Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis.

Objective: To evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC). Method: Articles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs). Results: Totally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77). Conclusion: Our results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.

Biomechanical evaluation of ortho-bridge system and proximal femoral nail antirotation in intertrochanteric fractures with lateral wall fracture based on finite element analysis.

Background: The integrity of the lateral wall in femoral intertrochanteric fractures significantly impacts fracture stability and internal fixation. In this study, we compared the outcomes of treating intertrochanteric fractures with lateral wall involvement using the ortho-bridge system (OBS) combined with proximal femoral nail antirotation (PFNA) versus simple PFNA from a biomechanical perspective. Methods: Finite-element models of femoral intertrochanteric fractures with lateral wall involvement were subjected to fixation with OBS combined with PFNA and simple PFNA. Von Mises stress measurements and corresponding displacement assessments for each component of the model, including the proximal femur and lateral wall, were used to evaluate the biomechanical effects of OBS fixation on bone and intramedullary nail stability. Results: Using PFNA alone to fix intertrochanteric fractures with lateral wall involvement resulted in von Mises stress levels on the lateral wall exceeding safe stress tolerances for bone growth. OBS fixation significantly reduced stress on the lateral wall of the femur and minimized the stress on each part of the intramedullary nail, reducing the overall displacement. Conclusion: In cases of intertrochanteric fractures with lateral wall involvement, PFNA fixation alone may compromise the biomechanical integrity of the lateral femoral wall, increasing the risk of postoperative complications. The addition of OBS to PFNA significantly reduces stress on the lateral femoral wall. Consequently, OBS should be considered for lateral wall fixation when managing intertrochanteric fractures combined with lateral wall fractures.

Allergic diseases and Meniere's disease: a bidirectional Mendelian randomization.

OBJECTIVES: Allergic diseases and Meniere's disease found to have a possible link in observational study. However, the potential causal relationship between the two is unclear. Therefore, we aimed to explore the causal relationship between allergic diseases and Meniere's disease using a new data analysis technique called bidirectional Mendelian randomization study. METHOD: Summary-level statistics for Meniere's disease and three allergic diseases (asthma, allergic rhinitis, eczema/dermatitis) were obtained from large-scale genome-wide association studies. The inverse variance weighted method was used as the primary measure, supplemented by MR-Egger regression and the weighted median method. To ensure the reliability of the conclusions, Cochran's Q, MR-Egger intercept, MR-PRESSO test, leave-one-out test, and MR Steiger test were used. RESULTS: Inverse-variance weighted method showed asthma (p = 0.008, OR = 3.908, 95% CI 1.424-10.724, adjust_p = 0.024), allergic rhinitis (p = 0.026, OR = 24.714, 95% CI 1.479-412.827, adjust_p = 0.026) and eczema/dermatitis (p = 0.019, OR = 3725.954, 95% CI 3.795 to 3,658,399.580, adjust_p = 0.029) all had a significant effect on Meniere's disease. Reverse Mendelian randomization studies have shown that Meniere's disease does not increase the risk of three allergic diseases. Sensitivity analysis showed no horizontal pleiotropy and heterogeneity for each trait. CONCLUSION: Our Mendelian randomization analysis supports a positive causal relationship between three allergic diseases (asthma, allergic rhinitis, eczema/dermatitis) and Meniere's disease. This suggests that physicians should pay more attention to the Meniere's patient's allergy history and consider allergy avoidance as part of their treatment plan. LEVEL OF EVIDENCE: Mendelian Randomized (MR) studies are second only to randomized controlled trials in terms of the level of evidence.

Comparative long-term outcomes of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy as first-line therapy for metastatic non-small-cell lung cancer: a systematic review and network meta-analysis.

Introduction: This systematic review and network meta-analysis(NMA) was designed to compare the long-term outcomes of pembrolizumab monotherapy and pembrolizumab plus chemotherapy as first-line therapy for metastatic non-small-cell lung cancer(NSCLC). Materials and Methods: Four databases(Medline, Embase, Web of Science and CENTRAL were searched published from establishment of database to August 17, 2023, for articles studying pembrolizumab monotherapy or pembrolizumab plus chemotherapy for non-small cell lung cancer (NSCLC). Network meta-analyses of progression-free survival(PFS), overall survival(OS), objective response rate(ORR), treatment-related adverse events(trAEs) and immune-related adverse events(irAEs) were performed. Results: A total of five studies were considered for NMA. This NMA includes a cohort of 2878 patients diagnosed with advanced NSCLC. Among them, 791 patients received pembrolizumab monotherapy, 1337 patients received chemotherapy, and 748 patients received pembrolizumab plus chemotherapy. The IPDformKM software was utilized to reconstruct Kaplan-Meier curves for OS and PFS, offering a lucid and intuitive depiction of oncological outcomes. For patients who have high levels of programmed death-ligand 1(PD-L1) expression (≥50%), pembrolizumab plus chemotherapy was more effective than using pembrolizumab alone as first-line therapy in terms of PFS (median survival time: 10.41 months versus 7.41 months, HR: 0.81, 95%CI 0.67 to 0.97, P=0.02) and ORR (RR:1.74, 95% CI: 1.25-2.43). Nevertheless, there was no statistically significant difference observed between the two groups in terms of OS (median survival time: 22.54 months versus 22.62 months, HR: 0.89, 95%CI 0.73 to 1.08, P=0.24). Furthermore, pembrolizumab plus chemotherapy provided a more advantageous long-term survival advantage in terms of OS (median survival time: 20.88 months versus 13.60 months, HR: 0.77, 95%CI: 0.62 to 0.95, P=0.015) compared to pembrolizumab monotherapy in patients with low PD-L1 expression levels (1% to 49%). With regards to safety, there was no statistically significant disparity between the two groups in relation to any irAEs (RD=0.02, 95% CI: -0.12 to 0.16) or Grade≥ 3 irAEs (RD=0.01, 95% CI: -0.10 to 0.12). Nevertheless, pembrolizumab plus chemotherapy exhibited a greater likelihood of encountering any trAEs (RD=0.23, 95% CI: 0.17 to 0.30) and Grade≥ 3 trAEs (RD=0.28, 95% CI: 0.21 to 0.35) in comparison to pembrolizumab monotherapy. Conclusions: The present network meta-analysis reported comparative long-term outcomes of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy as first-line therapy for metastatic non-small-cell lung cancer. Pembrolizumab plus chemotherapy led to improved PFS and ORR in patients with advanced NSCLC who had a PD-L1 expression level of 50% or above. However, there was no noticeable benefit in terms of OS when pembrolizumab was paired with chemotherapy compared to utilizing pembrolizumab alone. In addition, pembrolizumab plus chemotherapy offered a greater long-term survival benefit in terms of OS when compared to utilizing pembrolizumab alone in patients with PD-L1 expression levels ranging from 1% to 49%. Furthermore, the increased effectiveness of pembrolizumab plus chemotherapy was accompanied by an increase in adverse side effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024501740.

Efficacy and safety of robot-assisted deep brain stimulation for Parkinson's disease: a meta-analysis.

Objective: This meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson's disease(PD). Methods: Four databases (Medline, Embase, Web of Science and CENTRAL) were searched from establishment of database to 23 March 2024, for articles studying robot-assisted DBS in patients diagnosed with PD. Meta-analyses of vector error, complication rate, levodopa-equivalent daily dose (LEDD), Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, and UPDRS IV were performed. Results: A total of 15 studies were included in this meta-analysis, comprising 732 patients with PD who received robot-assisted DBS. The pooled results revealed that the vector error was measured at 1.09 mm (95% CI: 0.87 to 1.30) in patients with Parkinson's disease who received robot-assisted DBS. The complication rate was 0.12 (95% CI, 0.03 to 0.24). The reduction in LEDD was 422.31 mg (95% CI: 68.69 to 775.94). The improvement in UPDRS, UPDRS III, and UPDRS IV was 27.36 (95% CI: 8.57 to 46.15), 14.09 (95% CI: 4.67 to 23.52), and 3.54 (95% CI: -2.35 to 9.43), respectively. Conclusion: Robot-assisted DBS is a reliable and safe approach for treating PD. Robot-assisted DBS provides enhanced accuracy in contrast to conventional frame-based stereotactic techniques. Nevertheless, further investigation is necessary to validate the advantages of robot-assisted DBS in terms of enhancing motor function and decreasing the need for antiparkinsonian medications, in comparison to traditional frame-based stereotactic techniques.Clinical trial registration: PROSPERO(CRD42024529976).

Efficacy and safety of robotic radical hysterectomy in cervical cancer compared with laparoscopic radical hysterectomy: a meta-analysis.

Introduction: Robotic radical hysterectomy (RRH) is a newly developed minimally invasive surgery that has been suggested as a substitute for laparoscopic radical hysterectomy (LRH). This meta-analysis aims to assess the clinical efficacy and safety of robot-assisted radical hysterectomy (RRH) for cervical cancer. Materials and methods: A systematic search was conducted in four databases (Medline, Embase, Web of Science, and CENTRAL) for studies comparing the utilization of RRH and LRH in the treatment of cervical cancer. The search included articles published from the inception of the databases up until July 18, 2023. Meta-analyses were conducted to assess several surgical outcomes, including operation time, estimated blood loss, length of hospital stay, pelvic lymph nodes, positive surgical margin, total complications, one-year recurrence rate, one-year mortality, and one-year disease-free survival rate. Results: Six studies were included for meta-analysis. In total, 234 patients were in the RRH group and 174 patients were in the LRH group. RRH had significantly longer operative time (MD=14.23,95% CI:5.27~23.20, P=0.002),shorter hospital stay (MD= -1.10,95% CI:-1.43~0.76, P <0.00001),more dissected pelvic lymph nodes(MD=0.89,95%CI:0.18~1.60, P =0.01) and less blood loss(WMD = -27.78,95%CI:-58.69 ~ -3.14, P=0.08, I2 = 80%) compared with LRH. No significant difference was observed between two groups regarding positive surgical margin (OR = 0.59, 95% CI 0.18~2.76, P=0.61), over complications (OR = 0.77, 95% CI, 0.46-1.28, P=0.31), one-year recurrence rate (OR = 0.19, 95% CI 0.03-1.15, P=0.13), one-year mortality rate (OR = 0.19, 95% CI 0.03-1.15, P=0.07) and disease-free survival at one year (OR = 1.92, 95% CI 0.32-11.50, P=0.48). Conclusion: RRH is an increasingly popular surgical method known for its high level of security and efficiency. It has many benefits in comparison to LRH, such as decreased blood loss, a higher quantity of dissected pelvic lymph nodes, and a shorter duration of hospitalization. Further multicenter, randomized controlled trials with extended follow-up durations are necessary to conclusively determine the safety and efficacy of RRH, as no significant differences were observed in terms of positive surgical margin, postoperative complications, 1-year recurrence, 1-year mortality, and 1-year disease-free survival. Systematic Review Registration: PROSPERO, identifier CRD42023446653.

A short-term of starvation improved the antioxidant activity and quality of African catfish (Clarias gariepinus).

Clarias gariepinus is an important freshwater fish with high economic value and breeding potential in China. It is a fast-growing and adaptable catfish, but the main problems facing the current market are its low price and poor taste, although starvation is a good solution to these problems. In this study, the effects of starvation on the physiology, biochemistry, and muscle quality of C. gariepinus were investigated. The results showed that compared with the control group, the weight gain rate and specific growth rate of the starvation group were significantly different. Body weight, visceral weight, condition factor, viscerosomatic index, hepatosomatic index, and viscera fat index all decreased, while visceral weight and hepatosomatic index decreased significantly after starvation for 30 days. The hardness and crude protein of muscle increased significantly and crude lipid decreased significantly. Taste-enhancing amino acids increased slightly, and fatty acids increased significantly. Compared with the control group, starvation led to changes in antioxidant defense parameters. The level of malondialdehyde (MDA) in liver increased significantly; the activities of superoxide dismutase (SOD) increased in serum after 30 days; the activities of glutathione peroxidase (GSH-Px) increased considerably in the serum and liver after 15 days; the activities of alanine aminotransferase (ALT) increased considerably in the serum and liver after 30 days. The in-depth study of changes in physiological, biochemical, and nutritional components of fish under starvation is helpful to understand the ecological strategy of fish to adapt to starvation and of great guiding significance for fishery resource management and aquaculture production.

Effects of flora deficiency on the structure and function of the large intestine.

The significant anatomical changes in large intestine of germ-free (GF) mice provide excellent material for understanding microbe-host crosstalk. We observed significant differences of GF mice in anatomical and physiological involving in enlarged cecum, thinned mucosal layer and enriched water in cecal content. Furthermore, integration analysis of multi-omics data revealed the associations between the structure of large intestinal mesenchymal cells and the thinning of the mucosal layer. Increased Aqp8 expression in GF mice may contribute to enhanced water secretion or altered hydrodynamics in the cecum. In addition, the proportion of epithelial cells, nutrient absorption capacity, immune function and the metabolome of cecum contents of large intestine were also significantly altered. Together, this is the first systematic study of the transcriptome and metabolome of the cecum and colon of GF mice, and these findings contribute to our understanding of the intricate interactions between microbes and the large intestine.

Comparison of percutaneous nephrolithotomy and flexible ureterorenoscopy in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters: a retrospective study.

PURPOSE: To compare the efficacy and safety of micropercutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS) in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters. METHODS: This study is a retrospective analysis that combines a review of medical records with an outcomes management database. A total of 163 patients who underwent MPCNL and 137 patients who had FURS were identified between January 2017 and December 2021. Demographic data, operation time, hospitalization time, stone-free rate, and complication rate were collected and analyzed. RESULTS: Preoperative general data of sex, age, BMI, serum creatinine, time of stone existence, stone hardness, stone diameter, preoperative hydronephrosis, and preoperative infection of the MPCNL group have no statistically significant difference with that of the FURS group. All MPCNL or FURS operations in both groups were successfully completed without any instances of reoperation or conversion to another surgical procedure. Patients who underwent MPCNL had a considerably reduced operation time (49.6 vs. 72.4 min; P<0.001), but a higher duration of hospitalization (9.1 vs. 3.9 days; P<0.001) compared to those who underwent FURS. The stone-free rate in the MPCNL group was superior to that of the FURS group, with a percentage of 90.8% compared to 71.5% (P<0.001). There was no statistically significant disparity in the rate of complications between the two groups (13.5% vs. 15.3%; P = 0.741). CONCLUSION: Both MPCNL and FURS are viable and secure surgical choices for individuals with solitary upper ureteral calculi measuring 1 to 2 cm. The FURS procedure resulted in a shorter duration of hospitalization compared to MPCNL. However, it had a comparatively lower rate of successfully removing the stones and required a longer duration for the operation.There were no substantial disparities observed in the complication rate between the two groups.FURS is the preferable option for treating uncomplicated upper ureteral calculi, whereas MPCNL is the preferable option for treating complicated upper ureteral calculi.Prior to making treatment options, it is crucial to take into account the expertise of surgeons, the quality of the equipment, and the preferences of the patient. TRIAL REGISTRATION: No.

Single-cell and spatiotemporal transcriptomic analyses reveal the effects of microorganisms on immunity and metabolism in the mouse liver.

The gut-liver axis is a complex bidirectional communication pathway between the intestine and the liver in which microorganisms and their metabolites flow from the intestine through the portal vein to the liver and influence liver function. In a sterile environment, the phenotype or function of the liver is altered, but few studies have investigated the specific cellular and molecular effects of microorganisms on the liver. To this end, we constructed single-cell and spatial transcriptomic (ST) profiles of germ-free (GF) and specific-pathogen-free (SPF) mouse livers. Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) revealed that the ratio of most immune cells was altered in the liver of GF mice; in particular, natural killer T (NKT) cells, IgA plasma cells (IgAs) and Kupffer cells (KCs) were significantly reduced in GF mice. Spatial enhanced resolution omics sequencing (Stereo-seq) confirmed that microorganisms mediated the accumulation of Kupffer cells in the periportal zone. Unexpectedly, IgA plasma cells were more numerous and concentrated in the periportal vein in liver sections from SPF mice but less numerous and scattered in GF mice. ST technology also enables the precise zonation of liver lobules into eight layers and three patterns based on the gene expression level in each layer, allowing us to further investigate the effects of microbes on gene zonation patterns and functions. Furthermore, untargeted metabolism experiments of the liver revealed that the propionic acid levels were significantly lower in GF mice, and this reduction may be related to the control of genes involved in bile acid and fatty acid metabolism. In conclusion, the combination of sc/snRNA-seq, Stereo-seq, and untargeted metabolomics revealed immune system defects as well as altered bile acid and lipid metabolic processes at the single-cell and spatial levels in the livers of GF mice. This study will be of great value for understanding host-microbiota interactions.

Comparison of robotic-assisted versus conventional laparoscopic surgery in colorectal cancer resection: a systemic review and meta-analysis of randomized controlled trials.

Introduction: There is still controversy on whether or not robot-assisted colorectal surgery (RACS) have advantages over laparoscopic-assisted colorectal surgery(LACS). Materials and methods: The four databases (PubMed, Embase, Web of Science and Cochrane Library)were comprehensively searched for randomized controlled trials (RCTs) comparing the outcomes of RACS and LACS in the treatment of colorectal cancer from inception to 22 July 2023. Results: Eleven RCTs were considered eligible for the meta-analysis. Compared with LACS,RACS has significantly longer operation time(MD=5.19,95%CI: 18.00,39.82, P<0.00001), but shorter hospital stay(MD=2.97,95%CI:-1.60,-0.33,P = 0.003),lower conversion rate(RR=3.62,95%CI:0.40,0.76,P = 0.0003), lower complication rate(RR=3.31,95%CI:0.64,0.89,P=0.0009),fewer blood loss(MD=2.71,95%CI:-33.24,-5.35,P = 0.007),lower reoperation rate(RR=2.12, 95%CI:0.33,0.96,P=0.03)and longer distal resection margin(MD=2.16, 95%CI:0.04,0.94, P = 0.03). There was no significantly difference in harvested lymph nodes, the time of first flatus, the time of first defecation,the time of first resume diet, proximal resection margin, readmission rates, mortalities and CRM+ rates between two group. Conclusions: Our study indicated that RACS is a feasible and safe technique that can achieve better surgical efficacy compared with LACS in terms of short-term outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447088.

Comparison of robot-assisted thoracic surgery versus video-assisted thoracic surgery in the treatment of lung cancer: a systematic review and meta-analysis of prospective studies.

Introduction: Previous studies have compared robot-assisted thoracic surgery(RATS) with video-assisted thoracic surgery (VATS) in the treatment of patients with lung cancer, but results were conflicting. The present meta-analysis aimed to compare the clinical outcomes of RATS with VATS in the treatment of patients with lung cancer. Materials and methods: Web of Science, PubMed, Cochrane Library and Embase were comprehensively searched for randomized controlled trials or prospective cohort studies comparing the clinical outcomes of RATS and VATS from inception to 22 July 2023. The Cochrane Risk of Bias tool was used to assess risk of bias. Meta-analyses of length of hospital stay, postoperative duration of drainage, postoperative complications, operative time, conversion, estimated blood loss, the number of dissected lymph nodes and stations, 30-day readmission and 30-day mortality were performed. Results: In total 5 studies were included in the meta-analysis. A total of 614 patients were included, of which 299 patients were treated by RATS and 315 patients treated by VATS. Blood loss was significantly less in RATS group than that in VATS (MD = -17.14, 95% CI -29.96 ~ -4.33, P = 0.009). More nodes stations were dissected in RATS group compared with VATS group(MD= 1.07, 95% CI 0.79 ~ 1.36, P < 0.001). No significant difference occurred between RATS and VATS in length of hospital stay(MD= -0.19, 95% CI -0.98~0.61), readmission(OR=0.74, 95%CI 0.36~1.51, P=0.41), operative time(MD=11.43 95% CI -8.41~31.26, P=0.26), conversion(OR=0.58, 95% CI 0.29~1.17, P=0.13), number of dissected lymph nodes(MD=0.98, 95% CI -0.02~1.97, P=0.05), upstaging rate(OR =0.67, 95% CI 0.38 ~ 1.18, P =0.16, I2 = 0%), time of chest tube drainage (MD= -0.34, 95%CI -0.84~0.15, P=0.17), post-operative complications(OR=0.76, 95% CI 0.52~ 1.11, P=0.16) and total cost(MD = 3103.48, 95% CI -575.78 ~ 6782.74, P=0.1, I2 = 99%). Conclusion: RATS is a feasible and safe treatment that can achieve better surgical outcomes compared with VATS in terms of short-term outcomes. Except of higher total cost, RATS has obvious advantage in lymphadenectomy and control of intraoperative bleeding. However, large sample and long follow-up randomized clinical trials comparing RATS with VATS are still necessary to better demonstrate the advantages of RATS for lung cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier CRD42023446653.

Total hip arthroplasty versus hemiarthroplasty in the treatment of active elderly patients over 75 years with displaced femoral neck fractures: a retrospective study.

BACKGROUND: Femoral neck fractures are associated with substantial morbidity and mortality for older adults. Total hip arthroplasty (THA) and hemiarthroplasty (HA) are widely used in elderly patients with displaced femoral neck fractures (DFNF), but there is still controversy refering to the optimal chose for the management of DFNF in active elderly patients. METHODS: This is a retrospective cohort study that incorporates medical record review with an outcomes management database. 73 patients who underwent HA and 66 patients who underwent THA were identified from January 2015 to December 2017. Data of age, gender, BMI, comorbidity status, operation time, blood loss, hospitalization time, in-hospital complication were collected and analyzed. Clinical follow-up and radiographic examinations were performed at approximately five years, and hip complications, Harris Hip Score (HHS) and EuroQol-5 Dimensions (EQ-5D) were assessed. RESULTS: Preoperative general data of sex, age, BMI and charlson comorbidity score of THA group(n=55) has no statistically significant difference with that of HA group. Patients treated by THA had significantly longer operation time (105.5 vs 76.7 minutes; P < 0.001), more blood loss (524.1 vs 350.1 ml; P < 0.001) and longer hospitalization time (15.8 vs 13.8 days; P < 0.001). There was no significant differences between two groups in complications (32.7% vs 25.8%, P=0.432). No patients died during the hospitalization. After five years, only 33 patients in the THA group and 34 patents in the HA group were still alive, and the fraction surviving were not statistically significant between two groups (60.0% vs 54.8%, P> 0.05). The differences in hip function in favor of THA appeared to increase after the five-year follow-up, and the difference was significant in terms of the total Harris hip score (81.3 vs 73.1, P < 0.001) as well as in the dimensions of pain (38.9 vs 35.9, P=0.033), function (33.7 vs 29.2, P=0.001), absence of deformity (4.0 vs 3.9, P=0.023) and range of motion (4.6 vs 4.2, P=0.008). There was no significant differences between groups in hip dislocation rate (6.1% vs 0.0%, P=0.239). The erosion rate of hip joint in the THA group was significantly lower than that of the HA group (0.0% vs 26.5%, P=0.002). The health-related quality of life, according to EQ-5D index score, was found to be higher (0.69 vs 0.63, P= 0.001) in the THA group than the HA group after five years. CONCLUSION: THA may be a preferred management option for active elderly patients over 75 years. The more extensive surgery of THA is not associated with higher in-hospital complication rate or mortality rate. These patients can benefit from THA in terms of hip function and quality of life. TRIAL REGISTRATION: No.

Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and Stereo-seq.

Gut microbes exhibit complex interactions with their hosts and shape an organism's immune system throughout its lifespan. As the largest secondary lymphoid organ, the spleen has a wide range of immunological functions. To explore the role of microbiota in regulating and shaping the spleen, we employ scRNA-seq and Stereo-seq technologies based on germ-free (GF) mice to detect differences in tissue size, anatomical structure, cell types, functions, and spatial molecular characteristics. We identify 18 cell types, 9 subtypes of T cells, and 7 subtypes of B cells. Gene differential expression analysis reveals that the absence of microorganisms results in alterations in erythropoiesis within the red pulp region and congenital immune deficiency in the white pulp region. Stereo-seq results demonstrate a clear hierarchy of immune cells in the spleen, including marginal zone (MZ) macrophages, MZ B cells, follicular B cells and T cells, distributed in a well-defined pattern from outside to inside. However, this hierarchical structure is disturbed in GF mice. Ccr7 and Cxcl13 chemokines are specifically expressed in the spatial locations of T cells and B cells, respectively. We speculate that the microbiota may mediate the structural composition or partitioning of spleen immune cells by modulating the expression levels of chemokines.

Reducing complications of femoral neck fracture management: a retrospective study on the application of multidisciplinary team.

BACKGROUND: Femoral neck fractures are associated with substantial morbidity and mortality for older adults. Multi-system medical diseases and complications can lead to long-term care needs, functional decline and death, so patients sustaining hip fractures usually have comorbid conditions that may benefit from application of multidisciplinary team(MDT). METHODS: This is a retrospective cohort study that incorporates medical record review with an outcomes management database. 199 patients were included who had surgery for a new unilateral femoral neck fracture from January 2018 to December 2021 (96 patients in usual care (UC) model and 103 patients in MDT model. High-energy, pathological, old and periprosthetic femoral neck fracture were excluded. Age, gender, comorbidity status, time to surgery, and postoperative complication, length of stay, in-hospital mortality, 30-day readmission rate, 90-day mortality data were collected and analyzed. RESULTS: Preoperative general data of sex, age, community dwelling and charlson comorbidity score of MDT group (n = 103) have no statistically significant difference with that of usual care (UC) group. Patients treated in the MDT model had significantly shorter times to surgery (38.5 vs. 73.4 h;P = 0.028) and lower lengths of stay (11.5 vs. 15.2 days;P = 0.031). There were no significant differences between two models in In-hospital mortality (1.0% vs. 2.1%; P = 0.273), 30-day readmission rate (7.8% vs. 11.5%; P = 0.352) and 90-day mortality (2.9% vs. 3.1%; P = 0.782). The MDT model had fewer complications overall (16.5% vs. 31.3%; P = 0.039), with significantly lower risks of delirium, postoperative infection, bleeding, cardiac complication, hypoxia, and thromboembolism. CONCLUSION: Application of MDT can provide standardized protocols and a total quality management approach, leading to fewer complications for elderly patients with femoral neck fracture. TRIAL REGISTRATION: No.

Efficacy and safety of anti-interleukin-1 therapeutics in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to evaluate the efficacy and safety of anti-interleukin-1 therapeutics, including IL-1 antibodies, interleukin-1 receptor antagonists (IL-1 Ras) and IL-1 inhibitors, for knee osteoarthritis (KOA) treatment. METHODS: Databases (Medline, Embase, Web of Science and CENTRAL) and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) of anti-interleukin-1 therapeutics from inception to August 31, 2022. The outcomes were the mean change in pain and function scores and the risk of adverse effects (AEs). RESULTS: In the 12 studies included, anti-interleukin-1 therapeutics were superior to placebo in terms of pain relief (standardized mean difference [SMD] = - 0.38, 95% confidence interval [CI] = - 1.82 to - 0.40, p < 0.001, I2 = 77%) and functional improvement (SMD = - 1.11, 95% CI = - 1.82 to - 0.40, p = 0.002, I2 = 96%). The incidence of any AE (risk ratio [RR] = 1.02, 95% CI = 0.88-1.18, p < 0.001, I2 = 76%) was higher following treatment with anti-interleukin-1 therapeutics than placebo, while no significant difference was found in the incidence of serious AEs (SAEs) or discontinuations due to AEs. Subgroup analyses showed that IL-1 antibodies and the IL-1 inhibitor provided pain relief (IL-1 antibodies: SMD = - 0.61, 95% CI = - 0.92 to - 0.31, p < 0.001; IL-1 inhibitor: SMD = - 0.39, 95% CI = - 0.72 to - 0.06, p = 0.02, I2 = 74.0%) and functional improvement (IL-1 antibodies: SMD = - 1.75, 95% CI = - 2.10 to - 1.40, p < 0.001; IL-1 inhibitor: SMD = - 0.28, 95% CI = - 0.83 to 0.27, p = 0.31, I2 = 88%) superior to those of placebo, whereas IL-1 Ras did not. However, the IL-1 inhibitor increased the incidence of any AE (RR = 1.35, 95% CI = 0.92-1.98, p < 0.001, I2 = 85%) but not the risk of SAEs or discontinuations due to AEs. IL-1 antibodies and IL-1 Ras showed no difference in safety compared with placebo. CONCLUSIONS: Anti-interleukin-1 therapeutics could relieve OA-related pain and improve function, but is probably associated with an increased risk of adverse events. Specially, IL-1 antibodies and an IL-1 inhibitor could relieve OA-related pain and improve function, whereas IL-1 Ras could not. IL-1 antibodies and IL-1 Ras were relatively safe options, but IL-1 inhibitors were associated with safety concerns.

Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors for muscle invasive bladder cancer: a systematic review and meta-analysis.

Introduction: This meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscle-invasive bladder carcinoma (MIBC). Materials and methods: Four databases (Medline, Embase, Web of Science, and 21 CENTRAL) were searched for articles studying neoadjuvant PD-(L)1 inhibitors for MIBC. The search time period was from the establishment of each database to 21 July 2023. Meta-analyses of pCR, pPR, Grade≥ 3 irAEs rate, RFS, and OS were performed. Results: In total, 22 studies were included for meta-analysis. The overall pooled pCR of neoadjuvant PD-(L)1 inhibitors was 0.36 (95%CI=0.30-0.42, p=0.00). In subgroup meta-analysis, the pooled PCR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.27 (95%CI=0.19-0.35, p=0.1), 0.41 (95%CI=0.21-0.62, p=0.01), 0.43 (95%CI=0.35-0.50, p=0.06), respectively. The overall pooled pPR of neoadjuvant PD-(L)1 inhibitors was 0.53 (95%CI=0.46-0.60, p=0.00). In subgroup meta-analysis, the pooled pPR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.36 (95%CI=0.22-0.51, p=0.01), 0.51 (95%CI=0.39-0.62, p=0.43), and 0.61 (95%CI=0.53-0.69, p=0.01), respectively. Kaplan-Meier curves for OS and RFS were reconstructed, but there was no significant difference among three groups in terms of OS or RFS. The pooled result of Grade≥ 3 irAEs rate for neoadjuvant PD-(L)1 inhibitors was 0.15 (95%CI=0.09-0.22, p=0.00%). In subgroup analysis, the pooled result of Grade≥ 3 irAEs rate for PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.07 (95%CI=0.04-0.11, p=0.84), 0.31 (95%CI=0.16-0.47, p=0.06), and 0.17 (95%CI=0.06-0.31, I2 = 71.27%, p=0.01), respectively. Conclusion: Neoadjuvant PD-(L)1 inhibitors were feasible and safe for muscle invasive bladder cancer. Compared with PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI and PD-(L)1 inhibitors plus chemotherapy were associated with higher pCR and pPR, but higher Grade≥3 irAEs. Kaplan-Meier curves for OS and RFS indicated that neoadjuvant PD-(L)1 inhibitors had an acceptable long-term prognostic, but it was not possible to discern statistical differences between the three neoadjuvant subgroups. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452437, identifier PROSPERO (CRD42023452437).

Assessment of patient experiences following total sacrectomy for primary malignant sacral tumors: A qualitative study.

BACKGROUND AND OBJECTIVES: Few reports have investigated patient experiences following total en bloc sacrectomy. The aims of this study were to obtain a deeper understanding of patients' personal experiences, needs, and satisfaction with the treatment to reveal areas in which perioperative and long-term patient care can be improved. METHODS: A qualitative design was applied to examine patient experiences and supportive care needs. Patients treated between 2007 and 2017 were identified from our institutional database. RESULTS: A total of 28 survivors were interviewed (13 females, age 13-75 years). Eight themes were identified: the effect of surgery on patients' (a) daily lives, (b) social activities, (c) work or school activities, (d) and family lives; (e) acceptance of ostomy surgery; (f) need for guidance regarding long-term rehabilitation; (g) satisfaction with the medical services provided in the hospital; and (h) satisfaction with the treatment outcomes. CONCLUSION: Total en bloc sacrectomy can yield satisfactory oncological outcomes; however, the procedure is a life-changing event for patients and their families. Physicians must provide long-term support and guidance after surgery to enable patients to fully understand and cope with the changes in their lives.

Construction of a recombinant eukaryotic expression vector containing DNM3 gene and its expression in colon cancer cells.

INTRODUCTION: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited. MATERIALS AND METHODS: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot. RESULT: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P<0.001). DNM3 downregulated the protein expression of MMP-2 and MMP-9. CONCLUSION: DNM3 may weaken the malignant behavior of colon cancer and may have promoted the invasion and migration of colon cancer by regulating the expression of MMP-2 and MMP-9.

Correlation of fractalkine concentrations in serum and synovial fluid with the radiographic severity of knee osteoarthritis.

BACKGROUND: Fractalkine has been detected in synovial fluid (SF) from osteoarthritis (OA) patients. This study aims to examine the relation of fractalkine concentrations in serum and SF with the radiographic severity of OA. METHODS: Fractalkine concentrations of serum and SF were measured using an enzyme-linked immunosorbent assay method in 223 patients with knee OA and 165 healthy controls. The progression of OA was classified according to the Kellgren-Lawrence grading system. RESULTS: Elevated concentrations of fractalkine in serum were found in knee OA patients compared with healthy controls [all results median (interquartile range) 226.25 (183.19-259.91) vs. 127.42 (99.54-154.98) pg/mL, P < 0.001]. The case group included 71 knee OA patients with grade 2, 98 with grade 3, and 54 with grade 4. Knee OA patients with KL grade 4 had significantly higher fractalkine concentrations in serum and SF compared with those with KL grade 2 and 3 [serum: 247.68 (215.05-278.64) vs. 212.45 (169.19-247.96) pg/mL, P < 0.001, and 247.68 (215.05-278.64) vs. 222.00 (179.80-254.98) pg/mL, P = 0.005, respectively; SF: 94.95 (76.46-106.68) vs. 74.31 (63.64-84.79) pg/mL, P < 0.001, and 94.95 (76.46-106.68) vs. 80.34 (68.84-96.39) pg/mL, P = 0.001, respectively]. Knee OA patients with KL grade 3 showed significantly elevated concentrations of fractalkine in SF compared with those with KL grade 2 [80.34 (68.84-96.39) vs. 74.31 (63.64-84.79) pg/mL, P = 0.004]. Fractalkine concentrations in serum and SF of knee OA patients were both significantly associated with the disease severity evaluated by KL grading criteria (r = 0.261, P < 0.001 and r = 0.366, P < 0.001, respectively). CONCLUSION: The fractalkine concentrations in serum and SF may serve as an effective biomarker for the severity of OA.