ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

OBJECTIVE: To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.

Objective To construct a management program for upper limb lymphedema prevention in postopera-tive breast cancer patients and to evaluate its effectiveness.Methods The first draft of the upper limb lymphede-ma prevention and management protocol for postoperative breast cancer patients was constructed on the basis of ev-idence summaries and qualitative interviews,and 2 rounds of correspondence were conducted in December 2022.Using the convenience sampling method,patients undergoing surgery for malignant tumours in the breast surgery de-partment of a tertiary-level hospital in Zhengzhou City were selected as the study subjects,and 58 patients admitted from January to March 2023 were included in the experimental group according to the time of their first visit.57 patients admitted from July to December 2022 were included in the control group and were given routine care.The rates of lymphedema occurrence,upper limb function score and patients'adherence to lymphedema prevention be-haviours after 1,3,and 6 months of intervention were compared between the 2 groups.Results The valid ques-tionnaire recovery rates of the 2 rounds of expert correspondence were 92.59％and 100％,and the authority coeffi-cients of the experts were 0.940 and 0.950,and the Kendall's harmony coefficients were 0.228 and 0.254,respec-tively(P＜0.00 1).The coefficients of variation of the 2nd round of correspondence were 0.07～0.24.The final draft of the programme included 5 first-level entries,12 second-level entries,and 32 third-level entries.During the appli-cation of the programme,a total of 5 cases were dislodged,and 55 cases were finally included in each of the ex-perimental and control groups.The results of repeated measures ANOVA showed that there was an interaction ef-feet between the upper limb function scores and lymphedema prevention behavior compliance scores before inter-vention and at 1,3,and 6 months after discharge between the 2 groups(P＜0.05).Simple effects analysis showed that at 1,3,and 6 months after discharge,the upper limb function score and lymphedema prevention behavior com-pliance score of the experimental group were better than those of the control group,and the differences were sta-tistically significant(P＜0.05).At 6 months post-intervention,the difference in the occurrence of lymphedema was statistically significant when comparing the 2 groups(P=0.032).Adverse events such as subcutaneous bruising and falls did not occur in either group.Conclusion The upper limb lymphoedema prevention and management pro-gramme for postoperative breast cancer patients constructed in this study is scientific,feasible and safe,and can ef-fectively reduce the incidence of lymphoedema in patients and improve their quality of life.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

Objective:To evaluate nutritional status and to analyse risk factors of acute exacerbation of chronic obstructive pulmonary disease (COPD) in the elderly.Methods:Data of elderly hospitalized patients with COPD mainly from 5 grade A, class 3 hospitals (Beijing Hospital, Shanghai Huadong Hospital, Tianjin Nankai hospital, the Second Affiliated Hospital of Medical College of Zhejiang University, Guangzhou First People′s Hospital) from January 2012 to December 2020 were retrospectively analyzed. According to the global initiative for chronic obstructive lung disease criteria (GOLD), elderly COPD patients were divided into acute exacerbation group and stable group. The differences in age, gender, medical history, anthropometry, laboratory examination, nutritional support, results of nutritional risk screening 2002 (NRS2002) and global leadership initiative on malnutrition (GLIM) were compared between the two groups after admission, and the risk factors of acute exacerbation of COPD in the elderly were analyzed by multivariate Logistic regression.Results:A total of 339 elderly patients with COPD aged 65-100 years were included in this study, including 177 cases (52.21%) in acute exacerbation stage. The detection rate of malnutrition in acute exacerbation stage was higher than that in stable stage (51.98% vs 41.98%, P<0.05). The weight, body mass index and grip strength of patients in the acute exacerbation stage were significantly lower than those in the stable period [(55.47±8.42) vs (60.63±9.30) kg, (20.52±4.25) vs (22.39±4.57) kg/m 2, (12.32±4.21) vs (16.59±2.97) kg] (all P<0.05). Spearman correlation analysis showed that the acute exacerbation of elderly patients with COPD was positively correlated with malnutrition ( r=0.443, P<0.001), and negatively correlated with body weight, body mass index and calf circumference ( r=-0.200, -0.214, -0.135, all P<0.05). Multiple Logistic regression analysis showed that acute exacerbation in elderly patients with COPD was only related to malnutrition ( OR=7.799, 95% CI: 4.466-13.622, P<0.001). Conclusions:The incidence of malnutrition in acute exacerbation stage of elderly COPD patients is high. Malnutrition is independently related to acute exacerbation of COPD.

OBJECTIVE：To evaluate the economy of pe rospirone in the treatment of schizophrenia ，to provide guidance for clinically proper use of medications more cost-effectively ，and related health decision-making . METHODS ：A short-term decision tree model was constructed from the perspective of medical insurance payer to calculate the cost and health outcomes of different treatment plans considering major adverse events including extrapyramidal reaction ，weight gain ，diabetes，hyperlipidemia. The cost-utility of perospirone were compared with quetiapine ，aripiprazole and olanzapine respectively ，using QALYs as the measure of health outcomes ，3 times GDP per capita as the willingness-to-pay threshold ；probability sensitivity analysis was performed. RESULTS：The results of base-case analysis showed that the cost of perospirone （6 688.25 yuan）was lower than those of quetiapine （9 887.45 yuan），aripiprazole（13 284.65 yuan）and olanzapine （15 332.80 yuan）. The utility of perospirone （0.79 QALYs）was better than those of quetiapine （0.76 QALYs），aripiprazole（0.77 QALYs）and olanzapine （0.75 QALYs）. Compared with quetiapine ， aripiprazole and olanzapine ，peropirone had lower cost and higher health outcome ，which indicated that strong dominance favors perospirone over the other 3 drugs. The results of sensitivity analysis were consistent with those of base-case analysis. CONCLUSIONS：Perospirone has economic advantages in treating schizophrenia patients compared to other commonly used atypical antipsychotic drugs.

Objective:To investigate the predictive value of trigeminal nerve vascular compression grading evaluated by preoperative magnetic resonance imaging (MRI) in patients with trigeminal neuralgia (TN) after microvascular decompression (MVD).Methods:Two hundred and seventy patients with TN accepted MVD in our hospital from January 2015 to December 2017 were chosen in our study; their clinical and MRI data were retrospectively analyzed. By referring to Sindou's method and Jannetta standard, these patients were divided into patients with mild vascular compression ( n=71) and patients with severe vascular compression ( n=199) according to preoperative MRI data; these patients were divided into typical TN patients ( n=219) and atypical TN patients ( n=51) according to their symptomatic characteristics; the differences in prognoses after one year of follow-up were compared among patients from different categories. Results:The degree of intraoperative vascular compression was basically consistent with the preoperative imaging evaluation results, and the intraoperative vascular compression in 256 patients was consistent with preoperative imaging evaluation grading, with a coincidence rate of 94.8% (256/270). The difference in prognosis between patients with mild vascular compression and patients with severe vascular compression was statistically significant ( Z=-3.420, P=0.001), and the mean rank indicated that the prognosis of patients with severe vascular compression was better than that of patients with mild vascular compression (142.01 vs. 117.25). The prognosis difference between typical TN patients and atypical TN patients was statistically significant ( Z=-5.810, P=0.000), and the mean rank indicated that the prognosis of typical TN patients was better than that of atypical TN patients (144.45 vs. 97.08). Conclusions:Preoperative MR imaging evaluation is a reliable method to assess the degree of vascular compression. Patients with severe vascular compression and typical TN have high postoperative pain relief rate after MVD.

In modern medicine, bone and dental loss and defects are common and widespread morbidities, for which regenerative therapy has shown great promise. Mesenchymal stem cells, obtained from various sources and playing an essential role in organ development and postnatal repair, have exhibited enormous potential for regenerating bone and dental tissue. Currently, mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering. Nevertheless, the efficacy of MSC-based regeneration is not always fulfilled, especially in diseased microenvironments. Specifically, the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs, both as donors and recipients. Accordingly, approaches targeting a diseased microenvironment have been established, including improving the diseased niche to restore endogenous MSCs, enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies. Moreover, the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy. In this review, we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment, emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.