Objective: To evaluate the clinical efficacy and safety of micro-percutaneous nephrolithotomy (microPCNL) using Needle-perc in the oblique supine-lithotomy position for treating 1—2 cm lower-pole stones (LPSs)，by comparing it with flexible ureteroscopic lithotripsy (FURL)，so as to identify an effective surgical method for LPSs. Methods: We retrospectively analyzed the clinical data of 56 patients with isolated LPSs of 1—2 cm treated in our hospital during Jan.and Dec.2023.Patients were divided into two groups based on the treatment method：FURL (n=31) and microPCNL (n=25).General information and perioperative data were compared between the two groups. Results: All operations were successfully completed.The operation time was shorter in the microPCNL group than in the FURL group \[(46.5±10.1) min vs.(73.5±18.9) min，P<0.001\].Stone-free rate (SFR) was 92.0% in the microPCNL group and 71.0% in the FURL group (P=0.026).There were no significant differences in the average fall of hemoglobin level，serumc creatinine change level，hospitalization time and postoperative fever between the two groups. Conclusion: MicroPCNL in oblique supine-lithotomy position is a safe and effective treatment for 1-2 cm LPSs，with a higher SFR compared to FURL.

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Objective:To investigate the clinicopathological factors and clinical significance of (micro)metastasis in No.12b lymph node in patients with gastric antrum cancer.Methods:This was a retrospective cohort study of data of 242 patients with gastric adenocarcinoma without distant metastasis, complete follow-up data, and no preoperative anti-tumor therapy or history of other malignancies. All study patients had undergone radical gastrectomy (at least D2 radical range) + No.12b lymph node dissection in the Department of Gastric Surgery of Liaoning Cancer Hospital from January 2007 to December 2012. Immunohistochemical staining with antibody CK8/18 was used to detect micrometastasis to lymph nodes. Patients with positive findings on hematoxylin and eosin stained specimens and/or CK8/18 positivity in No.12b lymph node were diagnosed as having No.12b (micro)metastasis and included in the No.12b positive group. All other patients were classified as 12b negative. We investigated the impact of No.12b (micro)metastasis by comparing the clinicopathological characteristics and recurrence free survival (RFS) of these two groups of patients and subjecting possible risk factors to statistical analysis.Results:Traditional hematoxylin-eosin staining showed that 15/242 patients were positive for No.12b lymph nodes and 227 were negative. A total of 241 negative No. 12b lymph nodes were detected. Immunohistochemical testing revealed that seven of these 241 No.12b lymph nodes (2.9%) were positive for micrometastasis. A further seven positive nodes were identified among the 227 nodes (3.1%) that had been evaluated as negative on hematoxylin–eosin-stained sections. Thus, 22 /242 patients' (9.1%) No.12b nodes were positive for micrometastases, the remaining 220 (90.9%) being negative. Factor analysis showed that No.12b lymph node (micro) metastasis is associated with more severe invasion of the gastric serosa (HR=3.873, 95%CI: 1.676-21.643, P=0.006), T3 stage (HR=1.615, 95%CI: 1.113-1.867, P=0.045), higher N stage (HR=1.768, 95%CI: 1.187-5.654, P=0.019), phase III of TNM stage (HR=2.129, 95%CI: 1.102-3.475, P=0.046), and lymph node metastasis in the No.1/No.8a/No.12a groups (HR=0.451, 95%CI: 0.121-0.552, P=0.035; HR=0.645, 95%CI:0.071-0.886, P=0.032; HR=1.512, 95%CI: 1.381-2.100, P=0.029, respectively). Survival analysis showed that the 5-year RFS of patients in the No.12b positive group was worse than that of those in the No.12b negative group (18.2% vs. 34.5%, P<0.001). Independent predictors of RFS were poorer differentiation of the primary tumor (HR=0.528, 95%CI:0.288-0.969, P=0.039), more severe serous invasion (HR=1.262, 95%CI:1.039-1.534, P=0.019), higher T/N/TNM stage (HR=4.880, 95%CI: 1.909-12.476, P<0.001; HR=2.332, 95%CI: 1.640-3.317, P<0.001; HR=0.139, 95%CI: 0.027-0.713, P=0.018, respectively), and lymph node metastasis in the No.12a/No.12b group(HR=0.698, 95%CI:0.518-0.941, P=0.018; HR=0.341, 95%CI:0.154-0.758, P=0.008, respectively). Conclusion:Detection of micrometastasis can improve the rate of positive lymph nodes. In patients with gastric antrum cancer, dissection of group No.12b lymph nodes may improve the prognosis of those with intraoperative evidence of tumor invasion into the serosa, more than two lymph node metastases, and suspicious lymph nodes in groups No.1 / No.8a / 12a.

Objective:To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds.Methods:Clinical data of 38 patients with large limb surface wound(11 cm×39 cm-16 cm×65 cm)admitted to the Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed.Eighteen patients were treated by anterolateral thigh perforator flap combined with superficial circumflex iliac artery flap(ALTP-SCIAP)with turbocharge technique(interregional flap group);while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps,combined with skin grafting if necessary(traditional anterolateral femoral flap group).The survival of skin flap,repair of donor area,complications and patient satisfaction were compared between the two groups.Results:In interregional flap group,18 flaps were harvested and transplanted,the flap width,length and the viable area were(9.9±2.0)cm,(44.2±3.5)cm and(343.2±79.9)cm2,respectively.In traditional anterolateral femoral flap group,29 flaps were harvested and transplanted,the flap width,length and the viable area were(11.0±2.8)cm,(21.7±3.2)cm and(186.4±49.2)cm2,respectively.There were significant differences in the flap length and the viable area between the two groups(t=22.365 and 8.345,both P<0.05).In the interregional flap group,the donor site of flap was closed by direct suture in 11 flaps,by skin retractor assisted suture in 6 flaps,and by skin grafting in one flap.In traditional anterolateral femoral flap group,the donor site of flap was closed by direct suture in 12 flaps,by skin retractor assisted suture in 11 flaps,and by skin grafting in 6 flaps.The skin graft rates of the two groups were 5.6%(1/18)and 20.7%(6/29),respectively(χ2=2.007,P>0.05).The interregional flap group had lower postoperative complications rate(5.6%vs.35.0%,χ2=4.942,P<0.05)and higher patient satisfaction rate(94.4%vs.70.0%,χ2=4.448,P<0.05)than traditional anterolateral femoral flap group.Conclusion:Compared with the traditional anterolateral femoral flap,the anterolateral femoral interregional flap with turbocharge technique has a larger flap area,most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.

Objective:To explore Lijin Zhenggu Therapy combined with heat supplementing needles on cartilage damage, immune balance, and liver X receptor NF-κB in knee osteoarthritis of New Zealand white rabbits.Methods:Totally　60 New Zealand white rabbits were divided into normal group, model group, Lijin Zhenggu Therapy group, heat supplementing needles group, and a combination group using random number table method, with 12 rabbits in each group. Except for the normal group, all other groups were established with knee osteoarthritis models. The Lijin Zhenggu Therapy group was treated with Lijin Zhenggu Therapy, the heat supplementing needles group was treated with heat supplementing needles, the combination group was treated with Lijin Zhenggu Therapy combined with heat supplementing needles. The pain threshold of each group of white rabbits was observed using a pain meter; HE staining was used to observe the morphology of cartilage damage in each group of white rabbits; ELISA was used to detect PGE 2, IL-1β and β-EP in the articular cartilage tissue of white rabbits in each group; PCR was used to detect the levels of LXRα and NF-κB mRNA. Western blot was used to detect toll like receptor 4 (TLR4), myeloid differentiation factor (MyD88), interferon regulatory factor-7 (IRF-7) in synovial tissue of rabbits in each group. Results:Compared with model group, the pain threshold of rabbits in heat supplementing needles group, Lijin Zhenggu Therapy group and combination group increased ( P<0.05); the levels of PGE 2 and IL-1β decreased ( P<0.05), while the level of β-EP increased ( P<0.05). LXRα mRNA level increased ( P<0.05), and NF-κB mRNA level decreased ( P<0.05); the expressions of TLR4, MyD88, IRF-7 and NF-κB P65 in synovial tissue decreased ( P<0.05). Conclusions:Lijin Zhenggu Therapy combined with heat supplementing needles can reduce the levels of PGE 2 and IL-1β, increase β-EP level, improve pain and cartilage tissue morphology. The mechanism may be related to the regulation of liver X receptor nuclear factor NF-κB pathway, reduction of inflammatory reactions and immunity maintaining.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:Type H blood vessels are a subtype of bone-specific microvessels(CD31hiEmcnhi)that play an important regulatory role in the coupling of angiogenesis and osteogenesis.Despite reports on the distinct roles of type H and L vessels under physiological and pathological bone conditions,their genetic differences remain to be elucidated.This study aims to construct a competitive endogenous RNA(ceRNA)network of key gene for differencial expression(DE)in type H and L vascular endothelial cells(ECs)through integrated bioinformatic methods. Methods:We downloaded relevant raw data from the ArrayExpress and the Gene Expression Omnibus(GEO)database and used the Limma R-Bioconductor package to screen for DE lncRNAs,DE miRNAs,and DE mRNAs between type H and L vascular ECs.A total ceRNA network was constructed based on their interactions,followed by refinement using protein-protein interaction(PPI)networks to select upregulated and downregulated key genes.Enrichment analysis was performed on these key genes.Random validation was conducted using flow cytometry and real-time RT-PCR. Results:A total of 1 761 DE mRNAs,187 DE lncRNAs,and 159 DE miRNAs were identified,and a comprehensive ceRNA network was constructed based on their interactions.Six upregulated(Itga5,Kdr,Tjp1,Pecam1,Cdh5,and Ptk2)and 2 downregulated(Csf1r and Il10)key genes were selected via PPI network to construct a subnetwork of ceRNAs related to these key genes.Upregulated key genes were mainly enriched in negative regulation of angiogenesis and vascular apoptosis.Results from flow cytometry and real-time RT-PCR were consistent with bioinformatics analysis. Conclusion:This study proposes a ceRNA network associated with upregulated and downregulated type H and L vascular ECs based on selected key genes,providing new insights into the regulatory mechanisms of type H and L vascular ECs in bone metabolism.

Objective:The antimicrobial resistance of Staphylococcus aureus(S.aureus)has become a challenge in the treatment of infectious diseases.It is of great clinical value to discovery effective antimicrobial agents against multi-drug resistant S.aureus and its biofilms.This study aims to explore the antibacterial activity of the antiparasitic drug closantel against methicillin-resistant S.aureus and its biofilms through drug repurposing. Methods:The sensitivity of S.aureus to closantel was assessed using microbroth dilution and disk diffusion methods.The bacteriostatic and bactericidal activities of closantel were determined by time-kill curves and colony count.Scanning electron microscopy combined with SYTOX Green and DiSC3(5)fluorescence probes were used to study the bactericidal mechanism of closantel.The influence of resistance was assessed by continuous exposure to sub-inhibitory concentrations of closantel.The anti-biofilm activity was evaluated using 96-well plates and crystal violet staining,and cytotoxicity was measured using the CCK-8 assay. Results:The minimal inhibitory concentration(MIC)of closantel for both methicillin-sensitive and methicillin-resistant S.aureus ranged from 0.125 to 1.000 μg/mL.Disk diffusion tests showed that 80 pg of closantel created an inhibition zone,which increased in diameter with higher drug amounts.Sub-inhibitory concentrations(0.031 μg/mL)of closantel significantly inhibited S.aureus proliferation,reducing bacterial turbidity from 0.26±0.00 to 0.11±0.01(t=16.06,P＜0.001),with stronger inhibition at higher concentrations.Closantel at 0.25×MIC inhibited S.aureus proliferation for 12 hours,while lxMIC inhibited it for over 24 hours,with the number of viable bacteria decreasing as the drug concentration increased.Mechanistic studies indicated that closantel effectively disrupted the integrity of S.aureus cell membranes,significantly increasing SYTOX Green and DiSC3(5)fluorescence intensity.Even after 25 days of continuous exposure to sub-inhibitory concentrations of closantel,no resistance developed.Closantel at 0.0625 μg/mL significantly inhibited biofilm formation,reducing it from 1.29±0.16 to 0.62±0.04(t=11.62,P＜0.001),showing a clear dose-dependent effect.Closantel at 2 μg/mL also significantly eradicated established biofilms,reducing biofilm mass from 1.62±0.34 to 0.51±0.39(t=4.84,P＜0.01).Additionally,closantel exhibited extremely low cytotoxicity,with half-maximal lethal concentrations for HepG2 liver cancer cells and normal LO2 liver cells both exceeding 64 μg/mL. Conclusion:Closantel exhibits strong antibacterial activity against S.aureus and its biofilm with low cytotoxicity against human cells,making it a promising candidate for new therapeutic strategies against S.aureus-related infections.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.