This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Objective To explore the adverse drug event signal of piperacillin-tazobactam(TZP)and promote rational and safe use of drugs in clinic.Methods The proportional unbalance method was used to mine the signals of all TZP adverse events(ADE)reports from the inception of FDA adverse event reporting system(FAERS)to March 2024.The basic situation of the the reported cases and the relevant information of adverse reactions were analyzed.Results A total of 20 620 513 ADE reports were obtained for the main suspected drugs,and 6 489 ADE reports were reported for TZP as the main suspected drug.543 ADE signals were mined,involving 25 system organ classifications(SOC).43 ADE signals were detected by secondary screening,and 17 ADE signals were new ADR signals.The top 5 ADE signals involved in SOC classification were skin and subcutaneous tissue disorders,general disorders and administration site reactions,various examinations,infections and infectious disease,and blood and lymphatic system disorders.The top 5 preferred terms for ADE signal number were rash,pyrexia,acute kidney injury,pruritus and thrombocytopenia.Penicillins had several ADE signals on blood and lymphatic system diseases.TZP led to thrombocytopenia with the largest number of cases,and oxacillin led to agranulocytosis with the highest proportional reporting ratio.The median treatment course of TZP induced leukopenia was 11.00 days,and the median accumulated dose was 148.50 g.The median treatment course of TZP induced agranulocytosis was 14.00 days,and the median accumulated dose was 216.00 g.The median treatment course of TZP induced thrombocytopenia was 7.00 days,and the median accumulated dose was 87.00 g.Conclusion The adverse reactions related to skin and subcutaneous tissue diseases should be paid close attention to during medication,which may be more common than those of gastrointestinal diseases.When large doses or long courses of TZP are clinically used,close attention should be paid to the adverse reactions related to blood and lymphatic system disorders to avoid serious ADE.

Objective To observe the effect of Zuogui Jiangtang Shuxin Decoction on diabetes atherosclerosis in ApoE-/-mice induced by streptozotocin combined with high-fat diet;To explore its mechanism of diabetes atherosclerosis by regulating intestinal flora and glucose and lipid metabolism.Methods Diabetic atherosclerosis model was constructed by intraperitoneal streptozotocin 40 mg/kg combined with a high-fat diet in 8-week-old male ApoE-/-mice,which were randomly divided into model group,Zuogui Jiangtang Shuxin Decoction group and metformin group,with 5 mice in each group,another 5 C57BL/6 mice were set as the blank control group.Zuogui Jiangtang Shuxin Decoction group were given Zuogui Jiangtang Shuxin Decoction 28.86 g/kg for gavage,the metformin group was given metformin 0.065 g/kg for gavage,and the model group and blank control group were given same volume of distilled water for gavage for consecutive 8 weeks.Fasting blood glucose(FBG)was detected,automatic biochemical analyzer was used to detect serum triglycerides(TG)and total cholesterol(TC)contents,morphology of pancreas,aorta and colonic tissue were observed by HE staining.Intestinal contents were collected to detect the changes of intestinal flora by sequencing with 16S rRNA amplicon.Results Compared with the blank control group,the FBG,TG,TC content in the model group significantly increased(P<0.01);the pancreatic lobules had an unclear lobe structure and a large number of atrophied glandular follicles;the intima-media of the aorta was hyperplastic,exhibiting visible atheromatous plaques and lumen stenosis;the structure of colonic tissue was unclear,and the intestinal mucosa in certain parts was vesiculously eroded,accompanied by inflammatory cells infiltration.Compared with the model group,the FBG,TG,TC content in Zuogui Jiangtang Shuxin Decoction group and metformin group significantly decreased(P<0.01);the pancreatic tissue structure was improved,atherosclerotic plaque and lipid deposition reduced,the colonic mucosal epithelium repaired,and inflammatory cell infiltration reduced.Alpha and Beta diversity analyses showed that the groups of samples were able to separate significantly,with the total number and abundance of intestinal flora species being lower in the model group.Compared with the blank control group,the relative abundance of the model group increased in Firmicutes,Desulfobacterota,Clostridia,Desulfovibrionia and Lachnospiraceae,decreased in Bacteroidota,Bacteroidia,Muribaculaceae and Muribaculaceaes(P<0.01).Compared with the model group,the relative abundance of Zuogui Jiangtang Shuxin Decoction group decreased in Firmicutes,Desulfobacterota,Clostridia,Desulfovibrionia and Lachnospiraceae,and increased in Bacteroidota,Bacteroidia,Muribaculaceae and Muribaculaceaes(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Shuxin Decoction can regulate the intestinal microecology,thereby inhibiting the formation of diabetic atherosclerotic plaque.The mechanism may be related to its regulation of intestinal flora structure,improvement of glucose and lipid metabolism,protection of pancreatic tissues,and repair of the intestinal mucosal barrier.

Objective:To investigate the epidemiology, risk factors and biochemical indexes of nutritional status in children and adolescents aged 2~18 years in Southwest China.Methods:Children attending routine health checkups at the Children′s Hospital of Chongqing Medical University between April 2017 and March 2021 were enrolled in this study.Nutritional status was defined based on BMI cut-off values, and statistically analyzed based on gender, region and age.Its risk factors were analyzed by multivariate Logistic regression.Results:A total of 22 609 cases were recruited and the overall prevalence of wasting, overweight and obesity was 5.87%, 9.81% and 10.50%, respectively.The prevalence of obesity and wasting in boys was higher than that in girls ( χ2=24.79, 12.39, all P<0.05), and the prevalence of overweight in boys was lower than that in girls( χ2=4.32, P<0.05). The prevalence of overweight among boys in urban regions was higher than that in rural regions( χ2=4.68, P<0.05). Compared in three age groups, boys aged 12~18 years had the highest prevalence of obesity( χ2=12.49, P<0.01), while girls had the lowest prevalence of wasting( χ2=6.18, P<0.05). Compared with boys, girls had a lower risk of obesity and wasting ( OR=0.80, 95% CI: 0.73~0.87), ( OR=0.80, 95% CI: 0.71~0.90). Compared to children aged 12~18 years, children aged 2~<6 years had a lower risk of obesity ( OR=0.55, 95% CI: 0.46~0.67), while children aged 6~<12 years had a higher risk of wasting ( OR=1.70, 95% CI: 1.25~2.33). Significant differences were reported in ALT, AST, ALP, UA, UN, CRE, TG, TC, HDL-C and LDL-C levels in obese children (all P<0.05). Conclusion:The nutritional status of children and adolescents in Southwest China is comparable to that at the national level.The prevalence of obesity and wasting is associated with gender and age.Obese children are more likely to have biochemical abnormalities.

OBJECTIVE: To investigate the effect of body mass index (BMI) on the short-term effectiveness of high tibial osteotomy (HTO) in the treatment of varus knee arthritis. METHODS: The clinical data of 84 patients (84 knees) with varus knee arthritis treated with HTO between May 2016 and August 2020 were retrospectively analyzed. According to BMI, the patients were divided into normal group (32 patients in group A, BMI<25 kg/m ²), overweight group (27 patients in group B, BMI>30 kg/m ²), and obese group (25 patients in group C, BMI>30 kg/m ²). The BMI of groups A, B, and C were (23.35±0.89), (26.65±1.03), and (32.05±1.47) kg/m ², respectively. There was no significant difference ( P>0.05) in gender, age, surgical side, disease duration, and preoperative Hospital for Special Surgery (HSS) score, visual analogue scale (VAS) score, knee range of motion, and hip-knee-ankle angle (HKA) between groups. The operation time, intraoperative dominant blood loss, and the decrease of hemoglobin on the 3rd day after operation were recorded and compared between groups. The improvement of knee joint function and pain status were evaluated by knee joint HSS score, knee range of motion, and VAS score before and after operation, and measuring the HKA of patients on X-ray film. During the follow-up, the X-ray films of the knee joint were reexamined to observe the position of the internal fixator and the healing of osteotomy. RESULTS: All patients completed the operation successfully and were followed up 8-40 months (mean, 19.3 months). There was no significant difference in follow-up time, operation time, intraoperative dominant blood loss, and the decrease of hemoglobin on the 3rd day after operation between groups ( P>0.05). No operative complications such as severe vascular or nerve injury occurred. After operation, deep venous thrombosis of lower extremities occurred in 1 case in groups A and B respectively, and fat liquefaction of surgical incision occurred in 2 cases in group C. There was no significant difference in the incidence of perioperative complications between groups (3.1% vs. 3.7% vs. 8.0%) ( P=0.689). During the follow-up, there was no bone nonunion, plate fracture or loosening. At last follow-up, HSS score, VAS score, knee range of motion, and HKA significantly improved in the 3 groups when compared with those before operation ( P<0.05), but there was no significant difference in the differences of the above indexes between groups before and after operation ( P>0.05). CONCLUSION BMI does not affect the short-term effectiveness of HTO in the treatment of varus knee arthritis. HTO can be selected for overweight and obese patients after standard medical treatment is ineffective.
Humans ; Osteoarthritis, Knee/surgery* ; Body Mass Index ; Overweight ; Retrospective Studies ; Treatment Outcome ; Knee Joint/surgery* ; Obesity/complications* ; Osteotomy ; Blood Loss, Surgical

ObjectiveTo investigate the mechanism of Huangqi Guizhi Wuwutang （HQGZWWT） in the treatment of diabetic peripheral neuropathy （DPN） in MKR mice via regulating endoplasmic reticulum （ER） stress. MethodThirty-two 8-week-old MKR mice （half were male and half were female） were fed with a high-fat diet for four weeks， and then 1% streptozotocin （STZ） was injected intraperitoneally for five days. After the blood glucose was stabilized， the mice were housed in the cage covered with ice bags for another one hour stimulation per day for four weeks. Mice with fasting blood glucose （FBG） value ≥11.1 mmol·L^-1 were randomly divided into model group ， Huangqi Guizhi Wuwutang in original dosage group （30 g·kg^-1·d^-1）， Huangqi Guizhi Wuwutang in formula dosage group （6.25 g·kg^-1·d^-1）， and positive drug group （mecobalamin tablets， 0.17 mg·kg^-1·d^-1）. Another eight MKR mice of the same age were set as blank group and eight FVB mice were normal group. After four weeks of intragastric administration in each group， the change in FBG was tested， and hematoxylin and eosin （HE） staining and transmission electron microscope were used for observing the morphology of sciatic nerve tissue. In addition， the expression of c-Jun N-terminal kinase （JNK）， phosphorylated c-Jun N-terminal kinase （p-JNK） and inositol requiring enzyme 1α （IRE1α） proteins was determined by immunohistochemical test and Western blot （WB）. ResultCompared with the conditions in the normal group and blank group， the time of paw withdrawal， paw licking and tail flick in the model group was shortened （P<0.01）， and the conduction velocity of sciatic nerve was decreased （P<0.01）. Compared with the conditions in the model group， the behavioral and functional indicators were improved by HQGZWWT （P<0.05，P<0.01）. The immunohistochemical test revealed the JNK expression was elevated in the model group compared with the conditions in the normal group and blank group （P<0.05）， while that was lowered by HQGZWWT compared with the condition in the model group （P<0.05）. However， there was no difference among the treatment groups. According to the WB， the expression of IRE1α and p-JNK in the model group was enhanced compared with the conditions in the normal group and blank group （P<0.05，P<0.01）， while that was decreased by HQGZWWT compared with the condition in the model group （P<0.05，P<0.01）. No difference was observed between the HQGZWWTO and HQGZWWTF groups. ConclusionHQGZWWT can improve the neurophysiological function and pathological damage of sciatic nerve， which may be related to its delaying the ER stress response of sciatic nerve.

Objective:To investigate the cognition and willingness of nursing staff to Internet plus nursing service, and analyze the related factors that affect their participation in Internet plus nursing service.Methods:From April to May 2019, 150 nurses from three hospitals in Weifang were investigated by questionnaire and key person interview. Descriptive analysis and binary logistic regression analysis were used to analyze the intention of nursing staff to participate in Internet plus nursing service. The interview mode was used to analyze the appropriate mode of Internet plus nursing service from the perspective of nursing staff.Results:142 valid questionnaires were obtained, of which 137(96.5%)indicated willingness to provide Internet plus nursing services, and 135(95.1%) realized the necessity of the service. Education, marriage, nurses′judgment on the necessity of the service and their own subjective judgment of their competence were the factors affecting nurses′ participation in the Internet plus nursing service.Conclusions:Multiple factors affect the choice of nursing staff′s behavior in Internet plus nursing service.From the perspective of nursing staff, the Internet plus nursing service mode needs joint efforts from many aspects.

Objective:To study the performance of the elastic fixation with our self-designed Tightrope system for inferior tibiofibular syndesmosis (ITFS) diastasis.Methods:In this self-control study, 6 specimens of normal cadaveric ankle were used as a normal ITFS group while the models of the ITFS diastasis were constructed as a group of ITFS diastasis. On the models of ITFS diastasis, elastic fixation with transverse Tightrope system (transverse fixation group) or binding Tightrope system (binding fixation group) was applied. The reduction and stability of ITFS were compared between transverse fixation and binding fixation for ITFS diastasis in terms of ITFS parameters on X-Ray[tibiofibular clear space (TFCS) and medial clear space (MCS)] and on CT[inferior tibiofibular anterior clear space (ITFACS), inferior tibiofibular middle clear space (ITFMCS), inferior tibiofibular posterior clear space (ITFPCS), anterior inferior tibiofibular interval (AITFI) and fibular rotation (θfib)].Results:The transverse fixation with Tightrope system for ITFS diastasis on the models led to iatrogenic injury to the fibular and the ITFS interosseous ligaments and to the perforating peroneal artery, and malreduction as well while the binding fixation with Tightrope system caused no injury to the anterior or the posterior ITFS ligament or the superior peroneal retinaculum but fine reduction as well. In comparisons of TFCS, ankle MCS, ITFACS, ITFMCS and AITFI between the 4 groups, normal ITFS group

Objective:To investigate the prevenlence of insomnia on workers and related influcecing factors in chip manufacturing industry.Methods:By using cluster sampling method, 2 251 workers in chip manufacturing industry were selected as study subjects. The simple Job Demand-Control model Questionnnaire (JDC) , Effort-Reword Imbalance (ERI) Questionnnaire and Insomnia Symptoms Scale were used to evaluate JDC occupational stress, ERI occupational stress and insomnia symptoms respectively.Results:22.6% (509/2251) workers were found high level of insomnia. The risk factors of insomnia symptoms were high score of effort and overcommitment ( P< 0.05) . The risk of insomnia symptoms in high effort was 1.689 times that of low score (95% CI: 1.334-2.138) . The risk of insomnia symptoms in high overcommitment was 1.835 times that of low score (95% CI: 1.461-2.305) . The protective factors for insomnia symptoms were women, monthly income of more than 3000 yuan, college dregree or above, high work control and high reward ( P<0.05) . Conclusion:The high scores of effort and overcommitment are the risk factors for insomnia symptoms of employees in manufacture electronic devices. Enterprises should take comprehensive measures to pay attention to the occurrence of insomnia symptoms among employees with high score of effort and overcommitment.