus. T2DM and MAFLD rats were randomly divided into three groups: model group, low-dose liraglutide group, and high-dose liraglutide group. Fasting blood glucose, fasting insulin, blood lipid profile, alanine aminotransferase, and aspartate aminotransferase were measured at the end of 8th week. Paraffin sections were obtained from the same part of the liver of rats in each group and observed by electron microscope after HE staining. Western blot was used to detect the expression of endoplasmic reticulum stress index (GRP78) and negative feedback index of lipid synthesis (Insig-1) in each group. Liver tissue from the drug intervention groups demonstrated a decrease in lipid droplet vacuoles, and the hepatocytes were arranged neatly again. While the expression of GRP78 rose, that of Insig-1 declined. There were differences observed with different doses of liraglutide; the higher the dose was, the more obvious the effect. No such changes were observed in T2DM and MAFLD rats after injection of saline. In this study, we show that liraglutide may have a therapeutic effect on rats with T2DM and MAFLD by reducing endoplasmic reticulum stress in the liver and increasing the expression of Insig-1.

High counting of circulating tumor cells in blood is not directly related to metastasis.

Circulating tumor cells (CTCs) in blood flow have been believed as an essential biomarker of cancer. The technologies of in vitro and in vivo CTC enrichment and detection suggest although CTCs might play a role of "seed" in metastasis, only the minority of CTCs, probably in the form of CTC clusters, hold the potential to develop a tumor in organs. The detected amount of CTCs might be solely an indicator of tumor burden. To provide new insights into this argument, we take advantage of a safe drug to tune the pacemaker activity of a mouse tumor model to increase the heart rate for a period of time every day during the tumor development. We detect the CTCs in vivo by fast line scanning of a confocal microscope when the heart rate returns to the baseline and find the average CTC amount is significantly elevated in the drug-treated group but the metastases are even less than that of control. Our results imply the detected CTC counts in blood might not be directly related to metastasis.