4-week Group Research Articles

Alteration of the gut microbiome and correlated metabolism in a rat model of long-term depression.

This study aims to investigate the composition and function of the gut microbiome in long-term depression using an 8-week chronic unpredictable mild stress (CUMS) rat model. Animals were sacrificed after either 4 weeks or 8 weeks under CUMS to mimic long-term depression in humans. The gut microbiome was analyzed to identify potential depression-related gut microbes, and the fecal metabolome was analyzed to detect their functional metabolites. The correlations between altered gut microbes and metabolites in the long-term depression rats were explored. The crucial metabolic pathways related to long-term depression were uncovered through enrichment analysis based on these gut microbes and metabolites. The microbial composition of long-term depression (8-week CUMS) showed decreased species richness indices and different profiles compared with the control group and the 4-week CUMS group, characterized by disturbance of Alistipes indistinctus, Bacteroides ovatus, and Alistipes senegalensis at the species level. Additionally, long-term depression was associated with disturbances in fecal metabolomics. D-pinitol was the only increased metabolite in the 8-week CUMS group among the top 10 differential metabolites, while the top 3 decreased metabolites in the long-term depression rats included indoxyl sulfate, trimethylaminen-oxide, and 3 alpha,7 alpha-dihydroxy-12-oxocholanoic acid. The disordered fecal metabolomics in the long-term depression rats mainly involved the biosynthesis of pantothenate, CoA, valine, leucine and isoleucine. Our findings suggest that the gut microbiome may participate in the long-term development of depression, and the mechanism may be related to the regulation of gut metabolism.

Comparison of the safety and effectiveness of different surgical timing for acute cholecystitis after percutaneous transhepatic gallbladder drainage: a systematic review and meta-analysis.

To compare the efficacy and safety of laparoscopic cholecystectomy (LC) in the treatment of acute cholecystitis (AC) at different time points after percutaneous transhepatic gallbladder drainage (PTGBD). PubMed, EMBASE, Cochrane Library, and Web of Science were searched from database inception to 1 May 2022. The last date of search was the May 30, 2022. The Newcastle-Ottawa scale (NOS) was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. A total of 12 studies and 4379 patients were analyzed. Compared with the < 2-week group, the ≥ 2-week group had shorter operation time, less intraoperative blood loss, shorter postoperative hospital stay, lower rate of conversion to laparotomy, and fewer complications. There was no statistical difference between the two groups regarding bile duct injury, bile leakage, and total cost. The evidence indicates that the ≥ 2-week group has the advantage in less intraoperative blood loss, minor tissue damage, quick recovery, and sound healing in treating AC. It can be seen that LC after 2weeks is safe and effective for AC patients who have already undergone PTGBD and is recommended, but further confirmation is needed in a larger sample of randomized controlled studies.

1,25-Dihydroxycholecalciferol down-regulates 3-mercaptopyruvate sulfur transferase and caspase-3 in rat model of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of liver morbidity and mortality and has multiple unclear pathogenic mechanisms. Vitamin D deficiency was associated with increased incidence and severity of NAFLD. Increased hepatic expression of 3-mercaptopyruvate sulfur transferase (MPST) and dysregulated hepatocyte apoptosis were involved in NAFLD pathogenesis. We aimed to explore the protective effect of 1,25-Dihydroxycholecalciferol (1,25-(OH)2 D3) against development of NAFLD and the possible underlying mechanisms, regarding hepatic MPST and caspase-3 expression. 60 male adult rats were divided into 4 and 12week fed groups; each was subdivided into control, high-fat diet (HFD), and HFD + VD. Serum levels of lipid profile parameters, liver enzymes, insulin, glucose, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and hepatic levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and reactive oxygen species (ROS) were measured. BMI and HOMA-IR were calculated, and liver tissues were processed for histopathological and immunohistochemical studies. The present study found that 1,25-(OH)2 D3 significantly decreased BMI, HOMA-IR, serum levels of glucose, insulin, liver enzymes, lipid profile parameters, CRP, TNF-α, hepatic levels of MDA, ROS, hepatic expression of MPST, TNF-α, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3; and significantly increased hepatic TAC in both HFD-fed groups. In conclusion: Administration of 1,25-(OH)2 D3 with HFD abolished the NAFLD changes associated with HFD in 4-week group, and markedly attenuated the changes in 12-week group. The anti-apoptotic effect via decrement of caspase-3 and MPST expression are novel mechanisms suggested to be implicated in the protective effect of 1,25-(OH)2 D3.

The effectiveness, acceptability, and sustainability of a 4-week DBT-informed group therapy in increasing psychological resilience for college students with mental health issues.

An adapted, time-limited dialectical behavior therapy (DBT) skills training group therapy can prove to be an evidence-based treatment that can easily fit the needs, demands, and limitations of University Counseling Centers to serve college students with mental disorders. The present naturalistic study investigated the effectiveness, acceptability, and sustainability of a 4-week DBT-informed group therapy in enhancing psychological resilience. Participants included 59 college students with heterogeneous mental health concerns. They attended weekly 1.5-hr DBT-informed, resilience-building group therapy for 4 weeks. Psychological resilience, mindfulness, emotional dysregulation, and overall distress were assessed at pretreatment and posttreatment, as well as at 1- and 3-month follow-ups. Findings showed increased psychological resilience among the participants at posttreatment and follow-ups, and provided preliminary evidence for the role of mindfulness as an important contributor to enhancing psychological resilience even after controlling for risk factors, treatment dosage, pregroup psychological resilience, and changes in emotion dysregulation and overall distress. A 4-week DBT-informed skills training group therapy can be utilized as a time-efficient, cost-effective, well-accepted preventative treatment with the potential longitudinal impact to boost psychological resilience for college students with mental health issues.

Cognitive behavioral stress management for parents: Prevention and reduction of parental burnout

ContextParental burnout increases the risk of deleterious consequences on parents’, couples’, and children's physical and mental health. MethodsThe current study (N = 134) aimed to assess the effectiveness of a Cognitive Behavioural Stress Management (CBSM) group programme in terms of parental burnout reduction. In total 67 parents attended the 8-week CBSM intervention groups, and another 67 parents were assigned to the waiting-list control group. We compared the effectiveness of the CBSM intervention with a waiting-list control group directly after the end of the programme and at three-months follow-up. ResultsThe results showed that compared to the control group the CBSM programme contributed to the reduction of parental burnout symptoms with statistically significant and small effect size. Moreover, the contrast analyses showed that the reduction in parental burnout severity was maintained at 3 month-follow-up. The reduction in parental burnout scores was mediated by the decrease in stress and the increase in unconditional self-kindness. ConclusionsThese results highlight the potential benefits of the CBSM programme for parental burnout prevention and reduction.

The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial

ObjectivesTo evaluate the immunogenicity of an extended interval regimen of BNT162b2 among healthy school-age children. MethodsA randomized-control trial conducted among healthy Thai children aged 5-11 years. Participants received two doses of BNT162b2 with an 8-week (extended dosing) vs 3-week interval. Immunogenicity was determined by neutralization test (NT) against the Omicron variant, surrogate virus NT (sVNT; BA.1, % inhibition), and pseudovirus NT (BA.2, the half-maximal inhibition dilution or ID50). The third dose was offered to participants who had sVNT <68% inhibition. The immunogenicity outcome was evaluated at 14 days after the second and third doses. ResultsDuring February to April 2022, 382 children with a median age (interquartile range) of 8.4 years (6.6-10.0) were enrolled. At 14 days, after two doses of BNT162b2, the geometric means of sVNT in 8-week vs 3-week interval groups were 49.6 (95% confidence interval [CI] 44.8-54.9) vs 16.5 (95% CI 13.0-20.9), with a geometric means ratio of 3.0 (95% CI 2.4-3.8). Among 102 participants who received the third dose at a median of 15 weeks from the second dose, the geometric means of sVNT increased to 73.3 (95% CI 69.0-77.8) and pseudovirus NT increased to 326 (95% CI 256-415). ConclusionThe extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.

Molecular Magnetic Resonance Imaging of Aneurysmal Inflammation Using a Redox Active Iron Complex.

Inflammation plays a key role in driving brain aneurysmal instability and rupture, but clinical tools to noninvasively differentiate between inflamed and stable aneurysms are lacking. We hypothesize that imaging oxidative changes in the aneurysmal microenvironment driven by myeloid inflammatory cells may represent a noninvasive biomarker to evaluate rupture risk. In this study, we performed initial evaluation of the oxidatively activated probe Fe-PyC3A as a tool for magnetic resonance imaging (MRI) of inflammation in a rabbit model of saccular aneurysm. The difference in longitudinal relaxivity ( r1 ) in reduced and oxidized states of Fe-PyC3A was measured in water and blood plasma phantoms at 3 T. A rabbit saccular aneurysm model was created by endovascular intervention/elastinolysis with subsequent decellularization in situ. Rabbits were imaged at 4 weeks (n = 4) or 12 weeks (n = 4) after aneurysmal induction, when luminal levels of inflammation reflected by the presence of myeloperoxidase positive cells are relatively high and low, respectively, using a 3 T clinical scanner. Both groups were imaged dynamically using a 2-dimensional T1-weighted fast field echo pulse MRI sequence before and up to 4 minutes postinjection of Fe-PyC3A. Dynamic imaging was then repeated after an injection of gadobutrol (0.1 mmol/kg) as negative control probe. Rabbits from the 12-week aneurysm group were also imaged before and 20 minutes and 3 hours after injection of Fe-PyC3A using an axial respiratory gated turbo-spin echo (TSE) pulse sequence with motion-sensitized driven equilibrium (MSDE) preparation. The MSDE/TSE imaging was repeated before, immediately after dynamic acquisition (20 minutes postinjection), and 3 hours after injection of gadobutrol. Aneurysmal enhancement ratios (ERs) were calculated by dividing the postinjection aneurysm versus skeletal muscle contrast ratio by the preinjection contrast ratio. After imaging, the aneurysms were excised and inflammatory infiltrate was characterized by fluorometric detection of myeloperoxidase activity and calprotectin immunostaining, respectively. In vitro relaxometry showed that oxidation of Fe-PyC3A by hydrogen peroxide resulted in a 15-fold increase of r1 at 3 T. Relaxometry in the presence of blood plasma showed no more than a 10% increase of r1 , indicating the absence of strong interaction of Fe-PyC3A with plasma proteins. Dynamic imaging with Fe-PyC3A generated little signal enhancement within the blood pool or adjacent muscle but did generate a transient increase in aneurysmal ER that was significantly greater 4 weeks versus 12 weeks after aneurysm induction (1.6 ± 0.30 vs 1.2 ± 0.03, P < 0.05). Dynamic imaging with gadobutrol generated strong aneurysmal enhancement, but also strong enhancement of the blood and muscle resulting in smaller relative ER change. In the 12-week group of rabbits, MSDE/TSE imaging showed that ER values measured immediately after dynamic MRI (20 minutes postinjection) were significantly higher ( P < 0.05) in the case of Fe-PyC3A (1.25 ± 0.06) than for gadobutrol injection (1.03 ± 0.03). Immunohistochemical corroboration using anticalprotectin antibody showed that leukocyte infiltration into the vessel walls and luminal thrombi was significantly higher in the 4-week group versus 12-week aneurysms (123 ± 37 vs 18 ± 7 cells/mm 2 , P < 0.05). Magnetic resonance imaging using Fe-PyC3A injection in dynamic or delayed acquisition modes was shown to generate a higher magnetic resonance signal enhancement in aneurysms that exhibit higher degree of inflammation. The results of our pilot experiments support further evaluation of MRI using Fe-PyC3A as a noninvasive marker of aneurysmal inflammation.

Research on 90-day subchronic toxicities of the ethanol extract from the cultivated Fritillaria Cirrhosa bulbs by oral administration in Sprague-Dawley rats

Fritillaria Cirrhosa bulbus (BFC) is a Chinese herbal medicine. In the present study, subchronic toxicities of the ethanol extract from cultivated Fritillaria Cirrhosa bulbus (ECBFC) were performed by oral daily administration in Sprague-Dawley rats. The subchronic toxicity test of ECBFC was conducted at doses of 0.34, 0.68, and 2.04 g/kg/day for 90 days (equivalent to the highest human clinical recommend dosage of 25, 50, and 150-fold) with a 4-week satellite group. No mortality or significant changes in behaviors, body weight and food consumption were observed during the experimental and recovery periods. According to the data from ematological analysis, biochemistry, organ coefficient and the results of histopathology, the ECBFC have toxicity to the spleen and liver at the highest (2.04 g/kg), medium (0.68 g/kg) dose and nephrotoxicity at the highest dose. Subchronic oral toxicity of ECBFC in SD rats (90 days) with NOAEL was 0.34 g/kg and LOAEL was 0.68 g/kg. In addition, the toxicity is gender neutral and reversible. The NOAEL value (0.34 g/kg) is 25-fold of the highest human clinical recommend dosage thus the ECBFC could be long-term used as Chinese patent medicine or functional food.

Schneiderian Membrane Collateral Damage Caused by Collagenated and Non-Collagenated Xenografts: A Histological Study in Rabbits

The Schneiderian membrane (SM) that is in contact with biomaterial granules may become thinner and eventually perforate. It has been shown that these events are related to the biomaterial used. Hence, the main aim of the present study was to compare the damaging effects of two xenografts with different resorbability rates on SM. The secondary aim was to evaluate the possible protection from damage offered by a collagen membrane placed adjacent to the SM and by inward displacement of the bone window with the SM during elevation. Thirty-six albino New Zealand rabbits underwent bilateral sinus elevation. One group of 18 animals received deproteinized bovine bone mineral (DBBM group) and the other received swine-collagenated corticocancellous bone (collagenated group). Moreover, in the DBBM group, the bone window was displaced inward during elevation in one sinus together with the SM. In the collagenated group, a collagen membrane was placed adjacent to the SM in one sinus. Six animals were assessed per period after 2, 4, and 8 weeks. The mean pristine mucosa width ranged between 67 µm and 113 µm, and none had a width of <40 µm. In the 2-week group, the elevated mucosa of the DBBM group presented 59 thinned sites and five perforations, while in the collagenated group, 14 thinned sites and one perforation were observed. Damage to SM decreased in number in the 4-week treatment group. In the 8-week group, the number of thinned sites in the DBBM group increased to 124, and the perforations to 8. In the collagenated group, 7 thinned sites and 1 small perforation were observed. More damage to the Schneiderian membrane was observed in the DBBM group than in the collagenated group. The presence of the inward bone window offered protection from damage to the Schneiderian membrane.

Stress CMR T1-mapping technique for assessment of coronary microvascular dysfunction in a rabbit model of type II diabetes mellitus: Validation against histopathologic changes.

Coronary microvascular dysfunction (CMD) is an early character of type 2 diabetes mellitus (T2DM), and is indicative of adverse events. The present study aimed to validate the performance of the stress T1 mapping technique on cardiac magnetic resonance (CMR) for identifying CMD from a histopathologic perspective and to establish the time course of CMD-related parameters in a rabbit model of T2DM. New Zealand white rabbits (n = 30) were randomly divided into a control (n = 8), T2DM 5-week (n = 6), T2DM 10-week (n = 9), and T2DM 15-week (n = 7) groups. The CMR protocol included rest and adenosine triphosphate (ATP) stress T1-mapping imaging using the 5b(20b)3b-modified look-locker inversion-recovery (MOLLI) schema to quantify stress T1 response (stress ΔT1), and first-pass perfusion CMR to quantify myocardial perfusion reserve index (MPRI). After the CMR imaging, myocardial tissue was subjected to hematoxylin-eosin staining to evaluate pathological changes, Masson trichrome staining to measure collagen volume fraction (CVF), and CD31 staining to measure microvascular density (MVD). The associations between CMR parameters and pathological findings were determined using Pearson correlation analysis. The stress ΔT1 values were 6.21 ± 0.59%, 4.88 ± 0.49%, 3.80 ± 0.40%, and 3.06 ± 0.54% in the control, T2DM 5-week, 10-week, and 15-week groups, respectively (p < 0.001) and were progressively weakened with longer duration of T2DM. Furthermore, a significant correlation was demonstrated between the stress ΔT1 vs. CVF and MVD (r = -0.562 and 0.886, respectively; p < 0.001). The stress T1 response correlated well with the histopathologic measures in T2DM rabbits, indicating that it may serve as a sensitive CMD-related indicator in early T2DM.

Broad Therapeutic Time Window for Driving Motor Recovery After TBI Using Activity-Dependent Stimulation

Background: After an acquired injury to the motor cortex, the ability to generate skilled movements is impaired, leading to long-term motor impairment and disability. While rehabilitative therapy can improve outcomes in some individuals, there are no treatments currently available that are able to fully restore lost function. Objective: We previously used activity-dependent stimulation (ADS), initiated immediately after an injury, to drive motor recovery. The objective of this study was to determine if delayed application of ADS would still lead to recovery and if the recovery would persist after treatment was stopped. Methods: Rats received a controlled cortical impact over primary motor cortex, microelectrode arrays were implanted in ipsilesional premotor and somatosensory areas, and a custom brain–machine interface was attached to perform the ADS. Stimulation was initiated either 1, 2, or 3 weeks after injury and delivered constantly over a 4-week period. An additional group was monitored for 8 weeks after terminating ADS to assess persistence of effect. Results were compared to rats receiving no stimulation. Results: ADS was delayed up to 3 weeks from injury onset and still resulted in significant motor recovery, with maximal recovery occurring in the 1-week delay group. The improvements in motor performance persisted for at least 8 weeks following the end of treatment. Conclusions: ADS is an effective method to treat motor impairments following acquired brain injury in rats. This study demonstrates the clinical relevance of this technique as it could be initiated in the post-acute period and could be explanted/ceased once recovery has occurred.

A pilot adaptive trial of text messages, mailed nicotine replacement therapy, and telephone coaching among primary care patients who smoke

IntroductionSequential multiple assignment randomized trials (SMART) inform the design of adaptive treatment interventions. We tested the feasibility of a SMART to deliver a stepped-care intervention among primary care patients who smoked daily. MethodsIn a 12-week pilot SMART (NCT04020718), we tested the feasibility of recruiting and retaining (>80 %) participants to an adaptive intervention starting with cessation text messages (SMS). The study randomly assigned participants (R1) to assessment of quit status, the tailoring variable, after either 4 or 8 weeks of SMS. The study offered continued SMS alone to those reporting abstinence. Those reporting smoking were randomized (R2) to SMS + mailed NRT or SMS + NRT + brief telephone coaching. ResultsDuring Jan–March and July–Aug 2020, we enrolled 35 patients (>18 years) from a primary care network in Massachusetts. Two (6 %) of 31 participants reported seven-day point prevalence abstinence at their tailoring variable assessment. The 29 participants who continued to smoke at 4 or 8 weeks were randomized (R2) to SMS + NRT (n = 16) or SMS + NRT + coaching (n = 13). Thirty of 35 participants (86 %) completed 12-weeks; 13 % (2/15) of those in 4-week group and 27 % (4/15) of those in 8-week group had CO < 6 ppm at 12-weeks (p = 0.65). Among 29 participants in R2, one was lost to follow-up, 19 % (3/16) of the SMS + NRT group had CO < 6 ppm vs. 17 % (2/12) of SMS + NRT + coaching (p = 1.00). Treatment satisfaction was high (93 %, 28 of 30 who completed 12-weeks). ConclusionsA SMART exploring a stepped-care adaptive intervention combining SMS, NRT, and coaching for primary care patients was feasible. Retention and satisfaction were high and quit rates were promising.

Comparison of the Effects of Skin Microneedling with Cupping Therapy and Microneedling Alone: An Experimental Study.

Microneedling promotes percutaneous collagen induction; cupping therapy creates negative pressure and leads to increased blood flow in the applied area. The addition of cupping therapy to microneedling is thought to contribute positively to microneedling's effects. This study was carried out to investigate the histologic effects of adding cupping therapy to microneedling. Thirty Wistar rats were divided into five groups, with six rats in each group. One control group and four experimental groups were formed, which are defined as follows: the control group; the single-session microneedling applied to the dorsal trunk group; the 15-minute cupping therapy added to the single-session microneedling group; the microneedling applied over a total of three sessions at 3-week intervals group; and the microneedling with cupping therapy applied over a total of three sessions at 3-week intervals group. Each animal was euthanized at the end of the fourth week following the last treatment, and skin samples were evaluated histologically with hematoxylin and eosin stain and type I and III collagen antibody immunostaining. The addition of cupping therapy to microneedling increased the thickness of the epidermis and dermis. A significant increase in type I collagen immunostaining and the type-I-to-type III collagen ratio was seen only in the single-session microneedling applied to the dorsal trunk group. Cupping therapy did not generate a significant difference in type I collagen immunostaining. No treatment was found to produce a significant increase in type III collagen immunostaining. Cupping therapy can be added to microneedling therapy and used to increase certain desired effects on skin. Microneedling is an easy and effective method to improve skin quality in clinical practice.

Managing patients with vitiligo by narrowband–ultraviolet-B and systemic vitamin D

Background The role of vitamin D in autoimmune disorders in general and in vitiligo in specific has drawn the attention of many authors recently. Topical vitamin D is known to help in restoring pigmentation in vitiligo. The effect of vitamin D deficiency in vitiligo is still not fully understood. Aim To examine the effect of correcting vitamin D deficiency on the clinical improvement of vitiligo. Setting and design A randomized clinical trial where patients attending the Dermatology Clinic and diagnosed with vitiligo were invited to participate. Patients and methods In all, 26 patients with vitiligo and vitamin D deficiency were recruited, and by simple randomization, they were assigned into one of the 12-week therapeutic groups: a combined therapy of narrowband–ultraviolet-B (NB–UVB) and oral vitamin D, and a monotherapy of oral vitamin D or a monotherapy of NB–UVB. Serum level of vitamin D was measured at three occasions; before and after treatment, and at onset of repigmentation. Statistical analysis: SPSS was used for statistical analysis; A P value of less than 0.05 was considered as statistically significant. Results Patients on a combined therapy of NB–UVB and oral vitamin D required the shortest time for repigmentation (2.4 weeks) compared with monotherapy of vitamin D (4.8 weeks) or phototherapy (6.4 weeks) (P&lt;0.05). However, the relationship between serum vitamin D level and onset of repigmentation was insignificant. Conclusions Replacement of vitamin D might positively influence the course of vitiligo management when combined with phototherapy. Further studies are required to confirm and identify the exact role vitamin D.

Ideal Duration of Pretreatment Using a Gelatin Hydrogel Nonwoven Fabric Prior to Subcutaneous Islet Transplantation

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment in comparison with intraportal islet transplantation. We herein investigated whether the duration of pretreatment using GHNF affected the outcome of subcutaneous islet transplantation. A silicone spacer with GHNF was implanted into the subcutaneous space of healthy mice at 2, 4, 6, or 8 weeks before transplantation, and then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, inflammatory mediators, and gene expression were evaluated. The 6-week group showed significantly better blood glucose changes than the other groups (P < 0.05). The cure rate of the 6-week group (60.0%) was the highest among the groups (2-week = 0%, 4-week = 50.0%, 8-week = 15.4%). The number of von Willebrand factor (vWF)–positive vessels in the 6-week group was significantly higher than in the other groups at pre-islet and post-islet transplantation (P < 0.01 [vs 2-and 4-week groups] and P < 0.05 [vs all other groups], respectively). Notably, this beneficial effect was also observed when GHNF was implanted into diabetic mice injected with streptozotocin 7 days before GHNF implantation. The positive rates for laminin, collagen III, and collagen IV increased as the duration of pretreatment became longer and were significantly higher in the 8-week group (P < 0.01). Inflammatory mediators, including interleukin (IL)-1b, granulocyte colony-stimulating factor (G-CSF), and interferon (IFN)-γ, were gradually downregulated according to the duration of GHNF pretreatment and re-elevated in the 8-week group. Taken together, the duration of GHNF pretreatment apparently had an impact on the outcomes of subcutaneous islet transplantation, and 6 weeks appeared to be the ideal duration. Islet graft revascularization, extracellular matrix compensation of the islet capsule, and the inflammatory status at the subcutaneous space would be crucial factors for successful subcutaneous islet transplantation.

The experiences of depressed pregnant women participating in a cognitive behavioral therapy program via video communication: an exploratory qualitative study.

This study explored the experiences of pregnant women with depressed mood participating ina group cognitive behavioral therapy (CBT) program using video communication, based on Beck's cognitive theory. The participants were six pregnant women out of 13 women who had participated in an 8-session group CBT program using video communication for women with depressed mood (EdinburghPostnatal Depression score of ≥9). Data were collected from February 20 through March 25, 2021. Indepth individual interviews were conducted through a video conferencing platform at 1 month post-baseline. Thematic analysis was done. Three themes, 10 subthemes, and 38 concepts were derived from experiences of participating inthe 4-week group CBT program (twice a week). The first theme, entitled "continuing realization" hadsubthemes of "a negative and instable self," "a selfish judgment that excludes others," and "a strong beliefin self-control." The second theme, entitled "attempt to change for restoration" had subthemes of "shift torational thinking," "freedom from suppressed beliefs," "tolerance of other people," and "courage for self-expression." The third theme, entitled "departure for a positive life," had subthemes of "emotional healing,""faith in oneself," and "reestablishing the criteria for happiness." Pregnant women with depressed mood expressed that continuing realizations and attemptsto change supported their transition toward a positive direction of healing. Thus, they were able to changetheir distorted thinking into rational thinking through CBT using video communication. These findingssupport the use of group CBT using video communication with pregnant women who have depressedmood.

Effects of different environmental intervention durations on the intestinal mucosal barrier and the brain-gut axis in rats with colorectal cancer

An enriched environment (EE) is a promising strategy for protecting the intestinal mucosal barrier and regulating the brain-gut axis, but the optimal EE intervention duration is unknown. Here, different EE intervention durations were applied to assess the optimal intervention duration in rats with colorectal cancer. We used a rat model of 1, 2-dimethylhydrazine-induced colorectal cancer. The rats were housed in an EE for 0, 2, 4, 8 weeks and 8-week blank group. The intestinal mucosa and serum TNF-α, IL-6, IL-10, ATP, CRF, and occludin levels and bacterial translocation (BT) were measured, and the intestinal mucosa morphology was evaluated. In 8 weeks, the effect of tumor on intestinal mucosal barrier was not obvious and the EE had a greater impact on it. Eight weeks of EE was more beneficial to the intestinal mucosal mechanical barrier than 2 or 4 weeks of intervention. A significant difference in BT was found between the 4- and 8-week groups. Overall, the analysis of inflammatory factor regulation revealed that the two blank groups exhibited the worst effect, and the intervention effect at 8 weeks was better than that at 2 and 4 weeks. CRF at 4 weeks was higher than that at 8-week blank group. The effect of 8-week intervention duration on the intestinal mucosal barrier was generally better than that of 2- and 4-week durations and intervention within 4 weeks can help to stabilize and promote the secretion of brain gut peptide, but the effect of different intervention durations on the brain-gut peptide levels was not obvious. In the future, we can further explore the molecular biological mechanism of the effect of different EE intervention durations on the intestinal mucosal barrier and analyze the effect of an EE on other brain-gut peptides.

Mechanisms of NO-Mediated Protein S-Nitrosylation in the Lens-Induced Myopia

Myopia is a chronic ocular disease, emerging as the most common type of refractive error. This study intends to preliminarily explore the roles of protein S-nitrosylation of nitric oxide (NO) in the regulation of myopia by detecting the expression of neuronal nitric oxide synthase (nNOS) and downstream S-nitrosylation, using the animal model of lens-induced myopia (LIM) in mice. The 3-week-old C57BL/6 J mice were divided into three groups: group I, lens-induced 0-week group (take eyeballs at the age of 3 weeks); group II, self-control eyes of experimental group (take eyeballs at the age of 7 weeks); and group III, lens-induced 4-week group (take eyeballs at the age of 7 weeks). The diopter and axial length of each group were measured by streak retinoscopes and optical coherence tomography (OCT) before and after model establishment. The protein expressions and locations of nNOS and S-nitrosylated proteins (PSNOs) were measured by western blot and immunofluorescence staining. Site-specific proteomic for protein S-nitrolysation was used to detect the existence and location of S-nitrosylation proteins in the retina of myopic and nonmyopic mice. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and motif enrichment analyses were performed. The differential sites were analyzed by GO, KEGG, and motif. Irreversible biotinylation procedure combined with protein purification and western blot was used to detect the protein expression of α-enolase (ENO1), a key player in the hypoxia-related signal pathway. The expressions of nNOS and PSNOs were significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. A total of 595 S-nitrosylated proteins, 709 S-nitrosylated peptides, and 708 S-nitrosylated sites were identified by site-specific S-nitrolysation proteomics in the retina of myopic and control eyes. A total of 19 differentiation loci were screened, of which 13 sites were downregulated and 6 sites were upregulated in experimental eyes compared with the self-control group. Specifically, the expression of SNO-ENO1 was significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. LIM induces the decrease of nNOS and PSNO protein levels in the retina of myopic mice. NO-mediated nonclassical protein S-nitrosylation modification may play an important role in the regulation of lens-induced myopia. ENO1 may be a key factor in the regulation of S-nitrosylation modification of myopia.

Comparison of hypoxia-induced pulmonary hypertension rat models caused by different hypoxia protocols

Background and aim: Pulmonary hypertension (PH) is a serious and even fatal disorder with limited treatment strategies. The hypoxia-induced pulmonary hypertension (HPH) rat model is commonly used in this field. While the HPH rat model has strong predictability and repeatability, the model is a chronic model, making it time-consuming, costly, and complicated and limiting the progress of the experiments. Currently, there is no uniform international standard for the HPH model. Our study aimed to find a relatively effective and efficient HPH modeling protocol. Methods: We established HPH rat models with different total hypoxia periods and different daily hypoxia times, and assessed different hypoxia modeling modes in multiple dimensions, such as haemodynamics, right ventricular (RV) hypertrophy, pulmonary arterial remodeling, muscularization, inflammation, and collagen deposition. Results: Longer daily hypoxia time resulted in higher mean pulmonary arterial pressure (mPAP)/right ventricular systolic pressure (RVSP) and more obvious RV hypertrophy, as well as more severe pulmonary arterial remodeling and muscularization, regardless of the total period of hypoxia (3- or 4-week). Moreover, pulmonary perivascular macrophages and collagen deposition showed daily hypoxia time-dependent increases, both in 3- and 4-week hypoxia groups. Conclusion: Our findings showed that the 3-week continuous hypoxia mode was a relatively efficient way to reduce the time needed to induce significant disease phenotypes, which offered methodological evidence for future studies in building HPH models.

LIMPER trials: immediate mobilisation versus 2-week cast immobilisation after distal radius fracture treated with volar locking plate – a study protocol for a prospective, randomised, controlled trial

IntroductionOpen reduction and internal fixation with volar locking plate has become the most common fixation method in the treatment of unstable distal radius fracture (DRF). There is, however, no consensus...