OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

This paper reports a 45-year-old female patient with lung squamous cell carcinoma who received chemotherapy for multiple systemic metastases,and then 171 mg of the immune checkpoint inhibitor serplulimab was added,ivd,d1(21 d as a cycle).After 2 cycles of treatment,the patient developed dizziness and nausea,and tumor brain metastasis was considered.The lung CT showed that the irregular mass shadow in the anterior segment of the upper lobe of the right lung was enlarged compared with the previous one,and MRI of the liver showed patchy abnormal signal in the liver segment Ⅳ.PET-CT showed that the lung,liver,adrenal gland,left groin and multiple bones were all progressed compared with the previous progress.It was considered to be tumor hyperprogression caused by serplulimab.Serplulimab was immediately discontinued and methylprednisolone was given for symptomatic treatment,but the patient still died due to overprogression.The Naranjo's Assessment Scale was used to evaluate the correlation between the tumor progression and serplulimab in this case,and the result was' likely to be related'.This case suggested that,the prognosis of tumor hyperprogression caused by immune checkpoint inhibitors has a poor prognosis,the clinical use of immune checkpoint inhibitors should be alert to this situation,and pay attention to early differential diagnosis and timely treatment to avoid serious consequences.

Objective To evaluate the clinical efficacy of Shexiang Tongxin dropping pills combined with"Quadruple therapy"in elderly patients with heart failure with preserved ejection fraction(HFpEF).Methods A total of 193 elderly HFpEF patients admitted to Affiliated Hospital of Yangzhou University from January to June 2022 were selected as study objects,and were divided into observation group(97 cases)and control group(96 cases)according to random number table method.The control group was treated with sacubitril valsartan sodium tablets+dapagliflozin tablets+metoprolol tartrate tablets+spironolactone tablets,and the observation group was treated with Shexiang Tongxin dropping pills on the basis of control group treatment,and both groups were treated for 6 months.The changes of cardiac function indexes,serum myocardial injury markers,endothelial function and inflammation indexes before and after treatment were compared between two groups.The average length of hospitalization,readmission rate within 30 days and the effective rate of treatment were analyzed.After 6 months of follow-up,the 6-minute walk test,6-month readmission rate and the incidence of major adverse cardiovascular event(MACE)were compared between two groups.Results After 30 days of treatment,the total effective rate of observation group was significantly higher than that of control group(93.8％vs.90.6％,x2=3.982,P=0.031).After 30 days of treatment,left ventricular end diastolic diameter,left ventricular end systolic diameter,N-terminal pro-brain natriuretic peptide,cardiac troponin I,nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 in observation group were significantly lower than those in control group,left ventricular ejection fraction,early peak mitral valve diastolic blood flow velocity(E)/advanced peak mitral valve diastolic blood flow velocity(A)and nitric oxide were significantly higher than those in control group,and 6 min walking distance was significantly longer than that in control group(P＜0.05).After 6 months of follow-up,the average length of hospital stay in observation group was significantly lower than that in control group,and the readmission rate within 30 days was significantly lower than that in control group(P＜0.05).There was no significant difference in the 6-month readmission rate and the incidence of MACE between two groups(P＞0.05).Conclusion Shexiang Tongxin dropping pills can inhibit cardiac inflammation.Combined with the"Quadruple therapy",the clinical effect of HFpEF in elderly patients is better than that of western medicine alone,and it is worthy of clinical promotion and application.

[Objective]To explore Professor XU Guangxing's experience in differentiating and treating gastric cancer based on the"Yangming Weihe(stomach closed)"theory.[Methods]Through clinical shadowing,organizing and analyzing medical cases,and studying relevant literature,combined with Professor XU Guangxing's understanding of gastric cancer,this paper summarizes his experience in differentiating and treating gastric cancer based on the"Yangming Weihe"theory from the perspectives of theoretical connotation,etiology,pathogenesis and medication strategies.A medical case is included for validation.[Results]The theory of"Yangming Weihe"originates from the opening-closing-pivot theory.The Yangming closing mechanism serves as a component of the ascending and descending movement of Qi in the human body.Together with the Taiyin opening mechanism and the Jueyin closing mechanism,it collectively regulates the physiological functions of the stomach.Professor XU Guangxing proposes that the etiology and pathogenesis of gastric cancer can be categorized into three patterns:dysfunction of the Yangming closing mechanism;impaired Taiyin-Yangming opening-closing coordination;dual dysfunction of the Jueyin-Yangming closing mechanisms.His therapeutic strategies focus on:clearing heat,moistening dryness and promoting descending with bitter flavors to unblock Yangming;strengthening the spleen and harmonizing the middle-Jiao to support the opening-closing mechanism;dispersing wind pathogens and consolidating dissipation to restore the dual closing mechanisms.The attached medical case involved a postoperative gastric cancer patient,diagnosed as dual Jueyin-Yangming closing mechanism failure according to the"Yangming Weihe"theory.The treatment protocol emphasized:clearing dryness,nourishing Yin and unblocking-tonifying Yangming;dispersing wind,astringing dissipation and consolidating-descending Jueyin.The herbal regimen achieved stable and positive outcomes.[Conclusion]Professor XU Guangxing's approach to treating gastric cancer based on the"Yangming weihe"theory is characterized by unique insights into the etiology and pathogenesis,distinctive features in syndrome differentiation and treatment,and notable clinical efficacy.This methodology merits further research and broader promotion.

[Objective]To explore the academic characteristics of SHI Fa's On Continuation of Simple Formulas,the backbone physician of Yongjia medical school,and enrich the research on the academic thought of Yongjia medical school.[Methods]By using the method of literature research,through the study of On Continuation of Simple Formulas and other works of Yongjia medical school,combined with modern related research literature,this paper analyzes and sorts out the background,compilation principles and academic characteristics of On Continuation of Simple Formulas,and verifies it with medical cases.[Results]SHI Fa inherited the academic thoughts of CHEN Yan,the founder of Yongjia medical school,and his great disciple WANG Shuo,and corrected the oversimplification of Simple Formulas,"There is no difference between deficiency,excess,cold and heat syndromes,and one party governs one disease".Starting from clinical application,he not only pursued simplicity,but also pursued practicality.He abided by the principle of syndrome differentiation and treatment,adhered to the principle of pulse first and combination of pulse and disease,emphasized the protection of stomach Qi and the treatment of three causes,and advocated familiarity with medicinal properties and medication according to syndrome.The attached medical cases fully verified the fallacy of WANG Shuo's"one party governs all the syndromes"and the correctness of the academic characteristics of syndrome differentiation and treatment and addition and subtraction with the syndrome.[Conclusion]On Continuation of Simple Formulas attaches importance to the academic characteristics of syndrome differentiation,combination of pulse and disease,careful medication and protection of stomach Qi,which enriches the academic thought of Yongjia medical school and promotes the inheritance and development of Yongjia medical school.It also has enlightening significance for today's clinical diagnosis and treatment.

Objective:This study aims to explore the clinical characteristics of patients with multiple myeloma concurrently presenting with a second primary malignancy.By analyzing the causes based on literature reports,this study aims to deepen the understanding of multiple primary cancers in multiple myeloma patients,and provide some assistance for auxiliary examinations and risk assessments of multiple myeloma patients.Methods:A retrospective analysis was conducted on the clinical data of four patients with multiple myeloma who also had a second primary malignancy admitted to The Second Affiliated Hospital,Chongqing Medical University.Each patient was diagnosed with multiple myeloma through bone marrow aspiration and had a second primary malignancy confirmed through pathological biopsy.Results:The onset age of the 4 patients ranged from 42 to 81 years old;three were males and one was female.One patient had smoldering myeloma with a second primary hematological malignancy(follicular lymphoma),while the other 3 patients had concurrent solid malignancies,including bladder cancer,esophageal cancer,and breast cancer,respectively.Conclusion:Multiple myeloma accompanied by a second primary malignancy is rare,and early pathological biopsy is necessary for diagnosis to avoid missed diagnosis.

Oral potential malignant disorders (OPMDs) are a group of oral mucosal lesions with a risk of cancer transformation. The microenvironment surrounding the epithelial tissue is closely related to the malignant transformation of OPMDs. However, the changes and role of the periepithelial microenvironment during the malignant progression of OPMDs are not yet fully understood. This review discuss the impact of changes in the periepithelial microenvironment on the malignant transformation of OPMDs from following aspects: the immune microenvironment, stromal microenvironment, metabolic microenvironment, and oral microorganism. In the immune microenvironment, the immune surveillance capacity of periepithelial immune cells weakens, and some of these cells interact with malignant cells, resulting in an immunosuppressive microenvironment. Cells in the matrix promote the malignant transformation of OPMDs through the secretion of cytokines and nutritional support, along with extracellular matrix degradation and local angiogenesis. Epithelial cells undergo metabolic reprogramming during malignant transformation, while the resulting hypoxic microenvironment can further promote the malignant transition of epithelial cells. Oral microorganism fosters the malignant transformation of OPMDs by inducing inflammatory responses and creating hypoxic conditions.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.