BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.