OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

The persistence of obesity is rooted in energy storage mechanisms formed through millions of years of evolution, combined with the systematic influence of the modern "obesogenic environment", constituting a complex regulatory network involving coordinated neural, endocrine, and metabolic systems. Current mainstream treatment methods exhibit significant limitations: glucagon-like peptide-1 receptor agonists demonstrate remarkable short-term weight loss effects but present issues with tolerance development and post-discontinuation weight regain; bariatric metabolic surgery similarly faces long-term weight recurrence challenges, with approximately one-third of patients experiencing weight regain within five years after surgery. Therefore, comprehen-sive obesity treatment must establish a new paradigmatic framework: utilizing cognitive behavioral intervention as the therapeutic foundation, employing multi-dimensional strategies including mindful eating training, nutritional management, and exercise intervention to help patients establish sustain-able lifestyle changes; repositioning pharmaceutical and surgical medical interventions as supportive measures for behavioral change; constructing multi-level social support environments encompassing policy, community, and family domains to achieve transformation from treatment goals focused solely on weight reduction to metabolic health improvement, from success definition based on short-term weight loss to long-term maintenance, and from medical-dominated treatment systems to patient-centered multidisciplinary collaborative approaches. Ultimately, through the deep integration of biomedical precision, patient cognitive initiative, and social support inclusiveness, a sustainable collaborative pathway for obesity treatment can be established. Based on twenty years of clinical experience in bariatric and metabolic surgery, the authors provide an in-depth analysis of the treat-ment challenges faced by obesity as a complex disease and proposes the necessity of transitioning from traditional single medical interventions to a biopsychosocial comprehensive treatment model.

Objective:To explore the clinical effects of various special forms of the descending branch of the lateral circumflex femoral artery (DLCFA) perforator flaps in repairing high-voltage electrical burn wounds on the wrist.Methods:This study was a retrospective observational study. From September 2014 to June 2024, 79 male patients with high-voltage electrical burns on the wrist, aged 20 to 62 years and met the inclusion criteria, were admitted to Beijing Jishuitan Hospital Affiliated to Capital Medical University, with wrist high-voltage electrical burn wound (hereinafter referred to as wrist wound) types being classified as type Ⅱ or type Ⅲ. In the early stage after injury, debridement was performed on the patients' wrists. Based on the wound condition and flap indications, the flow-through, lobed, chimeric, flow-through-lobed, lobed-chimeric, flow-through-chimeric, or flow-through-lobed-chimeric DLCFA perforator flap was employed individually, and the flow-through-chimeric DLCFA perforator flap and tensor fascia lata myocutaneous flap were employed in combination to repair the wounds. The donor site wounds were repaired using direct sutures or skin grafting. The number of various DLCFA perforator flaps resected during surgery and the number of various types of wrist wounds repaired were recorded, as well as the closure status of the donor site wound. The postoperative flap survival, occurrence of vascular crisis, wound or suture site healing, and patency of the reconstructed artery in flow-through flaps were recorded. During follow-up, the appearance of the flap, scar formation, and the presence of thigh muscle herniation were observed.Results:Intraoperatively, 11 flow-through DLCFA perforator flaps were resected to repair 11 type Ⅱ wrist wounds, 13 lobed DLCFA perforator flaps were resected to repair 9 type Ⅱ and 4 type Ⅲ wrist wounds, 16 chimeric DLCFA perforator flaps were resected to repair 16 type Ⅱ wrist wounds, 11 flow-through-lobed DLCFA perforator flaps were resected to repair 5 type Ⅱ and 6 type Ⅲ wrist wounds, 10 lobed-chimeric DLCFA perforator flaps were resected to repair 5 type Ⅱ and 5 type Ⅲ wrist wounds, 6 flow-through-chimeric DLCFA perforator flaps were resected to repair 6 type Ⅱ wrist wounds, 7 flow-through-lobed-chimeric DLCFA perforator flaps were resected to repair 7 type Ⅲ wrist wounds, and 5 flow-through-chimeric DLCFA perforator flaps combined with tensor fascia lata myocutaneous flaps were resected to repair 5 type Ⅲ wrist wounds. Seventy-four patients had their donor site wounds closed by direct suturing, while 5 patients had their donor site wounds closed by skin grafting. Postoperatively, the flaps in 3 patients developed vascular crisis, including 1 case of arterial crisis and 2 cases of venous crises but survived after emergency vascular exploration and other treatments; the remaining flaps survived completely. Postoperatively, 3 patients had seepage beneath their flaps, which were closed after dressing changes; the remaining patients' wounds or suture sites all healed. Anteriography showed that all reconstructed arteries in 35 patients who underwent flow-through flap transplantation were patent postoperatively. During the follow-up period of 3 months to 1 year, 20 patients had bloated flap, while the rest had good flap appearance; linear scars were left in the donor sites that underwent direct wound closure, and the skin-grafted areas of the donor site wounds showed no significant patchy hypertrophic scarring; no thigh muscle herniation occurred.Conclusions:Taking the full advantage of perforator flaps, various special forms of the DLCFA perforator flaps are used to repair the three-dimensionally injury wounds caused by high-voltage electrical burns on the wrist, which not only minimizes the damage to the donor site but also allow the recipient site to be well repaired, showing good appearance in the recent follow-up.

Objective To investigate the brain voxel-mirrored homotopic connectivity(VMHC)alterations in patients with ves-tibular migraine(VM)by using resting-state functional magnetic resonance imaging(rs-fMRI).Methods The rs-fMRI data of 30 VM patients(VM group)and 30 healthy volunteers(control group)were prospectively collected.The brain VMHC values in all subjects were calculated and the differences between the two groups were compared.The correlations between VMHC values of significant brain regions and clinical scale scores were analyzed in the VM group.Results Compared with the control group,the VMHC values of the cerebellum region 6,orbital inferior frontal gyrus,insula,superior temporal gyrus and postcentral gyrus in the VM group were all decreased[cluster-level family wise error(FWE)corrected,Pvoxel-level<0.001,Pcluster-level<0.05].In the VM group,the VMHC values of the postcentral gyrus were negatively correlated with dizziness handicap inventory(DHI)score(r=-0.383,P=0.037).Additionally,the VMHC values of the insula were negatively correlated with headache impact test-6(HIT-6)score(r=-0.430,P=0.018).Conclusion VM patients have altered VMHC in certain brain regions,indicating related dysfunctions in vestibule,pain,hearing and emotion.

Objective:This study was to explore the behavioral and electroencephalographic characteristics of impaired cognitive flexibility in patients with obsessive-compulsive disorder (OCD) with comorbid obsessive-compulsive personality disorder(OCPD).Methods:A cross-sectional study was designed to collect data prospectively from OCD patients who visited the psychology departments at two top-tier hospitals in Changsha between September 2019 and December 2021. The study included 31 patients with OCD+OCPD(18 males, 13 females; aged 15-46 (22.8±8.4) years) and 39 patients with OCD only(25 males, 14 females; aged 15-34 (21.6±4.2) years). Additionally, 32 age-matched healthy controls(HC: 18 males, 14 females; aged 18-25 (20.8±1.7) years). All participants completed the Task-Switching paradigm while behaioral and event-related potentials(ERPs) were recorded simultaneously. Repeated measures analysis of variance was used to compare the group differences in behavioral and ERP data(electrode sites: FZ, FCZ, CZ, PZ; ERP components: amplitude and latency of P2, N2, and P3).Results:The reaction times in both the comorbid and OCD groups were significantly longer than those in the healthy control group ((1 182±287) ms and (1 119±194) ms vs. (886±95) ms; F=18.48, both P<0.001). Accuracy rates in the comorbid and OCD groups were also significantly lower than in the healthy control group ((77±14)% and (77±13)% vs. (84±7)%; F=4.00, both P<0.05). In the task-switching condition, the N2 latency at the CZ electrode was significantly shorter in the comorbid and OCD groups compared to the healthy control group ((290±22) ms and (291±29) ms vs. (308±27) ms; F=3.81, both P<0.05). Furthermore, at the FZ and FCZ electrodes, the N2 latency in the comorbid group was significantly shorter in the switching task compared to the repetition task. Conclusion:OCD patients with comorbid OCPD show more severe cognitive flexibility impairments and display abnormal electrophysiological patterns.

Objective To evaluate the dosimetric impact of interfractional bladder fullness variation in volumetric modulated arc therapy for cervical cancer using artificial intelligence-assisted cone-beam CT(CBCT)image segmentation,and propose an imaging-based quantitative assessment criterion for bladder fullness,providing an objective basis for assessing bladder filling status during clinical treatment.Methods Fifty patients receiving volumetric modulated arc therapy for cervical cancer were selected.The criterion for determining bladder fullness was as follow:if the bladder longitudinal diameter measured on the CBCT mid-sagittal plane was greater than half of the bladder longitudinal diameter measured on the localizable CT,it was defined as≥50%bladder fullness;otherwise,it was defined as<50%bladder fullness.Based on this criterion,two CBCT images were selected for each patient(representing fractions with≥50%and<50%fullness,respectively).Borui auto-contouring system was applied to re-contour the target areas and organs at risk,followed by dose recalculation.Results Compared with≥50%bladder fullness group,<50%bladder fullness group had significantly increased bladder V40,and small bowel Dmax,Dmean,V55,V45,V40(P<0.05),indicating that during interfractional radiotherapy,a CBCT-measured bladder longitudinal diameter less than half of the bladder longitudinal diameter measured on the localizable CT could serve as a predictor for significantly increased radiation dose to the bladder and small bowel.Correlation analysis revealed that bladder volume change showed a positive correlation with bladder Dmax change(R=0.45),a significant negative correlation with bladder V30(R=-0.37),and negative correlations with small bowel Dmax,Dmean,V55,V45,V40(R=-0.31,-0.41,-0.39,-0.49,-0.61).The correlation results indicate that increasing bladder fullness could reduce the radiation dose to the bladder and small bowel.Conclusion Artificial intelligence-assisted segmentation confirms that in interfractional radiotherapy for cervical cancer,when the CBCT-measured bladder longitudinal diameter is less than half of the longitudinal diameter measured on the localizable CT,there is a significant increase in radiation dose to OAR.Maintaining an ideal state of bladder fullness contributes to reducing the radiation dose to the bladder and small bowel.It is crucial to provide patients with adequate bladder management education before treatment and implement strict bladder volume management strategies during treatment fractions.

In recent years, the rapid development of transportation and sports industries, coupled with the accelerated population aging in China, has led to a steady increase in the incidence of articular cartilage injuries, wear, and degenerative changes. Currently, the clinical treatment options for cartilage defects primarily include conservative therapies and surgical interventions, both of which have certain limitations. Cartilage tissue engineering (CTE), as a novel technology, provides an infinite prospect for cartilage regeneration and repair. Because of the abilities of scaffolds to mimic the natural cartilage structure, exhibit excellent biocompatibility and biomimetic mechanical properties, and promote cell adhesion and proliferation, scaffolds are considered effective delivery systems for growth factors, genes, and drugs. This review summarizes the clinical treatments for cartilage defects and their limitations, discusses the materials and preparation techniques of scaffolds used in CTE, with a particular focus on drug-loaded scaffold delivery systems in cartilage repair and regeneration, and offers a perspective on the future application of drug-loaded CTE. The aim is to provide theoretical guidance and new approaches for the repair of cartilage defects.
Tissue Engineering/methods* ; Humans ; Tissue Scaffolds ; Drug Delivery Systems/methods* ; Regeneration ; Cartilage, Articular/physiology* ; Animals ; Biocompatible Materials

Drug clinical trial is a method of experimental epidemiology to evaluate the effectiveness and safety of medicines.This article introduced the types and design thought of innovation in drug clinical trial design,and provided methodological reference for related researches.Adaptive design is a complex and innovative clinical trial design,which can be divided into group sequential design,sample size re-estimation,seamless trial,enrichment design and master protocol design(basket trial,umbrella trial,platform trial,etc.)according to the purpose of adaptability.The adaptive design has greater adjustment flexibility,which overcomes the shortcomings of conventional clinical trials to a certain extent,then improves the validity of the trial results and the strength of the evidence.The design innovation and remodeling of drug clinical trials will provide more powerful evidence-based evidence for the realization of precision medicine.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective:To investigate the mechanism by which microRNA-183 (miR-183) regulates the progression of diabetic nephropathy (DN) through targeting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and modulating the AKT signaling pathway, and to identify potential therapeutic targets for DN.Methods:(1) Bioinformatic analysis of miRNA expression: MiRNA expression datasets from diabetic nephropathy (DN) and control samples were obtained from the Gene Expression Omnibus database. Differential expression analysis was performed, and differentially expressed miRNAs (DEmiRNAs) were identified using thresholds of an absolute log 2 (fold changes) >1 and an adjusted P-value<0.05. The results were visualized in a volcano plot and a heatmap. (2) Animal model establishment and in vivo interventional studies: A DN rat model was induced by administration of a high-fat/high-sucrose diet combined with an intraperitoneal injection of streptozotocin. Rats were randomly assigned into four groups ( n=10 per group) using a random number table: control group, DN model group, miR-183 inhibitor negative control (NC) group, and miR-183 inhibitor group. The latter two groups received tail vein injections of the miR-183 inhibitor NC or the miR-183 inhibitor, respectively, for eight consecutive weeks. Parameters including fasting blood glucose, 24-hour urinary protein excretion, urinary albumin excretion rate (UAER), serum creatinine, and blood urea nitrogen (BUN) were measured. Renal histopathological changes were assessed by HE and PAS staining. Furthermore, the expression of candidate miRNAs from patient data was validated, and the mechanism of action of miR-183 was investigated using quantitative real-time PCR and Western blotting. (3) In vitro mechanistic investigations in cultured podocytes: Mouse podocyte clone-5 (MPC5) cells were cultured in vitro and subjected to the following conditions: normal glucose (5.3 mmol/L glucose), high glucose (30 mmol/L glucose), and osmotic control (5.3 mmol/L glucose+19.5 mmol/L mannitol). Cells in the logarithmic growth phase were transfected with the miR-183 inhibitor (100 nmol/L), miR-183 mimic (50 nmol/L), or their corresponding negative controls. A dual-luciferase reporter assay was conducted to validate the binding interaction between miR-183 and the 3'-untranslated region (3'UTR) of PTEN. The effects of miR-183 on the AKT signaling pathway, apoptosis-related proteins, and cell viability were evaluated by quantitative real-time PCR, Western blotting, and the cell counting kit-8 assay, respectively. Results:MiR-183 expression was markedly upregulated in renal tissues from DN patients and DN model rats (both P<0.05). Inhibition of miR-183 significantly reduced renal miR-183 levels by 90.2% ( P<0.01), decreased fasting blood glucose by 65.3% ( P<0.01), and improved renal function parameters, including reductions in urinary protein (40.3%), blood urea nitrogen (32.1%), urinary albumin excretion rate (22.5%), and serum creatinine (40.2%) (all P<0.01). Histological analyses showed attenuation of glomerular lesions and glycogen accumulation. Bioinformatic prediction and experimental validation identified PTEN as a direct target of miR-183, confirmed by dual-luciferase assays. In vitro, miR-183 inhibition increased PTEN expression, reduced AKT phosphorylation, promoted podocyte proliferation, and suppressed apoptosis (upregulation of Bcl-2 and downregulation of cleaved-caspase-3). These effects were abolished upon PTEN knockdown. Conclusions:miR-183 aggravates DN by targeting PTEN and activating the AKT signaling pathway. Inhibition of miR-183 improves renal function and reduces podocyte apoptosis, suggesting miR-183 as a potential therapeutic target for DN.