BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.

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

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Centrifugal blood pumps drive blood flow by regulating blood flow rate,and have been widely used in clinical applications,including extracorporeal membrane oxygenation(ECMO),cardiopulmonary bypass(CPB),and extracorporeal circulation carbon dioxide removal(ECCO2R).However,because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios,blood pumps face different application conditions in clinical use.In this study,the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Background:There is a link between dysbiosis or disorder of gut microbiota and brain and liver diseases,and gut microbiota may affect the occurrence and development of primary biliary cholangitis(PBC)and depression through the gut-liver-brain axis.Aims:To analyze the gut microbiota in PBC mice associated with depression by using 16S rRNA gene sequencing technology.Methods:Twelve female mice were randomly divided into control group,cholestasis group,cholestasis+depression group and treatment group.Mice in the control group were given normal feed and water.Mice in the cholestasis group were fed with a feed containing 0.1%DDC for 2 weeks to establish cholestasis model.Mice in the cholestasis+depression group were stimulated with chronic mild unpredictable stress for 2 weeks,followed by 2 weeks of 0.1%DDC-containing feed to establish cholestasis+depression model.Mice in the treatment group were injected intraperitoneally with clomipramine hydrochloride(7.5 mg·kg-1·d-1)for 2 weeks based on the construction of cholestasis+depression model.During the modeling period,the behavioral changes of the mice were observed.After the modeling,the body weight was recorded,and the weight-bearing swimming test,forced swimming test,tail suspension test and HE staining of liver tissue were performed.The fresh feces were collected,and the changes of gut microbiota were analyzed by 16S rRNA gene sequencing technology.Results:Compared with the control group,the body weight of mice in cholestasis group and cholestasis+depression group was significantly decreased(P<0.05),and the depression-like behavior was significantly aggravated(P<0.05);compared with the cholestasis+depression group,the body weight of mice in treatment group was significantly increased(P<0.05),and the depression-like behavior was significantly ameliorated(P<0.05).Various degrees of cholestatic injury of the liver tissue were observed in the cholestasis group,cholestasis+depression group and treatment group.Compared with the cholestasis+depression group,the pathological injury of the liver tissue in treatment group was significantly reduced.After sequencing and flattening,5 491 operational taxonomic units(OTUs)were obtained in fecal samples.There were 162 common OTUs among the 4 groups.The microbial diversity and community composition of the control group,cholestasis group,cholestasis+depression group and treatment group were significantly different.At the phylum level,the abundance of Firmicutes in the cholestasis group was significantly increased;the abundance of Proteobacteria in the cholestasis+depression group was significantly increased;the abundance of both Firmicutes and Proteobacteria was significantly increased in the treatment group,while the abundance of Bacteroidetes was significantly decreased.LEfSe analysis was performed in species with significant differences among the groups,and the results showed that there were 38 microbial groups with LDA value>4.Conclusions:Significant changes are observed in gut microbiota composition and diversity in mice with PBC associated with depression.Antidepressant treatment can improve the abundance and diversity of gut microbiota,and regulating gut microbiota may become a new treatment strategy for PBC associated with depression.

Objective:To systematically evaluate the qualitative research on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients′experience of participating in advance care planning (ACP), so as to provide reference for the application of ACP in HIV/AIDS patients.Methods:Computer searched qualitative studies on HIV/AIDS patients′participation in ACP experience in Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, Wanfang, VIP, China Biomedical Literature Database. The search time limit was from inception to December 1, 2023, and the research results were integrated using Meta integration method after quality evaluation.Results:A total of 10 articles were included, and 58 research results were extracted, forming 12 new categories, and 4 integrated results were obtained: HIV/AIDS patients′understanding of ACP; attitudes of HIV/AIDS patients towards ACP; the influencing factors of HIV/AIDS patients′participation in ACP; suggestions for implementing ACP for HIV/AIDS patients.Conclusions:Medical staff should promptly identify the needs of HIV/AIDS patients for ACP, help them increase their awareness and acceptance of ACP. At the same time, based on China′s unique cultural background and healthcare system, relevant laws and regulations should be continuously improved to promote the development and improvement of ACP in China.

Objective:To analyze the clinical characteristics of patients with inflammatory bowel disea-ses(IBD)in pre-pregnancy,pregancy and loctation.Methods:The clinical data of pregnancy compli-cated with IBD in Department of Obstetrics and Gynecology of Peking University Third Hospital and deli-very from September 2011 to June 2022 were collected.The clinical characteristics of the patients were analyzed retrospectively.According to the state of diseases during pre-pregnancy,pregnancy and lactation,the patients were divided into active and remission group,and the two groups were compared interms of pre-pregnancy counseling,nutritional status,pregnancy and delivery complications,gestational week,mode of delivery,and neonatal outcome.Results:A total of 33 pregnant women with IBD were included in this study,of which 7 delivered a second child,for a total of 40 deliveries,with 36 natural pregnan-cies(90.0％)and 4 assisted reproductions(10.0％).Among the 40 cases,21 cases(52.5％)were sustained in remission in pre-pregnancy,pregnancy and lactation,and 19 cases(47.5％)in disease ac-tivity,of which 8 cases(42.1％)were due to self-withdrawal of drugs or failure to take medicine regu-larly.Compared with the activity group,the disease remission group had a higher rate of pre-pregnancy counseling(57.1％vs.15.8％,P=0.010),and higher levels of hemoglobin[(112.67±8.53)g/L vs.(102.84±5.23)g/L,P＜0.001],serum total protein[(66.58±6.34)g/L vs.(60.83±6.25)g/L,P=0.006],serum albumin[36.4(35.1,38.3)g/L vs.34.3(31.1,35.6)g/L,P=0.006],se-rum calcium[(2.25±0.10)μmol/L vs.(2.13±0.15)μmol/L,P=0.004],but a lower incidence of gestational hypertensive disorders(0 vs.31.6％,P=0.007).In 40 deliveries,there were 27 cases of vaginal delivery(67.5％),13 cases of cesarean section(32.5％).The analysis of neonatal outcomes showed 38 full-term deliveries and 2 preterm deliveries;1 case of macrosomia,1 case of small-for-gesta-tional-age,1 case of low birth weight and 3 cases of birth defects.There were 10 newborns admitted to neonatal intensive care unit,including 4 cases of neonatal infections and 2 cases of neonatal jaundice.Conclusion:Pre-pregnancy counseling and evaluation of IBD patients are very important,and good preg-nancy outcomes can be obtained through careful management during pregnancy in the most of the pa-tients.