Although symptomatic treatment is widely applied in clinical practice， it is often regarded as a relatively low-level therapeutic method. Based on Traditional Chinese Medicine （TCM） state theory， the macroscopic， mesoscopic， and microscopic characterization parameters of TCM symptomatology are horizontally integrated， the full life cycle of states （pre-disease， incipient disease， manifest disease， post-disease） is vertically covered， and the cognitive system of "symptoms" is reconstructed from multiple dimensions. Accordingly， the application approach of symptomatic treatment at different state stages is proposed： implementing preventive intervention in the pre-disease state， strengthening the interception of disease progression in the incipient disease state， regulating dynamic development and treatment in the manifest disease state， and formulating a staged diagnosis and treatment strategy which focuses on functional rehabilitation in the post-disease state.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

ObjectiveTo investigate the differences in abnormal liver biochemical parameters in pregnant patients during the epidemic or non-epidemic period of coronavirus disease 2019 （COVID-19）. MethodsA retrospective analysis was performed for 539 pregnant women who were discharged from Department of Obstetrics， Peking University First Hospital， from October 2017 to March 2022 and had at least one abnormal liver biochemical parameter among alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBil）， and total bile acid. The patients in the epidemic period of COVID-19 and those in the non-epidemic period of COVID-19 were compared in terms of etiology， coagulation parameters， aminotransferases， bile acid， and renal function. The independent samples t-test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsAmong the patients discharged from Department of Obstetrics during the non-epidemic period of COVID-19， 262 had abnormal liver biochemical parameters， accounting for 1.46%， while 277 patients had abnormal liver biochemical parameters during the epidemic period of COVID-19， accounting for 1.73% among the patients discharged from Department of Obstetrics during the same period of time， and there was a significant difference between these two groups （χ²=3.947， P=0.047）. The etiological analysis of the patients with abnormal liver biochemical parameters during the two periods showed that there was no difference in the proportion of patients with four pregnancy-specific liver diseases （hyperemesis gravidarum， preeclampsia and eclampsia， intrahepatic cholestasis of pregnancy， and acute fatty liver of pregnancy）. As for the patients with abnormal liver biochemical parameters in pregnancy， there was no significant difference in the proportion of patients with normal creatinine and stimated glomerular filtration rate （eGFR） between the epidemic period and the non-epidemic period （86.78% vs 87.90%， χ²=0.141， P=0.708）. The patients with ALT≥5×upper limit of normal accounted for 7.94% in the epidemic period of COVID-19 and 9.54% in the non-epidemic period （χ²=0.433， P=0.511）， and the patients with severe cholestasis accounted for 7.75% in the epidemic period of COVID-19 and 9.27% in the non-epidemic period （χ²=0.392， P=0.531）. The proportion of patients with obstetric bleeding during the epidemic period of COVID-19 was significantly lower than that during the non-epidemic period （14.61% vs 24.19%， χ²=489.334， P<0.001）. ConclusionThere is no difference in the proportion of patients with pregnancy-specific liver diseases among the patients with abnormal liver biochemical parameters in pregnancy between the epidemic period and the non-epidemic period of COVID-19， and there is no change in the proportion of patients with normal creatinine and eGFR among these patients in the epidemic period of COVID-19.

At present,radiofrequency ablation(RFA)has already replaced medication therapy and become the first-line treatment option for patients with atrial fibrillation.Intraoperative cardiac tamponade is the most commonly-seen fatal complication,and,unfortunately,the absolute number of this pernicious event is increasing with the extensive use of RFA.Therefore,the full understanding of cardiac tamponade and timely management of cardiac tamponade are of great significance in clinical practice.This article reviews the diagnosis,rescue and treatment process,prognosis and prevention strategies of this complication.(J Intervent Radiol,2024,33:325-329)

Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.

The essence of asymptomatic syndrome differenciation is that the disease is in a special stage or state. To perform traditional Chinese medicine （TCM） diagnosis when there was no symptoms for differentiation is a key scientific issue in current TCM diagnosis and treatment. The reasons include limitations in doctor-patient behaviors and relationships， as well as limitations in cognitive thinking. To address such situations， the following strategies can be adopted from a thinking perspective，i.e. grasping the occurrence and development of diseases based on a holistic concept， using dialectical thinking to summarize the laws of diseases， integrating clinical practice with experiential thinking， and introducing new thinking modes through interdisciplinary collaboration. These strategies help TCM practitioners make accurate diagnoses in the absence of obvious symptoms， thereby providing better medical services for patients.

In the context of the complex and ever-changing spectrum of diseases, the traditional Chinese medicine compatibility of prescription and drugs is no longer able to fully meet the needs of clinical diagnosis and treatment. Therefore, this article is based on the diagnosis and treatment model of the combination of disease, syndrome, and symptom, combined with the development achievements of Western medicine, and explores the principles of formulating traditional prescriptions based on the combination of chief, deputy, assistant, and envoy. This article proposes a formulation principle of composing prescriptions with the diagnosis of syndrome as the chief, the diagnosis of disease as the deputy, the treatment of symptoms as the assistant, and the harmonization of medicine as the envoy. This forms a treatment plan with the core link of syndrome differentiation and treatment, disease differentiation and treatment, symptomatic treatment, detoxification, and efficacy enhancement. The purpose of this article is to address the current clinical challenges such as an increasing disease spectrum and the complexity of syndrome patterns and symptom clusters. It aims to provide new insights into traditional Chinese medicine clinical treatment plans and herbal formulation strategies, with the ultimate goal of improving the clinical effectiveness of traditional Chinese medicine.

Objective:Flotillin-2(FLOT2)is a prototypical oncogenic and a potential target for cancer therapy.However,strategies for targeting FLOT2 remain undefined.Post-translational modifications are crucial for regulating protein stability,function,and localization.Understanding the mechanisms and roles of post-translational modifications is key to developing targeted therapies.This study aims to investigate the regulation and function of lysine acetylation of FLOT2 in nasopharyngeal carcinoma,providing new insights for targeting FLOT2 in cancer intervention. Methods:The PhosphoSitePlus database was used to analyze the lysine acetylation sites of FLOT2,and a lysine acetylation site mutation of FLOT2[FLOT2(K211R)]was constructed.Nasopharyngeal carcinoma cells were treated with histone deacetylase(HDAC)inhibitor trichostatin A(TSA)and Sirt family deacetylase inhibitor nicotinamide(NAM).TSA-treated human embryonic kidney(HEK)-293T were transfected with FLOT2 mutant plasmids.Co-immunoprecipitation(Co-IP)was used to detect total acetylation levels of FLOT2 and the effects of specific lysine(K)site mutations on FLOT2 acetylation.Western blotting was used to detect FLOT2/FLAG-FLOT2 protein expression in TSA-treated nasopharyngeal carcinoma cells transfected with FLOT mutant plasmids,and real-time reverse transcription PCR(real-time RT-PCR)was used to detect FLOT2 mRNA expression.Nasopharyngeal carcinoma cells were treated with TSA combined with MG132 or chloroquine(CQ)to analyze FLOT2 protein expression.Cycloheximide(CHX)was used to treat HEK-293T cells transfected with FLAG-FLOT2(WT)or FLAG-FLOT2(K211R)plasmids to assess protein degradation rates.The BioGrid database was used to identify potential interactions between FLOT2 and HDAC6,which were validated by Co-IP.HEK-293T cells were co-transfected with FLAG-FLOT2(WT)/FLAG-FLOT2(K211R)and Vector/HDAC6 plasmids,and grouped into FLAG-FLOT2(WT)+Vector,FLAG-FLOT2(WT)+HDAC6,FLAG-FLOT2(K211R)+Vector,and FLAG-FLOT2(K211R)+HDAC6 to analyze the impact of K211R mutation on total lysine acetylation levels.In 6-0B cells,overexpression of FLOT2(WT)and FLOT2(K211R)was performed,and the biological functions of FLOT2 acetylation site mutants were assessed using cell counting kit-8(CCK-8),colony formation,and Transwell invasion assays. Results:The PhosphoSitePlus database indicated that FLOT2 has an acetylation modification at the K211 site.Co-IP confirmed significant acetylation of FLOT2,with TSA significantly increasing overall FLOT2 acetylation levels,while NAM had no effect.Mutation at the K211 site significantly reduced overall FLOT2 acetylation,unaffected by TSA.TSA decreased FLOT2 protein expression in nasopharyngeal carcinoma cells without affecting FLOT2 mRNA levels or FLOT2(K211R)protein expression in transfected cells.The degradation rate of FLOT2(K211R)protein was significantly slower than that of FLOT2(WT).The proteasome inhibitor MG132 prevented TSA-induced FLOT2 degradation,while the lysosome inhibitor CQ did not.BioGrid data suggested a potential interaction between FLOT2 and HDAC6,confirmed by Co-IP.Knockdown of HDAC6 in nasopharyngeal carcinoma cells significantly increased FLOT2 acetylation;co-transfection of HDAC6 and FLAG-FLOT2(WT)significantly decreased total lysine acetylation levels,whereas co-transfection of HDAC6 and FLAG-FLOT2(K211R)had no effect.Knockdown of HDAC6 significantly reduced FLOT2 protein levels without affecting mRNA levels.MG132 prevented HDAC6-knockdown-induced FLOT2 degradation.Knockdown of HDAC6 significantly accelerated FLOT2 degradation.Nasopharyngeal carcinoma cells transfected with FLOT2(K211R)showed significantly higher proliferation and invasion than those transfected with FLOT2(WT). Conclusion:The K211 site of FLOT2 undergoes acetylation modification,and HDAC6 mediates deacetylation at this site,inhibiting proteasomal degradation of FLOT2 and maintaining its stability and tumor-promoting function in nasopharyngeal carcinoma.

Objective To explore the influence of gender on the prognosis of patients with atrial fibrillation(AF)undergoing left atrial appendage occlusion(LAAO).Methods All non-valvular AF patients who were admitted in our hospital and underwent LAAO from August 2014 to August 2021 were enrolled and grouped according to gender.Their general information,including gender,age,comorbid underlying diseases,and results of transthoracic echocardiography and transesophageal echocardiography(TEE)were collected.The incidences of device-related thrombosis(DRT),pericardial tamponade,stroke,bleeding,hospitalization for heart failure,and cardiac death were recorded during follow-up.The influence of gender on the prognosis of these patients was analyzed.Results There were totally 673 patients with non-valvular AF were enrolled,including 366 males and 307 females,at a mean age of 68.2±9.4 years.When compared with the male patients,the female ones had a higher CHA2DS2-VASc score(P＜0.01),but smaller proportions of history of stroke,average compression ratio of occluders,and incidence of residual shunt(＜3 mm)after occlusion(P＜0.05).In 45～60 d after surgery,TEE revealed that there were 17 cases of DRT,including 8 males(2.2％)and 9 females(2.9％),though without statistical difference between the groups.Among the 17 DRT cases,1 experienced stroke,and the incidence of stroke was 5.9％in those with DRT and 0.5％without.There were 4 cases of postoperative pericardial tamponade,including 1 in the male group and 3 in the female group(no significant difference),and all of them were improved after pericardial puncture and fluid extraction.During the follow-up period of 40.2±20.5 months,no obvious differences were observed between the 2 groups in terms of stroke,bleeding,hospitalization for heart failure,and cardiogenic death.Conclusion Gender shows no significant effect on the prognosis of patients with non-valvular AF after LAAO.