Syndrome differentiation and treatment is an integral part of the traditional Chinese medicine （TCM） diagnostic and therapeutic system， whose development exhibits distinct stages. This paper systematically reviews the evolutionary trajectory of syndrome differentiation and treatment， from symptom-based treatment in Inner Canon of Yellow Emperor （《黄帝内经》）， to ZHANG Zhongjing's establishment of the disease-pulse-syndrome-treatment framework， through its application and development in the Ming and Qing dynasties， and finally to its recognition as a fundamental characteristic of TCM in modern times. However， the overemphasis on syndrome differentiation and treatment， coupled with a diminished focus on disease concepts， has led to its gradual alienation as the primary diagnostic and therapeutic model. The alienation mainly manifests as a tendency to prioritize syndrome over disease， resulting in the overgeneralization and limited application of the concept， and causing a lack of specificity in practice. This paper emphasizes that a correct understanding of syndrome differentiation and treatment is a necessary premise for the deve-lopment and improvement of the TCM diagnostic and therapeutic system. By integrating modern medical diagnosis to clarify disease targets and applying TCM thinking to extract common patterns of diseases， precise alignment between syndrome differentiation and treatment and modern clinical demands can be achieved， providing a reference for addressing the contemporary challenges of syndrome differentiation and treatment.

To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic

Based on the traditional Chinese medicine （TCM）'s understanding of consumptive thirst disease and modern medicine's understanding of the etiology of diabetes mellitus and the evolution of the disease， this article discussed the rationality and clinical significance of using "sugar collateral disease" as the name of diabetes mellitus in TCM， to provide a reference for modernization and development of TCM diseases' names. It is argued that the clinical manifestations described in the TCM disease name of consumptive thirst disease are only at a certain stage of diabetes mellitus， and it is difficult to cover the clinical characteristics of modern diabetes mellitus comprehensively. In 2003， academician TONG Xiaolin proposed to use "sugar collateral disease" as the TCM disease name of diabetes mellitus， which on the one hand can reflect the essence of diabetes mellitus， and on the other hand can embody the disease location， disease mechanism and the evolution of the disease， highlight the harms of complications， and serve as a warning for the early diagnosis and treatment of the disease， which can help to enhance the level of diagnosis and treatment of diabetes mellitus in TCM.

Through the systematic analysis of the current research results on the effectiveness of traditional Chinese medicine（TCM） in the prevention and treatment of diabetes and its promotion dilemma， it is believed that cohort study， as an observational research method， is particularly suitable for evaluating complex and individualized interventions such as traditional Chinese medicine in the prevention and treatment of diabetes. Considering the design features and relevant practices of prospective cohort studies， it is specifically proposed to carry out prospective cohort studies using a modern TCM diagnostic and treatment system for diabetes， centered on "state-targeted differentiation and treatment"， and framed by "classification-staging-syndrome differentiation". Focused on personalized prevention and treatment， long-term multidimensional assessment of therapeutic effectiveness and syndrome changes， this paper gives in-depth exploration of the advantages and value of applying prospective cohort studies in the effectiveness evaluation of TCM in prevention and treatment of diabetes， aiming to provide insights for clinical researches on TCM for diabetes.

Objective To investigate the effect of ursodeoxycholic acid(UDCA)on the symptoms after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in patients with primary biliary cholangitis(PBC)and their family member.Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22,2023 and 128 family members,including demographic information,comorbidities,UDCA administration,SARS-CoV-2 infection,vaccination,symptoms,therapeutic medication,and the changes in liver disease-related symptoms.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results The median age was 51 years in the PBC patients and 49 years in the family members,with no significant difference between the two groups(P>0.05).Compared with the family member group,the PBC group had significantly lower body mass index(22.2±2.4 kg/m2 vs 23.3±2.9 kg/m2,P<0.001)and proportion of male individuals(10%vs 55%,P<0.001).All PBC patients received UDCA at a dose of 13—15 mg/kg,and SARS-CoV-2 infection rate was 100%in both groups.The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients(91%vs 57%,P<0.001).Compared with the family members,the PBC patients had significantly milder symptoms of sneezing,nasal obstruction,chest pain,and abnormal taste(P<0.05).Compared with the family members,the PBC patients had significantly lower rates of use of compound cold medicine(11%vs 20%,P<0.05)and Lianhua Qingwen capsules(12%vs 21%,P<0.05).For the PBC patients after SARS-CoV-2 infection,the liver disease-related symptoms such as fatigue,abdominal distension,dry mouth and dry eyes,pruritus,and yellow skin were aggravated by 37%,2%,27%,10%,and 3%,respectively.Conclusion Compared with the immediate family members of PBC patients who do not take UDCA,the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate,but UDCA may have a certain effect on alleviating infection-related symptoms in such patients.PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection,and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.

Objective:To seek a correlation between short-chain fatty acids (SCFAs) and skill in the activities of daily living (ADL) after an ischemic stroke.Methods:Ninety ischemic stroke survivors were assessed using the Barthel Index (BI). Fecal samples were collected and analyzed for the concentration of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid using gas chromatography. Spearman correlation analysis was conducted to identify SCFAs that correlated with the total BI score. Linear regressions were evaluated to explore the correlation between the total BI score and SCFAs.Results:The concentrations of propionic and butyric acids in the feces were found to correlate significantly with the total BI scores. Data including propionic acid and butyric acid levels, age, gender, body mass index, disease duration, any history of hypertension or diabetes, and other SCFAs were included in the regression models. Propionic and butyric acid levels were found to be potentially useful predictors of total BI scores.Conclusions:The concentration of propionic and butyric acids in the feces after an ischemic stroke can predict the survivor′s total BI score. Those concentrations could therefore be useful for predicting ADL ability.

Immunotherapy, which utilizes the body’s own immune system to fight cancer, has become one of the mainstream clinical strategies for cancer treatment, and the number of immunotherapeutic drugs approved for clinical treatment has increased year by year. However, the tumor microenvironment with immunosuppressive ability significantly reduces the effect of immunotherapy, making immunotherapy suffer from low response rate, poor penetration, and other problems, and the clinical efficacy is not ideal. In this review paper, the methods and mechanisms of action of remodeling the immunosuppressive tumor microenvironment (ITME) by reducing immunosuppressive cells and soluble molecules were summarized, and the important role of combined chemotherapy, radiotherapy, and other therapeutic modalities was explored in remodeling the ITME and enhancing the efficacy of immunotherapy.

Objective:The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored.Methods:The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot.Results:Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5′SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level.Conclusion:The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.