Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

To further standardize the management of vaccination units, the Specifications for Vaccination (2023 version) proposes hierarchical management. However, guidelines for establishing, implementing, and evaluating such a framework remain underdeveloped. This paper systematically reviews the current status of hierarchical management in vaccination units, clarifies its feasibility and necessity, and proposes an implementation scheme.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective To investigate the application value of systemic inflammatory response index(SIRI)in patients with acute-on-chronic liver failure(ACLF)and co-infection.Methods A retrospective analysis was performed for the clinical data of 579 ACLF patients with co-infection who were diagnosed and treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to March 2016,including demographic features,laboratory markers,and complications,and SIRI,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and Child-Pugh score were calculated.According to the results of follow-up on day 90,the patients were divided into survival group with 210 patients and death group with 369 patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test were used for comparison of categorical data between two groups.The binary logistic regression analysis was used to investigate the independent risk factors for 90-day death.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to assess the performance of SIRI,MELD-Na score,and Child-Pugh score in predicting the prognosis of ACLF patients with co-infection.The Kaplan-Meier survival analysis was performed based on the optimal cut-off value of SIRI.Results Among the 597 ACLF patients with co-infection,384(66.32%)had HBV-related ACLF and 114(19.69%)had alcohol-related ACLF;as for the main infection sites,316(54.58%)had abdominal infection and 133(22.97%)had pulmonary infection;the 90-day mortality rate was 63.73%.The multivariate logistic regression analysis showed that SIRI(odds ratio[OR]=1.177,95%confidence interval[CI]:1.117-1.239,P<0.05),blood ammonia(OR=1.009,95%CI:1.001-1.018,P<0.05),MELD-Na score(OR=1.047,95%CI:1.016-1.080,P<0.05),Child-Pugh score(OR=1.351,95%CI:1.054-1.730,P<0.05),age(OR=1.045,95%CI:1.021-1.070,P<0.05),comorbidity with hepatic encephalopathy(OR=2.269,95%CI:1.305-3.946,P<0.05),and comorbidity with acute kidney injury(OR=1.730,95%CI:0.990-3.023,P<0.05)were independent risk factors for 90-day death in ACLF patients with co-infection.The Pearson correlation analysis showed that SIRI was positively correlated with MELD-Na score(r=0.282,P<0.001)and Child-Pugh score(r=0.168,P<0.001).SIRI,MELD-Na score,and Child-Pugh score had an AUC of 0.855,0.734,and 0.690,respectively,in predicting 90-day death,and SIRI had a higher predictive efficiency than MELD-Na score and Child-Pugh score(Z=4.922 and 6.289,both P<0.001),with a sensitivity of 76.7%and a specificity of 82.9%.In addition,SIRI combined with MELD-Na score or Child-Pugh score improved the predictive efficiency of MELD-Na score(0.854 vs 0.734,Z=6.899,P<0.001)and Child-Pugh score(0.858 vs 0.690,Z=8.725,P<0.001).The patients with high SIRI(≥4.08)had a 90-day survival rate of 11.29%(36/319),which was significantly lower than that in the patients with low SIRI(<4.08)(χ2=225.24,P<0.001).Conclusion SIRI is an independent risk factor for death in ACLF patients with co-infection and has a good clinical value in predicting prognosis,with the advantages of convenience and low costs.

To further standardize the management of vaccination units, the Specifications for Vaccination (2023 version) proposes hierarchical management. However, guidelines for establishing, implementing, and evaluating such a framework remain underdeveloped. This paper systematically reviews the current status of hierarchical management in vaccination units, clarifies its feasibility and necessity, and proposes an implementation scheme.

Objective To investigate the application value of systemic inflammatory response index(SIRI)in patients with acute-on-chronic liver failure(ACLF)and co-infection.Methods A retrospective analysis was performed for the clinical data of 579 ACLF patients with co-infection who were diagnosed and treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to March 2016,including demographic features,laboratory markers,and complications,and SIRI,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and Child-Pugh score were calculated.According to the results of follow-up on day 90,the patients were divided into survival group with 210 patients and death group with 369 patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test were used for comparison of categorical data between two groups.The binary logistic regression analysis was used to investigate the independent risk factors for 90-day death.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to assess the performance of SIRI,MELD-Na score,and Child-Pugh score in predicting the prognosis of ACLF patients with co-infection.The Kaplan-Meier survival analysis was performed based on the optimal cut-off value of SIRI.Results Among the 597 ACLF patients with co-infection,384(66.32%)had HBV-related ACLF and 114(19.69%)had alcohol-related ACLF;as for the main infection sites,316(54.58%)had abdominal infection and 133(22.97%)had pulmonary infection;the 90-day mortality rate was 63.73%.The multivariate logistic regression analysis showed that SIRI(odds ratio[OR]=1.177,95%confidence interval[CI]:1.117-1.239,P<0.05),blood ammonia(OR=1.009,95%CI:1.001-1.018,P<0.05),MELD-Na score(OR=1.047,95%CI:1.016-1.080,P<0.05),Child-Pugh score(OR=1.351,95%CI:1.054-1.730,P<0.05),age(OR=1.045,95%CI:1.021-1.070,P<0.05),comorbidity with hepatic encephalopathy(OR=2.269,95%CI:1.305-3.946,P<0.05),and comorbidity with acute kidney injury(OR=1.730,95%CI:0.990-3.023,P<0.05)were independent risk factors for 90-day death in ACLF patients with co-infection.The Pearson correlation analysis showed that SIRI was positively correlated with MELD-Na score(r=0.282,P<0.001)and Child-Pugh score(r=0.168,P<0.001).SIRI,MELD-Na score,and Child-Pugh score had an AUC of 0.855,0.734,and 0.690,respectively,in predicting 90-day death,and SIRI had a higher predictive efficiency than MELD-Na score and Child-Pugh score(Z=4.922 and 6.289,both P<0.001),with a sensitivity of 76.7%and a specificity of 82.9%.In addition,SIRI combined with MELD-Na score or Child-Pugh score improved the predictive efficiency of MELD-Na score(0.854 vs 0.734,Z=6.899,P<0.001)and Child-Pugh score(0.858 vs 0.690,Z=8.725,P<0.001).The patients with high SIRI(≥4.08)had a 90-day survival rate of 11.29%(36/319),which was significantly lower than that in the patients with low SIRI(<4.08)(χ2=225.24,P<0.001).Conclusion SIRI is an independent risk factor for death in ACLF patients with co-infection and has a good clinical value in predicting prognosis,with the advantages of convenience and low costs.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.