Anterior Shoulder Stabilization Using Single Needle-Assisted Outside-In Remplissage Technique and Bankart Repair.

Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail.

Physeal-Sparing, All-Inside Anterior Cruciate Ligament Reconstruction Using Quadrupled Semitendinosus Autograft and Suture Tape Augmentation for Skeletally Immature Patients.

The anterior cruciate ligament (ACL) is the primary soft-tissue structure for anterior stabilization of the knee and is one of the most frequently injured structures. The incidence of ACL injuries in children and adolescents ranges from 92 to 151 per 100,000 person-years. The choice of surgical treatment for this population group is controversial, with a widespread concern that adult reconstruction techniques may damage the epiphyseal plate, compromise growth, or cause deformity. In this article, we describe a physeal-sparing, all-inside ACL reconstruction technique for skeletally immature patients. This technique is supported by retrograde drilling of the femoral tunnel and retrograde drilling of the tibial tunnel, both of which are able to avoid the epiphyseal growth line. Fixation of the quadrupled semitendinosus autograft and suture tape augmentation are achieved by soft-tissue buttons on the femur and tibia. The surgical details of this reproducible reconstruction technique are elaborated.

Long-term effects of exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear: A meta-analysis of randomized controlled trials.

BACKGROUND: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression. RESULTS: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods. CONCLUSION: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM.

Appropriate thromboprophylaxis strategy for COVID-19 patients on dosage, antiplatelet therapy, outpatient and post-discharge prophylaxis: a meta-analysis of randomized controlled trials.

BACKGROUND: There was controversy surrounding the optimal thromboprophylaxis strategy for COVID-19 patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and post-discharge. To explore this, we performed a meta-analysis of randomized controlled trials. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet and post-discharge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. RESULTS: Our study included a total of 25 randomized controlled trials, involving 17,911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95%CI, 0.45 to 0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For non-critically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95%CI 0.34 to 0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95%CI 1.22 to 3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95%CI 0.21 to 0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For post-discharge patients, post-discharge prophylaxis reduced thromboembolism risk (RR, 0.49; 95%CI 0.31 to 0.76) but increased major bleeding risk (RR, 2.63; 95%CI, 1.13 to 6.14). CONCLUSION: For non-critically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and post-discharge patients, required further investigation and confirmation through rigorous evidence studies.

Interposition Grafting Using Fascia Lata Autograft for Failed Rotator Cuff Repairs.

Massive rotator cuff tears are a huge challenge for orthopaedic surgeons, as the patients may be in need of multiple operations, even including reverse total shoulder arthroplasty. The various repair methods for the rotator cuff, such as partial rotator cuff repair, patch-augmented rotator cuff repair, bridging rotator cuff reconstruction with graft interposition, tendon transfer, and superior capsular reconstruction, have always been the focus of research. During surgical intervention for failed rotator cuff repairs, complexity of tears, poor tissue quality, retained hardware, and adhesions are the problems routinely encountered. In this Technical Note, we describe the technique of interposition grafting using fascia lata autograft to reconstruct the rotator cuff after failed primary repair.

Preferences in anterior cruciate ligament reconstruction: A survey among orthopedic surgeons in China.

The purpose of this study was to reveal the current trends and preferences of Chinese orthopedic surgeons regarding anterior cruciate ligament (ACL) reconstruction through a nationwide web-based survey conducted in China. The survey questionnaire was distributed via WeChat to the chairmen of provincial orthopedic and sports medicine organizing committees in China, who then shared it in their respective WeChat workgroups. The questionnaire consisted of 52 multiple-choice questions covering 8 sections. Data collection was implemented by Questionnaire Star. A total of 812 valid questionnaires were returned: 94.21% of the respondents preferred single-bundle reconstruction of ACL, while 61.70% preferred autogenous semitendinosus plus gracilis reconstruction; 76.35% of the respondents preferred establishing the femoral tunnel first, while 47.29% preferred establishing the femoral tunnel through a medial auxiliary approach; and 85.10% of the respondents recommended patients to undergo surgery within 3 months after ligament injury. Besides, the vast majority of respondents chose to retain the ligamentous remnant bundle (92.98%) and recommended routine use of knee braces postoperatively (94.09%). It is recommended to perform arthroscopic single-bundle ACL reconstruction with the remnant preserving technique using a hamstring autograft within 3 months of ACL rupture, with support of postoperative functional braces.

Identification and subtype analysis of biomarkers associated with the solute carrier family in acute myocardial infarction.

The dysregulation of some solute carrier (SLC) proteins has been linked to a variety of diseases, including diabetes and chronic kidney disease. However, SLC-related genes (SLCs) has not been extensively studied in acute myocardial infarction (AMI). The GSE66360 and GSE60993 datasets, and SLCs geneset were enrolled in this study. Differentially expressed SLCs (DE-SLCs) were screened by overlapping DEGs between the AMI and control groups and SLCs. Next, functional enrichment analysis was carried out to research the function of DE-SLCs. Consistent clustering of samples from the GSE66360 dataset was accomplished based on DE-SLCs selected. Next, the gene set enrichment analysis (GSEA) was performed on the DEGs-cluster (cluster 1 vs cluster 2). Three machine learning models were performed to obtain key genes. Subsequently, biomarkers were obtained through receiver operating characteristic (ROC) curves and expression analysis. Then, the immune infiltration analysis was performed. Afterwards, single-gene GSEA was carried out, and the biomarker-drug network was established. Finally, quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of biomarkers. In this study, 13 DE-SLCs were filtered by overlapping 366 SLCs and 448 DEGs. The functional enrichment results indicated that the genes were implicated with amino acid transport and TNF signaling pathway. After the consistency clustering analysis, the samples were classified into cluster 1 and cluster 2 subtypes. The functional enrichment results showed that DEGs-cluster were implicated with chemokine signaling pathway and so on. Further, SLC11A1 and SLC2A3 were identified as SLC-related biomarkers, which had the strongest negative relationship with resting memory CD4 T cells and the strongest positive association with activated mast cells. In addition, the single-gene GSEA results showed that cytosolic ribosome was enriched by the biomarkers. Five drugs targeting SLC2A3 were predicted as well. Lastly, the experimental results showed that the biomarkers expression trends were consistent with public database. In this study, 2 SLC-related biomarkers (SLC11A1 and SLC2A3) were screened and drug predictions were carried out to explore the prediction and treatment of AMI.

The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D (VitD) has been shown to be important for the immune response of the respiratory system, but the preventive and therapeutic effects of vitamin D supplementation on SARS-CoV-2 infection are controversial. This study aimed to determine the role of vitamin D supplementation in the prevention and treatment of SARS-CoV-2 infection through a meta-analysis of randomized controlled trials. METHODS: The databases of PubMed, Cochrane Library, Embase, Web of Science and Google Scholar were searched systematically from inception to April 17,2023 to identify trials involving a randomized comparison of vitamin D supplementation versus non-vitamin D supplementation for SARS-CoV-2 infection prevention or treatment. RESULTS: We retrieved 25 eligible trials, including 8128 participants. Four trials compared the preventive effects of vitamin D supplementation on SARS-CoV-2 infection, and the results (RR 0.31; 95%CI 0.07 to 1.32) were inconclusive. Regarding the treatment of SARS-CoV-2 infection with vitamin D supplementation, it was found that vitamin D supplementation could significantly reduce the rates of ICU admission (RR 0.63; 95%CI 0.44 to 0.89) and mechanical ventilation (RR 0.58; 95%CI 0.39 to 0.84), but had no statistically significant effect on mortality. However, in subgroup analyses based on the patients' specific conditions, vitamin D supplementation significantly reduced the mortality in patients with vitamin D deficiency (RR 0.76; 95%CI 0.58 to 0.98). CONCLUSION: Vitamin D supplementation may have some beneficial impact on the severity of illness caused by SARS-CoV-2, particularly in VitD deficient patients, but further studies are still needed.

Slowed Intestinal Transit Induced by Less Mucus in Intestinal Goblet Cell Piezo1-Deficient Mice through Impaired Epithelial Homeostasis.

Mucus secreted by goblet cells (GCs) may play an important role in intestinal transit function. Our previous study found that Piezo1 protein is essential for GC function; however, the effect of GC Piezo1 on intestinal transit function is unclear. Our study aimed to investigate the effect of Piezo1 in GCs on intestinal transit and the potential mechanism. We compared intestinal mucus, fecal form, intestinal transit time, intestinal epithelial cell composition, and stem cell function in WT and GC-specific Piezo1-deficient (Piezo1ΔGC) mice. Our results revealed a correlation between mucus and intestinal transit: the less mucus there was, the slower the intestinal transit. Piezo1 deficiency in GCs led to decreased mucus synthesis and also disrupted the ecological niche of colon stem cells (CSCs). Through organoid culture, we found that the capacity of proliferation and differentiation in Piezo1ΔGC mouse CSCs was significantly decreased, which also led to a reduced source of GCs. Further studies found that the reduced Wnt and Notch signals in colon crypts might be the potential mechanism. These results indicated the importance of GC Piezo1 in intestinal transit function, which acts by maintaining the homeostasis of intestinal epithelial cells and mucus.

Exploring Restrictions to use of community greenways for physical activity through structural equation modeling.

Public health problems caused by rapid urbanization have attracted increasing amounts of attention. Existing studies show that improving the frequency and duration of physical activity among urban residents can effectively reduce their disease risk. A community greenway, as a green space for public activity directly serving community residents, is one of the best spatial place for bringing health benefits to people. Although the scale and scope of greenway construction have been increasing in recent years, the utilization rate of some greenways is not high for various reasons, restricting the extent to which people engage in healthy physical activities in greenway spaces. In this study, the greenway of Nancheng Community in Wenjiang District, Chengdu city, China was selected as the object of study, and structural equation modeling was conducted to explore the objective environmental factors and individual characteristics acting as barriers to use of the community greenway by the population for physical activity. The results show that user experience, the greenway landscape, and safety and accessibility are important factors that restrict people's willingness engage in physical activity in the community greenway environment. The results of this study provide a direction for further consideration of ways to enhance people's willingness to make use of greenways for physical activity, and further provide a theoretical basis for the healthy design and transformation of community greenway spaces.

Receptor Tyrosine Kinase: Still an Interesting Target to Inhibit the Proliferation of Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) proliferation is a critical event that contributes to the pathogenesis of vascular remodeling such as hypertension, restenosis, and pulmonary hypertension. Increasing evidences have revealed that VSMCs proliferation is associated with the activation of receptor tyrosine kinases (RTKs) by their ligands, including the insulin-like growth factor receptor (IGFR), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR). Moreover, some receptor tyrosinase inhibitors (TKIs) have been found and can prevent VSMCs proliferation to attenuate vascular remodeling. Therefore, this review will describe recent research progress on the role of RTKs and their inhibitors in controlling VSMCs proliferation, which helps to better understand the function of VSMCs proliferation in cardiovascular events and is beneficial for the prevention and treatment of vascular disease.

Computer-Assisted and Hip Arthroscopy for Avascular Necrosis of the Femoral Head With Femoroacetabular Impingement.

Avascular necrosis of the femoral head with femoroacetabular impingement is a disabling disease. Without early treatment and intervention, its further development will even lead to hip osteoarthritis and hip dysfunction. This technical note aims to introduce a computer-assisted precise core decompression of the femoral head, followed by injection of platelet-rich plasma and bone marrow aspirate concentrate. Then, the autologous ipsilateral iliac bone is transplanted to the core decompression area. Thereafter, under hip arthroscopy, the injured glenoid lip of the hip joint is repaired, and the cam deformity of the femoral head/neck junction is polished and formed. The advantages of this technique include accurately locating the core decompression area, combined with autologous cells and bone transplantation, being able to delay the process of avascular necrosis of the femoral head, and evaluating articular cartilage injury, subchondral collapse, and guidance during reaming and curettage.

The association of melatonin use and hip fracture: a matched cohort study.

By using propensity-score matched cohorts, we compared the risk of incident hip fracture between melatonin initiators and hypnotic benzodiazepines initiators. The initiation of melatonin was not associated with an increased risk of hip fracture. INTRODUCTION: Melatonin is hypothesized to suppress bone loss, but a previous study reported an increased risk of hip fracture among melatonin users compared with non-users, which was however susceptible to confounding by indication. This study aimed to compare the risk of hip fracture between melatonin initiators and initiators of its active comparators, i.e., hypnotic benzodiazepines. METHODS: Among individuals aged 40 years or older without a history of hip fracture or cancer in the IQVIA Medical Research Database (IMRD) in the UK (2000-2018), a propensity score-matched cohort study was conducted to examine the association of melatonin initiation vs. hypnotic benzodiazepines initiation with the risk of hip fracture. RESULTS: After propensity score matching, 9,038 patients were included (4,519 melatonin initiators and 4,519 hypnotic benzodiazepines initiators). During the entire follow-up, 41 cases of hip fracture occurred in the melatonin cohort, and 51 cases occurred in the hypnotic benzodiazepines cohort. The absolute rate difference in hip fracture between melatonin initiators and hypnotic benzodiazepines initiators was -0.8 (95% CI: -1.9 to 0.3) per 1000 person-years and the multivariable-adjusted hazard ratio (HR) of hip fracture for melatonin initiators was 0.78 (95% CI: 0.51 to 1.17). CONCLUSION: In this population-based cohort study, the risk of hip fracture among melatonin initiators was not higher, if not lower, than that among hypnotic benzodiazepines initiators.

Editorial Commentary: Hip Arthroscopy in Patients With Moderate to Advanced Osteoarthritis Shows Unpredictable Results.

Hip arthroscopy is an effective surgical approach for the treatment of femoroacetabular impingement (FAI) syndrome with concomitant mild hip osteoarthritis (OA). However, in the FAI patients with moderate to advanced hip OA (Tönnis grade 2 or greater), whether hip arthroscopy could provide symptomatic relief or delay the need for an ultimate total hip arthroplasty surgery is controversial. The literature is heterogeneous and of generally lower quality evidence. Recent research reporting 10-year outcomes of hip arthroscopy in patients with hip OA shows 57% survivorship, and 78% survivor satisfaction. With unpredictable results, surgeons and well informed patients could hold some hope for a positive outcome after arthroscopy of an arthritic hip. As the Tönnis grading system shows poor interobserver reliability, surgeons may need to carefully consider their personal indications and resultant outcomes.

Activation of goblet cell Piezo1 alleviates mucus barrier damage in mice exposed to WAS by inhibiting H3K9me3 modification.

BACKGROUND: Our recent studies found that intestinal mechanical signals can regulate mucus synthesis and secretion of intestinal goblet cells through piezo type mechanosensitive ion channel component 1 (Piezo1), but the detailed molecular mechanisms remain to be investigated. Previous studies using a water avoidance stress (WAS) model reported decreased intestinal mucus accompanied by abnormal intestinal motility. It has also been reported that the expression of mucin2 was negatively correlated with histone H3 lysine 9 trimethylation (H3K9me3), a key regulator of histone methylation, and that mechanical stimulation can affect methylation. In this study, we aimed to determine whether and how Piezo1 expressed on goblet cells regulates mucus barrier function through methylation modification. METHODS: A murine WAS model was established and treated with Yoda1 (Piezo1 agonist), and specific Piezo1 flox-mucin2 Cre mice were also tested. The mucus layer thickness and mucus secretion rate of mouse colonic mucosa were detected by a homemade horizontal Ussing chamber, intestinal peristaltic contraction was detected by the ink propulsion test and organ bath, goblet cells and mucus layer morphology were assessed by HE and Alcian blue staining, mucus permeability was detected by FISH, and the expression levels of Piezo1, H3K9me3 and related molecules were measured by Western blots and immunofluorescence. LS174T cells were cultured on a shaker board in vitro to simulate mechanical stimulation. Piezo1 and H3K9me3 were inhibited, and changes in mucin2 and methylation-related pathways were detected by ELISAs and Western blots. ChIP-PCR assays were used to detect the binding of H3K9me3 and mucin2 promoters under mechanical stimulation. RESULTS: Compared with those of the controls, the mucus layer thickness and mucus secretion rate of the mice exposed to WAS were significantly decreased, the mucus permeability increased, the number of goblet cells decreased, and the intestinal contraction and peristalsis were also downregulated and disordered. Intraperitoneal injection of Yoda1 improved mucus barrier function and intestinal contraction. In the colonic mucosa of mice exposed to WAS, Piezo1 was decreased, and histone H3 lysine 9 trimethylation (H3K9me3) and methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39h1) were increased, but activating Piezo1 alleviated these effects of WAS. Piezo1 flox-mucin2 Cre mice showed decreased mucus expression and increased methylation compared to wild-type mice. Cell experiments showed that mechanical stimulation induced the activation of Piezo1, decreased H3K9me3 and SUV39h1, and upregulated mucin2 expression. Inhibition of Piezo1 or H3K9me3 blocked the promoting effect of mechanical stimulation on LS174T mucin2 expression. The binding of H3K9me3 to the mucin2 promoter decreased significantly under mechanical stimulation, but this could be blocked by the Piezo1 inhibitor GsMTx4. CONCLUSION: Piezo1 mediates mechanical stimulation to inhibit SUV39h1, thereby reducing H3K9me3 production and its binding to the mucin2 promoter, ultimately promoting mucin2 expression in goblet cells. This study further confirmed that piezo1 on goblet cells could regulate mucus barrier function through methylation.

ACL stump and ACL femoral landmarks are equally reliable in ACL reconstruction for assisting ACL femoral tunnel positioning.

PURPOSE: This study aimed to comparatively evaluate the accuracy of femoral tunnel positioning after anatomic single-bundle anterior cruciate ligament (ACL) reconstruction performed with the remnant preservation (RP) technique versus the non-remnant preservation (NRP) technique. METHODS: A retrospective review of 145 patients who underwent ACL reconstruction from May 2020 to May 2022 were performed in this single-surgeon study. A total of 120 patients met the inclusion criteria and were allocated into two groups according to the surgical technique (i.e. RP group and NRP group). The relative location of the femoral tunnel in the lateral condyle was evaluated as a percentage using a standardized grid system on the three-dimensional computed tomography (3D-CT) image. The accuracy and precision of the RP group were assessed based on published anatomical data in direct comparison with the NRP group. RESULTS: According to the surgical procedure, 57 of the 120 patients included were allocated into the RP group, and 63 into the NRP group. Significant differences were observed between the two groups in terms of tunnel position (posterior-to-distal (PD): 28.4 ± 5.4% (RP) vs. 31.8 ± 5.3% (NRP); P = 0.01), (anterior-to-posterior (AP): 32.6 ± 7.7% (RP) vs. 38.8 ± 7.7% (NRP); P = 0.00), while no significant differences were found in terms of the accuracy (8.6% (RP) vs. 8.9% (NRP); n.s) and precision (4.4% (RP) vs. 5.6% (NRP); n.s) of femoral tunnel positioning between the two groups. CONCLUSIONS: From this single-surgeon study, it was concluded that there were no differences in the creation of ACL femoral tunnel between the RP technique and the non-remnant preserving technique. Meanwhile, the RP technique would not sacrifice the ideal position of the femoral tunnel and is able to retain the possible benefits of the ACL stump. LEVEL OF EVIDENCE: Level III.

Efficacy and Safety of Tramadol for Knee or Hip Osteoarthritis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To examine efficacy and safety of tramadol for knee or hip osteoarthritis (OA). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched up to May 2020 for randomized controlled trials (RCTs) comparing any of the following interventions: tramadol 100 mg/day, 200 mg/day, and 300 mg/day, and placebo for knee or hip OA. Pain and function were measured at or near 12 weeks for efficacy. Gastrointestinal, cardiovascular, and central nervous system (CNS) adverse events (AEs), and withdrawals were measured for safety. Bayesian network meta-analysis was conducted. RESULTS: Six RCTs (3,611 participants) were included. Tramadol 100 mg/day (standardized mean difference [SMD] -0.16 [95% confidence interval (95% CI) -0.34, 0.00]), 200 mg/day (SMD -0.21 [95% CI -0.37, -0.06]), and 300 mg/day (SMD -0.30 [95% CI -0.48, -0.14]) were statistically more effective than placebo in pain relief, but only tramadol 300 mg/day was better than placebo in functional improvement (SMD -0.24 [95% CI -0.47, -0.03]). Tramadol 100 mg/day (relative risk [RR] 2.29 [95% credible interval (CrI) 1.22, 4.25]), 200 mg/day (RR 4.35 [95% CrI 2.31, 8.01]), and 300 mg/day (RR 6.02 [95% CrI 3.22, 11.1]) involved a higher risk of gastrointestinal AEs. Similarly, tramadol 100-300 mg/day showed a higher risk of CNS AEs and withdrawals. However, the risk of cardiovascular AEs remained unclear. CONCLUSION: Only tramadol 300 mg/day showed minimal improvement in pain and function but with increasing AEs compared with placebo. Tramadol may not be sufficiently recommended for knee or hip OA based on the presented evidence, especially in patients with the risk of gastrointestinal and CNS AEs.

Anterior cruciate ligament tear increases the risk of venous thromboembolism: a population-based cohort study.

PURPOSE: Previous studies highlighted an increased risk of venous thromboembolism (VTE) among patients with anterior cruciate ligament reconstruction (ACLR); however, the risk for those with ACL tear but without undergoing ACLR has not been reported yet. The aim of this study was to evaluate the risk of VTE among ACL tear individuals with or without ACLR derived from the general population. METHODS: A cohort study was conducted using data from the IQVIA Medical Research Database of the United Kingdom. Up to five non-ACL tear individuals (n = 22,235) were matched to each case of ACL tear (n = 4474) by age, sex, body mass index and entry-time. The relation of ACL tear to VTE [pulmonary embolism (PE) and deep vein thrombosis (DVT)] was examined using a multivariable Cox proportional hazard model. A sub-cohort analysis, in which the ACL tear individuals were stratified into those with ACLR and those without ACLR, was also conducted. RESULTS: VTE developed in 13 individuals with ACL tear and nine individuals without ACL tear (incidence rates: 3.1 vs. 0.4/1000 person-years), with multivariable-adjusted hazard ratio (HR) being 6.59 (95% CI 2.28-19.08) in 1-year follow-up. For ACL tear individuals with ACLR, the HR was 11.44 (95% CI 2.71-48.28), and for those without ACLR, the HR was 6.02 (95% CI 1.44-24.25), compared with individuals without ACL tear. CONCLUSION: This large-sample population-based cohort study provides the first evidence on an increased risk of VTE in ACL tear individuals regardless of subsequent ACLR, which supports the necessity for monitoring venous-thromboembolic complications in the target population, including those without ACLR. LEVEL OF EVIDENCE: III.

Reprogrammed fecal and mucosa-associated intestinal microbiota and weakened mucus layer in intestinal goblet cell- specific Piezo1-deficient mice.

Dysfunction of the mucus layer allows commensal and pathogenic microorganisms to reach the intestinal epithelium, thereby leading to infection and inflammation. This barrier is synthesized and secreted by host goblet cells. Many factors that influence the function of goblet cells (GCs) have been studied. However, how the microenvironment surrounding GCs influences the mucus layer and microbiota of the colon is unclear. To explore the effect of GC Piezo1 on the mucus layer and microbiota in the colon, we generated an intestinal epithelial Piezo1 conditional knockout mouse model. The fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) of the two groups were characterized based on amplicon sequencing of the 16S rRNA gene. Our results showed that GC Piezo1-/- mice developed decreased GC numbers, thinner mucus layer, and increased inflammatory cytokines (e.g., CXCL1, CXCL2, IL-6) on the 7th day. In addition, decreased Spdef and increased DOCK4 were discovered in KO mice. Meanwhile, the diversity and richness were increased in MAM and decreased in FAM in the GC Piezo1-/- group compared with the GC Piezo1+/+ group. We also observed increased abundances of Firmicutes and decreased abundances of Verrucomicrobiota and Actinobacteriota in the MAM of the GC Piezo1-/- group. Additionally, BugBase predicts that potentially pathogenic bacteria may have increased in the inner mucus layer, which is consistent with the higher abundance of Helicobacter hepaticus, Lactobacillus johnsonii, Escherichia-Shigella and Oscillospiraceae in MAM. These results further support the hypothesis that the role of Piezo1 in GCs is important for maintaining the function of the mucus layer and intestinal microbiota balance in the mouse colon.

Current status of immunotherapy for non-small cell lung cancer.

Nowadays, lung cancer is still the deadliest oncological disease in the world. Among them, non-small cell lung cancer (NSCLC) accounts for 80%∼85% of all lung cancers, and its 5-year survival rate is less than 15%, making the situation critical. In the past decades, despite some clinical advances in conventional treatments, the overall survival rate of NSCLC is still not optimistic due to its unique physiological conditions and the frequent occurrence of tumor escape. In recent years, immunotherapy has become a new hot spot in lung cancer research, including antibody therapy and cell therapy, which have been developed and utilized one after another, especially immune checkpoint inhibitor (ICI). These approaches have effectively improved the overall survival rate and objective response rate of NSCLC patients by enhancing the immune capacity of the body and targeting tumor cells more effectively, which is more specific and less toxic compared with conventional chemotherapy, and providing more strategies for NSCLC treatment. In this paper, we reviewed the relevant targets, clinical progress and adverse reaction in monoclonal antibodies, antibody-drug conjugates, ICI, bispecific antibodies, T-cell receptor engineered T cell therapy (TCR-T), Chimeric antigen receptor T-cell immunotherapy (CAR-T), and also report on their combination therapy from the immune-related background to provide better NSCLC treatment and prospective.