The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.

Objective To evaluate the value of intrathecal synthetic related markers in patients with mild cognitive impairment(MCI),Alzheimer's disease(AD),and other types of dementia.Methods Retrospec-tively collect the clinical data of 577 patients diagnosed with MCI(MCI group,178 cases),AD(AD group,131 cases),and other types of dementia(other types group,268 cases)from June 2019 to July 2023 in Beijing Tiantan Hospital,Capital Medical University.Oligoclonal zone electrophoresis(OCB)and 24 h intrathecal pro-tein synthesis rate(ISR)of each group were investigated,and the difference of different indexes among the groups was compared to evaluate the value of related indexes in the differential diagnosis of different diseases.Results Compared with AD group and other groups,AD group had a higher proportion of females,more patients were＞50-70 years old,and the incidence of abnormal lipid metabolism was higher,with statistical significance(P＜0.05).There were significant differences in OB(S),cerebrospinal fluid albumin,serum albumin and cerebrospinal flu-id IgG in different disease groups(P＜0.05).IgG index and ISR in patients with positive SOB(CSF)were higher than those in negative and weakly positive patients,and the differences were statistically significant(P＜0.001).IgG index was positively correlated with ISR(r=0.878,P＜0.001).Conclusion Intrathecal synthetic mark-ers such as IgG index,SOB(CSF)and 24 h ISR have synergistic effects in the diagnosis of cognitive dysfunction and various dementias,which can be collectively utilized in the diagnosis of diseases.

Objective To explore the application value and related factors of serum carbonic anhydraseⅢ(CAⅢ)in the clinical diagnosis of mild to moderate Alzheimer disease(AD).Methods A total of 106 elderly patients initially diagnosed with mild to moderate AD at Huashan Hospital,Fudan University from October 2020 to November 2022 were enrolled as the AD group,and 89 healthy elderly people during the same period were enrolled as the control group.The serum biochemical indicators including liver and kidney function,blood lipids,blood glucose,folic acid and homocysteine were detected in both groups.Cognitive function was assessed by Mini-mental State Examination(MMSE).Patient Health Questionnaire-9(PHQ-9)and Generalized Anxiety Disorder-7(GAD-7)were used to assess psychological status.The activities of daily living(ADL)were assessed by modified Barthel Index(BI).Serum CAⅢlevels were measured by enzyme-linked immunosorbent assay(ELISA).Correlation analysis and multivariate linear regression analysis were used to identify factors influencing serum CAⅢlevels,and receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of serum CAⅢlevels in elderly patients with mild to moderate AD.Results The MMSE score of the AD group was significantly lower than that of the control group(P＜0.001),and the PHQ-9 and GAD-7 scores were significantly higher than those of the control group(P＜0.001).The serum CAⅢlevel in the AD group was significantly lower than that in the control group(P＜0.000 1).In patients with AD,serum CAⅢlevels in patients with a disease course＞3 years,accompanied by depression or anxiety,moderate AD,and serum creatinine≤111 μmol/L were significantly lower than those in patients with a disease course≤3 years,normal emotions,mild AD,and serum creatinine＞111 μmol/L(P＜0.05).Correlation analysis and multivariate linear regression analysis showed that serum CAⅢlevels were negatively correlated with disease duration,PHQ-9 score,GAD-7 scores and severity degree,positively correlated with serum creatinine level(P＜0.05).The PHQ-9 score,severity degree,and serum creatinine level were independent related factors for serum CAⅢlevel in mild to moderate AD elderly patients(P＜0.05).ROC curve result showed that the area under the curve(AUC)of serum CAⅢin diagnosing mild to moderate AD in elderly patients was 0.946,with sensitivity and specificity of 88.79% and 96.74%,respectively.Conclusions Serum CAⅢlevels in elderly patients with mild to moderate AD are higher than those in healthy individuals.Mild AD,without depressive mood,and elevated serum creatinine levels are related factors for elevated serum CAⅢlevels in elderly AD patients.Serum CAⅢmay serve as a novel biological marker for the diagnosis of mild to moderate AD in the elderly.

Objective To investigate the prognostic value of plasma thrombomodulin(TM)in patients with septic shock.Methods A retrospective analysis was conducted on the clinical data of 180 patients with septic shock admitted to the intensive care unit of the 908th Hospital from May 2018 to November 2022.The patients were divided into survival group(106 cases)and death group(74 ca-ses)based on the 30-day follow-up outcomes.Propensity score matching(PSM)was used to match 57 surviving patients with 57 de-ceased patients in a 1∶1 ratio,based on confounding factors such as age,gender,underlying diseases,primary infection site,laborato-ry results and disease severity scores.TM and other coagulation molecular markers were compared between the two groups,and logistic regression,receiver operating characteristic(ROC)curve,survival and correlation analyses were performed.Results After PSM,the TM levels in the death group(18.3[13.2,22.3]TU/mL)were significantly higher than those in the survival group(13.7[9.0,18.3]TU/mL)(P＜0.05).Multivariate logistic regression analysis showed that TM was an independent risk factor for 30-day mortality in the patients with septic shock(OR=1.137,95％CI:1.023-1.262,P＜0.005).ROC curve analysis revealed that the areas under the curve(AUCs)for predicting 30-day mortality were 0.665,0.627 and 0.600 for TM,Acute Physiology and Chronic Health EvaluationⅡ(APACHE Ⅱ)and Sequential Organ Failure Assessment(SOFA)scores,respectively.Kaplan-Meier survival analysis stratified by the optimal TM cut-off value(17.9 TU/mL)showed that the 30-day survival rate of the TM＜17.9 TU/mL group was 1.56 times that of the TM≥17.9 TU/mL group(Log-Rank test,P＜0.000 1).Spearman correlation analysis demonstrated that TM levels were positively correlated with APACHE Ⅱ(r=0.10,P＜0.005)and SOFA scores(r=0.35,P＜0.005).Conclusion Plasma TM has showed a good predictive value for assessing the prognosis of patients with septic shock and may serve as a potential biomarker for determining the prognosis of septic shock.

Objective:To investigate the facilitators and hindrances of smoking cessation in patients with chronic obstructive pulmonary disease (COPD), and to provide a basis for developing individualized smoking cessation intervention strategies for COPD patients.Methods:Based on the health ecology theory and using a phenomenological approach in qualitative research, purposive sampling was used to select 15 COPD patients with smoking history who were admitted to Tianjin Fourth Central Hospital from March to May 2023 and face-to-face semi-structured interviews were conducted. Colaizzi seven-step analysis was used to analyze the interview content.Results:A total of 15 COPD patients were interviewed, including 13 males and 2 females, aged 61-75 years old. The facilitators of smoking cessation in COPD patients included complications, sequelae of novel coronavirus infection, fear of death, smoking cessation counseling by medical staff, heavy family financial burden, and smoke-free environment. The hindrances of smoking cessation in COPD patients included milder disease symptoms of COPD, higher levels of nicotine dependence, false disease-related perceptions, family supervision and control, and occupational experience.Conclusions:Smoking cessation in COPD patients is influenced by five factors: personal characteristics, behavioral characteristics, interpersonal network, living and working conditions, and policy environment. Medical staff and relevant national institutions should formulate corresponding smoking cessation strategies according to address the facilitators and hindrances of smoking cessation in COPD patients, so as to further reduce the smoking prevalence of COPD patients, promote the health of patients and reduce the burden of disease.

Objective:To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy.Methods:Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers.Results:All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors.Conclusions:The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

This study aims to analyze the main drug resistance mechanism of Salmonella enteritidis induced by polymyxin in vitro.In this study,the resistance of Salmonella enteritidis CMCC(B)50335(ZK)to polymyxin was induced in vitro,and the growth characteristics,exercise ability,ul-trastructure and sensitivity to 16 antimicrobial agents before and after induction were determined by turbidimetry,semi-solid agar method,transmission electron microscope and disk diffusion method,and the whole genome and single nucleotide polymorphism(SNP)were detected by Illu-mina NovaSeq PE150 method.RT-qPCR was used to detect the differences in the expression levels of six drug-resistant related genes.The recombinant strain △phoPE1-128-1,which induced drug-resistant strain E1-128-1,was constructed by homologous recombination of Red Escherichia coli,and its sensitivity to polymyxin was detected.The results showed that three strains of induced drug-resistant bacteria E1-128-1,E1-128-3 and E2-128-3 were screened out,and the MIC increased by 128,64 and 64 times respectively after drug resistance stability test.Induced drug resistance had no significant effect on the growth ability of the tested bacteria and the sensitivity of 16 antibacte-rial drugs.The exercise ability of E1-128-1was significantly increased,and the cell wall and plasma membrane obviously thicken.There was no significant difference in the genome components of E1-128-1 before and after induction,but eight missense mutations of six drug-resistance related genes,including phoP/phoQ,cpxP,lptD,csrA and acrB,were detected,including four missense mutation sites of phoP,namely Leu185Trp,His189Ser,Thr190Tyr and Ile191His.The corresponding genes were sequenced by PCR,and the results were consistent with those of SNP.RT-qPCR results showed that the expression levels of mutant genes of the three induced strains increased signifi-cantly.Compared with E1-128-1,the MIC of △phoP E1-128-1 decreased to 1 mg/L.It is sug-gested that the mutation and increased expression of phoP gene are important factors for inducing polymyxin resistance of Salmonella CMCC(B)50335 in vitro.

ObjectiveTo compare the efficacy and safety of acupuncture combined with auricular acupoints patches and nicotine transdermal patch in treating moderate to severe nicotine dependence. MethodsIn a rando-mized controlled trial， 64 quit smoking voluntary subjects with moderate to severe nicotine dependence were randomly divided at a ratio of 1∶1 into a treatment group and a control group， with 32 cases in each group. The treatment group was given acupuncture combined with auricular acupoints patches， twice weekly， four weeks as a course for two courses. The control group was given nicotine transdermal patch， one patch per day for 24 hours， 8 weeks. The cure rate was assessed after treatment and at follow-up （the 16th week after treatment）.The daily smoking volume， exhaled carbon monoxide （CO） value， Nicotine Dependence Scale （FTND）， Minnesota Nicotine Withdrawal Symptoms Scale （MNWS）， and Pittsburgh Sleepiness Index Inventory （PSQI） were evaluated before and after treatment and at follow-up， and adverse effects were recorded. ResultsIn terms of the cure rate， there were both six cured cases （20%） after treatment and at follow-up in the treatment group， while in the control group， seven （23.3%） and five （16.7%） patients were cured after treatment and at follow-up， respectively， with no statistically significant differences between the two groups both after treatment and at follow-up （P＞0.05）. The daily smoking volume and exhaled CO value significantly decreased after treatment and at follow-up in both groups （P＜0.05）， but were not significantly different between the groups after treatment and at follow-up （P＞0.05）. After treatment and at follow-up， FTND， MNWS， and PSQI scores were significantly reduced in both groups compared with those before treatment （P＜0.05）. There was no statistically significant difference in the FTND scale scores between the two groups after treatment and at follow-up （P＞0.05）， while the MNWS and PSQI scale scores were lower in the treatment group than in the control group （P＜0.05）. ConclusionAcupuncture combined with auricular acupoint patches for moderate to severe nicotine dependence has comparable effect with the first-line drug nicotine patch in terms of increasing the cure rate and decreasing the degree of nicotine dependence， and is superior to nicotine patch in terms of relieving withdrawal symptoms and improving sleep， with stable long-term effect.

Objective:To investigate the changes in gray matter volume (GMV) and abnormalities in structural covariant network (SCN) patterns in patients with chronic pontine infarction (PI).Methods:Patients with unilateral chronic PI (case group) with the first onset admitted to the First Affiliated Hospital of Zhengzhou University and Tianjin Medical University General Hospital from October 2014 to June 2021 were prospectively included. At the same time, healthy subjects matched with age, gender and education years (normal control group) were included. High-resolution three-dimensional T 1 structural MRI images and behavioral scores of the subjects were collected. The voxel-based morphometry and two-sample t test were used to explore the differences in GMV between the groups. Using GMV differential brain regions as seed points, SCN was constructed to explore the abnormality of structural covariant patterns in patients with PI. Spearman rank correlation analysis was used to analyze the correlation between GMV in differential brain regions and behavioral scores. Results:A total of 60 patients with PI were enrolled, including 33 left PI and 27 right PI, while 34 healthy controls were also enrolled. Compared with the normal control group, the GMV in bilateral posterior cerebellar lobe decreased significantly in the left PI group, and the GMV in left anterior and posterior cerebellar lobes and the right posterior cerebellar lobe decreased significantly in the right PI group (Gaussian random field correction with voxel level P<0.001 and cluster level P<0.05, cluster voxel >20), and there was a significant correlation between GMV values in the left anterior and posterior cerebellar lobes and the right posterior cerebellar lobe and the motor function score ( P<0.05). In addition, compared with the normal control group, the right PI group had broader covariate brain regions and a significant increase in the number of structural connections between covariate brain regions (family-wise error correction with voxel level P<0.05, cluster voxel >20). Conclusions:The GMV in bilateral posterior cerebellar lobe decreases significantly in patients with chronic PI, and were secondary to broader covariate brain regions and structural connections. This may be the neural mechanism of impaired behavioral function in patients with PI.

Cohort study is one of the important research methods in analytical epidemiology because of its clear time sequence relationship, which is better than other observational studies in demonstrating causal association. However, screening diagnosis or other methods are often used to exclude the individuals with outcome events during the enrollment process of the subjects in cohort studies. The accuracy of screening diagnosis and the effectiveness of exclusion will affect the accuracy of the baseline status assessment of the subjects included in the study, which may lead to the causal time sequence reversal of exposure-outcome in the estimation of causal effect. Landmark analysis can be used to control reverse causality by excluding subjects with potentially unknown expose-outcome timing. In this paper, we describe the basic principles and analytical steps of landmark analysis, and use data from the Chinese Longitudinal Healthy Longevity Survey to explore the relationship between physical activity and frailty, and introduce the specific application of landmark analysis for the purpose of facilitating its application and inferring causal effects more accurately in cohort studies.