Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

Objective:To develop a camelid single-domain antibody (SdAb) recognizing linear B-cell epitopes in glutamate dehydrogenase of Clostridium difficile(CD-GDH), and to apply it in Western blot and ELISA. Methods:Purified recombinant CD-GDH was used as bait to screen phage-displayed camelid SdAb library and obtain positive clones. Then those clones were confirmed by Western blot, and their variable domain of heavy chain of heavy chain antibody(VHH) nucleotide sequence were determined. The VHH sequence was synthesized after codon optimization and cloned into the expression vector pET28a. The SdAb was then expressed and purified, and its ability to detect CD-GDH protein in multiple assays was further explored.Results:Six positive clones were obtained, among which clone GA4 was chosen for recombinant expression in Escherichia coli and further purification. The purified GA4 binded well with CD-GDH with a Kd value of 3 nmol/L. In Western blot and ELISA, GA4 was proven to be able to selectively detect both recombinant and endogenous CD-GDH. Conclusions:A camelid SdAb targeting a linear B-cell epitope in CD-GDH is successfully developed, which provides a very useful tool for detecting CD-GDH.

Objective To observe the value of subchondral bone(SB)intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)for quantitatively evaluating knee joint cartilage degeneration.Methods Totally 125 patients with knee cartilage degeneration were prospectively enrolled and divided into mild group(n=65,Outerbridge grades Ⅰ-Ⅱ)and moderate-severe group(n=60,Outerbridge grades Ⅲ-Ⅳ)based on arthroscopic findings.Additionally,30 healthy young subjects were recruited as control group.The apparent diffusion coefficient(ADC),true diffusion coefficient(D),pseudo diffusion coefficient(D*)and perfusion fraction(f)values of medial condyle of SB of femur,lateral condyle of femur,medial tibial plateau and lateral tibial plateau,as well as the mean values of each parameter of the above 4 regions were obtained based on knee joint IVIM-DWI and compared within and among groups.Spearman correlation analysis was used to observe the correlations between quantitative parameters and Outerbridge grading.The area under the receiver operating characteristic curve(AUC)was calculated to evaluate the efficacy of each quantitative parameter alone and their combination for assessing knee cartilage degeneration.Results Significant differences of D*values were found among different parts of knee joint SB in moderate-severe group,also of D value,D* value and f value among different parts of knee joint SB in mild group(all P＜0.05).Significant differences of IVIM-DWI parameter were found among different parts of knee joint SB in control group(all P＜0.05).ADC value of knee joint SB in moderate-severe group,mild group and control group decreased successively,while D value increased successively(all P＜0.001).D* values of knee joint SB in moderate-severe group was higher than that in mild group and control group(both P＜0.05).No significant difference of f value of knee joint SB was found between moderate-severe group and mild group(P＞0.05),while both the latter two were higher than that in control group(both P＜0.05).ADC value,D value and f value of knee joint SB were positively correlated(rs=0.671,0.634,0.416,all P＜0.01),while D* value of knee joint SB was negatively correlated with Outerbridge grading(rs=-0.729,P＜0.01).AUC of combination of parameters for distinguishing mild group from control group,and mild group from moderate-severe group was 0.859 and 0.808,respectively.Conclusion SB IVIM-DWI could be used for quantitatively evaluation of knee cartilage degeneration.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Objective To investigate the influence of basic condition,surgical strategy,and postoperative condition of adolescent idiopathic scoliosis(AIS)patients on the length of hospitalization.Methods A total of 145 AIS patients who underwent posterior spinal fusion and internal fixation in The First Affiliated Hospital of Naval Medical University(Second Military Medical University)from Jan.1,2014 to Dec.31,2023 with more than 2 years of follow-up were retrospectively enrolled.According to the surgical strategy,they were assigned to selective fusion group(n=50)and non-selective fusion group(n=95).AIS patients were assigned to intensive care unit(ICU)group(n=81)and non-ICU group(n=64)according to whether they were admitted to ICU.Parameters related to basic,surgical and postoperative conditions,hospital stay and postoperative hospital stay were analyzed.Multiple linear regression analysis was used to study the influencing factors of hospital stay and postoperative hospital stay.Results The number of surgical segments,surgical time,intraoperative blood loss,drainage volume on the 3rd day postoperatively,hospital stay,and postoperative hospital stay in the selective fusion group were significantly less than those in the non-selective fusion group(all P＜0.05).The patients in the ICU group were younger,had longer surgery time,had more intraoperative blood loss and blood transfusion,and had longer hospital stay and postoperative hospital stay compared with those in the non-ICU group(all P＜0.05).Correlation analysis showed that hospital stay and postoperative hospital stay were both positively correlated with ICU admission(r=0.179,0.240;both P＜0.05)and were both negatively correlated with selective fusion(r=-0.187,-0.242;both P＜0.05).Conclusion The hospital stay and postoperative hospital stay of AIS patients with non-selective fusion in posterior spinal fusion and internal fixation is longer than those of patients with selective fusion.Non-selective fusion and ICU admission may be factors contributing to the prolonged hospital stay and postoperative hospital stay in AIS patients.

Objective To analyze the willingness and influencing factors of doctors in Beijing public hospitals to set up clinics in the community,and to provide scientific basis for promoting quality health technicians to go down to the grassroots and realize hierarchical diagnosis and treatment.Methods Doctors from 6 specialized hospita ls and 3 general hospitals in Beijing were selected as subjects for questionnaire survey.By stratified sampling,a questionnaire survey was conducted on 518 doctors from 9 public hospitals in Beijing through stratified sampling method.Descriptive analysis,rank sum test and ordered logistic regression were used to explore doctors'willingness to open clinics and its influencing factors.Results In all survey respondents,212(40.93%)physicians were very or somewhat willing to open a clinic in the community,physicians with higher benefit perception,and greater willingness to publicize relevant policies were more willing to set up clinics.Conclusion Opening of clinics by doctors in public hospitals is affected by perceived benefits and willingness to advocate policies.It is suggested to further improve relevant systems and policies,reduce the risk of doctors opening clinics,and promote doctors in public hospitals to open clinics in communities,so as to realize the sinking of high-quality health human resources to the grassroots.

Objective To explore the impact of organizational innovation climate in public hospitals on doctors'innovation performance,providing a reference for improving doctors'innovation performance.Methods A questionnaire survey was conducted with practicing(assistant)physicians in 22 hospitals in Beijing,and 1 859 questionnaires were effectively recovered.The scores of hospital organizational innovation climate,physicians'individual innovation performance,innovation behavior,and innovation self-efficacy were analyzed by Pearson correlation;the partial least squares structural equation modeling was further used to explore the role of the organizational innovation climate of hospitals on physicians'innovation performance.Results The path of hospital organizational innovation climate on physicians'innovation performance.The difference in path coefficients for the mediating effect of hospital organizational innovation climate significantly affecting physicians'innovation performance,and physicians'innovation self-efficacy between hospital innovation climate and physicians'innovation behavior and innovation performance was statistically significant(P＜0.001).Conclusion The innovation performance of practicing(assistant)physicians in Beijing municipal hospitals is influenced by the organizational innovation climate,physicians'innovation self-efficacy and innovation behaviors,and physicians'innovation self-efficacy and innovation behaviors play a chain-mediated role.It is suggested that public hospitals should strengthen doctors'self-efficacy and consider the fit between the construction of innovation atmosphere and actual needs to stimulate innovation behavior and ultimately improve inno-vation performance.

Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.