BACKGROUND:The absence of blood vessels in tendon tissue makes tendon repair challenging.Therefore,improving tendon healing and raising the efficacy of stem cell and other therapeutic cell transplantation after tendon damage have become hotspots for research in both clinical and scientific contexts. OBJECTIVE:The stem cells and gelatin microcarrier scaffold were joined to form tissue engineered stem cells.Human umbilical cord mesenchymal stem cells cultured in gelatin microcarriers were used to investigate the therapeutic impact and mode of action on tendinopathy healing in rats in vitro and In vivo. METHODS:(1)In vitro cell experiments:After seeding human umbilical cord mesenchymal stem cells with three-dimensional gelatin microcarriers,the cell vitality and survival were assessed.Human umbilical cord mesenchymal stem cells conventionally cultured were cultured as controls.(2)In vivo experiment:Adult SD rats were randomly assigned to normal group,tendinopathy group,2D group(tendinopathy+conventional culture of human umbilical cord mesenchymal stem cells),and 3D group(tendinopathy+gelatin microcarrier three-dimensional culture of human umbilical cord mesenchymal stem cells),with 6 rats in each group.Four weeks after therapy,animal behavior tests and histopathologic morphology of the Achilles tendon was examined. RESULTS AND CONCLUSION:(1)In vitro cell experiments:the seeded human umbilical cord mesenchymal stem cells on gelatin microcarriers showed high viability and as time went on,the stem cell proliferation level grew.Compared with the control group,3D stem cell culture preserved cell viability.(2)In vivo experiment:Following a 4-week treatment,the 3D stem cell culture group showed a significant improvement in both functional recovery of the lower limbs and histopathological scores when compared to the tendinopathy group.The 2D stem cell culture group also showed improvement in tendinopathy injury,but its effect is not as much as the 3D stem cell culture group.(3)The outcomes demonstrate that human umbilical cord mesenchymal stem cells cultured with three-dimensional gelatin microcarrier can promote the repair and regeneration of tendon injury tissue,and the repair effect is better than that of conventional human umbilical cord mesenchymal stem cells.

Objective To investigate the predictive value of combining polygenic risk score(PRS)with the National Institutes of Health Stroke Scale(NIHSS)socre for the development of deep venous thrombosis(DVT)in patients with ischemic stroke.Methods A total of 150 patients with ischemic stroke who were hos-pitalized in Jilin Provincial People's Hospital from December 2023 to May 2024 were selected as study sub-jects.After excluding patients who did not meet the criteria,139 patients were successfully followed up and di-vided into two groups based on whether DVT occurred.PRS strategy and fluorescence in situ hybridization(FISH)technology were used to detect the mutation of the gene loci associated with the risk of venous throm-boembolism(VTE).Based on these genotype data and the effect size of single nucleotide polymorphism(SNP)loci,the PRS score of patients was calculated through the model formula.The degree of neurological impairment was evaluated by NIHSS score.Receiver operating characteristics(ROC)curve was used to ana-lyze the efficacy of PRS score,NIHSS score and their combination in predicting ischemic stroke with lower limb DVT,and clinical data related to VTE formation were collected.Results There were no statistically sig-nificant differences between the two groups in terms of gender,age,body mass index(BMI),smoking,alcohol consumption,hypertension,diabetes,D-dimer(D-D),total cholesterol(TC),triglycerides(TG),and lipopro-tein(a)[(LP(a)]levels(P＞0.05).The PRS score,NIHSS score,and Barthel index in the DVT group were significantly higher than those in the non-DVT group,and the proportion of patients with bed rest exceeding 72 h and homocysteine(Hcy)levels were also relatively higher,with statistical significance(P＜0.05).Logis-tic regression analysis showed that PRS score＞2.55,NIHSS score ≥-3 and Barthel index＜60 were inde-pendent risk factors for lower limb DVT after ischemic stroke(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of PRS score,NIHSS score and combined prediction of ischemic stroke combined with lower limb DVT were 0.655,0.747 and 0.763,respectively,and the AUC of combined predic-tion was higher than that of single prediction(P＜0.05).Conclusion PRS score combined with NIHSS score has good predictive efficacy for ischemic stroke complicated with DVT.

Objective:To overview the systematic reviews/meta-analyses of TCM treatment for gastroesophageal reflux disease (GERD); To provide evidence-based support for clinical decision-making in the treatment of GERD with Chinese materia medica.Methods:Systematic reviews/meta-analyses of RCTs about the treatment of GERD with Chinese materia medica were retrieved from databases of CNKI, Wanfang Data, Chongqing VIP, CBM, EMbase, PubMed and Cochrane Library from January 1, 2018 to December 31, 2023. AMSTAR 2 scale, PRISMA 2020 and GRADE system were used to evaluate the methodological quality, reporting quality and evidence quality of the included studies.Results:A total of 19 systematic reviews/meta-analyses were included. The AMSTAR 2 evaluation showed that 17 of the included studies were rated as low-quality, and 2 were rated as extremely low-quality. The PRISMA 2020 evaluation results showed that the included literature scored 14.5-21 points, with 18 articles having certain reporting defects and 1 article having serious reporting defects. The GRADE evaluation results showed 1 high-quality index, 31 medium-quality indexes, 34 low-quality indexes, and 10 extremely low-quality indexes.Conclusion:TCM has a certain therapeutic effect on GERD, but the overall methodological quality, reporting quality, and evidence quality still need to be further improved.

OBJECTIVE: To review the research progress of pathological changes of glenohumeral capsule in patients with recurrent shoulder anterior dislocation (RSAD). METHODS: The literature on shoulder capsules, both domestic and international, was reviewed. The anatomy, histology, and molecular biology characteristics of the glenohumeral capsule in RSAD patients were summarized. RESULTS: Anatomically, the glenohumeral capsule is composed of four distinct parts: the upper, lower, anterior, and posterior sections. The thickness of these sections is uneven, and the stability of the capsule is further enhanced by the presence of the glenohumeral and coracohumeral ligaments. Histologically, the capsule tissue undergoes adaptive changes following RSAD, which improve its ability to withstand stretching and deformation. In the realm of molecular biology, genes associated with the regulation of structure formation, function, and extracellular matrix homeostasis of the shoulder capsule's collagen fibers exhibit varying degrees of expression changes. Specifically, the up-regulation of transforming growth factor β ₁ (TGF-β ₁), TGF-β receptor 1, lysyl oxidase, and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 facilitates the repair of the joint capsule, thereby contributing to the maintenance of shoulder joint stability. Conversely, the up-regulation of collagen type Ⅰ alpha 1 (COL1A1), COL3A1, and COL5A1 is linked to the recurrence of shoulder anterior dislocation, as these changes reflect the joint capsule's response to dislocation. Additionally, the expressions of tenascin C and fibronectin 1 may play a role in the pathological processes occurring during the early stages of RSAD. CONCLUSION Glenohumeral capsular laxity is both a consequence of RSAD and a significant factor contributing to its recurrence. While numerous studies have documented alterations in the shoulder capsule following RSAD, further research is necessary to confirm the specific pathological anatomy, histological, and molecular biological changes involved.
Humans ; Joint Capsule/metabolism* ; Shoulder Dislocation/metabolism* ; Recurrence ; Shoulder Joint/metabolism* ; Tenascin/metabolism* ; Transforming Growth Factor beta1/genetics* ; Collagen Type I/genetics* ; Extracellular Matrix/metabolism*

OBJECTIVE: To compare the effectiveness and advantages of the double reverse traction reduction versus open reduction internal fixation for treating complex tibial plateau fractures. METHODS: A clinical data of 25 patients with Schatzker type Ⅴ or Ⅵ tibial plateau fractures, who met the selection criteria and were admitted between January 2019 and January 2023, was retrospectively analyzed. Thirteen patients underwent double reverse traction reduction and internal fixation (double reverse traction group), while 12 patients underwent open reduction and internal fixation (traditional open group). There was no significant difference in the baseline data (age, gender, injury mechanism, Schatzker classification, interval between injury and operation) between the two groups ( P>0.05). The effectiveness were evaluated and compared between the two groups, included operation time, intraoperative blood loss, incision length, hospital stay, full weight-bearing time, complications, fracture healing, Rasmussen radiological score (reduction quality), knee Hospital for Special Surgery (HSS) score, and knee flexion/extension range of motion. RESULTS: The double reverse traction group demonstrated significantly superior outcomes in operation time, intraoperative blood loss, hospital stay, incision length, and time to full weight-bearing ( P<0.05). Two patients in traditional open group developed incisional complications, while the double reverse traction group had no complication. There was no significant difference in the incidence of complication between the two groups ( P>0.05). All patients were followed up 24-36 months (mean, 30 months), with no significant difference in follow-up duration between groups ( P>0.05). Fractures healed in both groups with no significant difference in healing time ( P>0.05). At 6 months after operation, Rasmussen radiological scores and grading showed no significant difference between the two groups ( P>0.05); the double reverse traction group had significantly higher HSS scores compared to the traditional open group ( P<0.05). At 12 months after operation, knee flexion/extension range of motion were significantly greater in the double reverse traction group than in the traditional open group ( P<0.05). CONCLUSION Double reverse traction reduction offers advantages over traditional open reduction, including shorter operation time, reduced blood loss, minimized soft tissue trauma, and improved joint functional recovery. It is a safe and reliable method for complex tibial plateau fractures.
Humans ; Tibial Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Male ; Female ; Traction/methods* ; Retrospective Studies ; Middle Aged ; Adult ; Open Fracture Reduction/methods* ; Treatment Outcome ; Range of Motion, Articular ; Fracture Healing ; Operative Time ; Length of Stay ; Blood Loss, Surgical ; Aged ; Tibial Plateau Fractures

Objective: To explore the causal relationship between gut microbiota and upper urinary tract stones using Mendelian randomization (MR) analysis，and to investigate the potential mediating role of plasma metabolites. Methods: Data on gut microbiota，plasma metabolites，and upper urinary tract stones were obtained from publicly available Genome-wide Association Studies (GWAS).Bidirectional MR analysis was performed to examine the causal relationship between gut microbiota and upper urinary tract stones.Subsequently，a two-step MR approach was employed to determine whether gut microbiota contribute to upper urinary tract stones through plasma metabolites，and the mediating effects and mediator ratio were calculated.The inverse variance weighted (IVW) method was used as the primary analytical tool，supplemented by Bayesian weighted Mendelian randomization (BWMR)，MR-Egger，and weighted median (WM) analyses.Horizontal pleiotropy and heterogeneity tests were conducted to ensure the robustness of the findings. Results: Bidirectional MR analysis identified causal associations between 7 gut microbial taxa and 6 microbial metabolic pathways with upper urinary tract stones，while the development of upper urinary tract stones affected 13 gut microbial taxa and 5 metabolic pathways.Additionally，43 plasma metabolites (including 27 identified metabolites，8 unidentified metabolites，and 8 metabolite ratios) were causally associated with upper urinary tract stones.The two-step MR analysis identified 11 potential causal pathways.After metabolic pathways and unidentified metabolites were excluded，a causal link mediated by Bacteroides faecis between galactarate and upper urinary tract stones was confirmed，with a mediation proportion of 16.99% (95%CI：5.76%-33.95%，P=0.0371). Conclusion: This study establishes a causal relationship between parabacteroides and upper urinary tract stones，and elucidates the mediating role of galactarate，offering new insights into the pathogenesis and prevention strategies for upper urinary tract stones.

OBJECTIVES: To synthesize a temperature-responsive multimodal motion microrobot (MMMR) using temperature and magnetic field-assisted microfluidic droplet technology to achieve targeted drug delivery and controlled drug release. METHODS: Microfluidic droplet technology was utilized to synthesize the MMMR by mixing gelatin with magnetic microparticles. The microrobot possessed a magnetic anisotropy structure to allow its navigation and targeted drug release by controlling the temperature field and magnetic field. In the experiment, the MMMR was controlled to move in a wide range along a preset path by rotating a uniform magnetic field, and the local circular motion was driven by a planar rotating gradient magnetic field of different frequencies. The MMMR was loaded with simulated drugs, which were released in response to laser heating. RESULTS: Driven by a rotating magnetic field, the MMMR achieved linear motion following a predefined path. The planar gradient rotating magnetic field controlled circular motion of the MMMR with an adjustable radius, utilizing the centrifugal force generated by rotation. The drug-loaded MMMR successfully reached the target location under magnetic guidance, where the gelatin matrix was melted using laser heating for accurate drug release, after which the remaining magnetic particles were removed using magnetic field. CONCLUSIONS The MMMR possesses multimodal motion capabilities to enable precise navigation along a predefined path and dynamic regulation of drug release within the target area, thus having great potential for a wide range of biomedical applications.
Drug Delivery Systems/methods* ; Temperature ; Drug Liberation ; Magnetic Fields ; Robotics ; Gelatin/chemistry* ; Delayed-Action Preparations ; Microfluidics ; Motion

OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Objective To explore the application value of the nomogram based on dual-energy CT in preoperative evaluation of human epidermal growth factor receptor 2(HER-2)status in patient with breast cancer.Methods A total of 269 patients with pathologically confirmed breast cancer were retrospectively collected and randomly divided into a training cohort(n=189)and a validation cohort(n=80)at a ratio of 7︰3.The dual-energy CT parameters and clinical features of all patients were measured and collected.Varia-bles with significant difference in univariate analysis were included in the multivariate logistic analysis to obtain independent risk fac-tors related to HER-2 status,with establishing a nomogram model.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive performance of the nomogram.Results There was a significant difference in axillary lymph node enlargement between the two groups(P<0.05).The venous phase iodine concentration(IC)and normalized iodine concentration(NIC)in the HER-2 positive group were significantly higher than those in the HER-2 negative group(P<0.05).Axillary lymph node enlargement,venous phase IC,and venous phase NIC were the independent risk factors for predicting HER-2 status in breast cancer.The nomogram con-structed from the above features exhibited good predictive performance,with area under the curve(AUC)of 0.856 and 0.834 in the training and validation cohorts,respectively.Conclusion The nomogram based on dual-energy CT has a high predictive value for HER-2 status in breast cancer patients.

Objective To explore the application value of a special fence in percutaneous transhepatic cholangial drainage(PTCD)under the guidance of C-arm CT.Methods A total of 43 patients who underwent PTCD were randomly divided into observation group and control group.The intervention operation in the observation group was guided by C-arm CT and located by special fence;in the control group,the intervention operation was only performed under digital subtraction angiography(DSA)fluoroscopy.Respectively,the differences in operation time,number of puncture needles and number of complications between the two groups were compared.Results The operation time,puncture times and complications in the observation group were(39.33±12.96)min,(1.67±0.80)times and 3 cases respectively;in the control group were(86.77±22.70)min,(3.41±1.26)times and 13 cases respectively;There were significant differences between the two groups(P<0.05).Conclusion The application of special fence in PTCD under the guidance of C-arm CT can short the operation time,reduce the number of punctures and reduce complications,which has important clinical application value.