Mechanisms and Research Progress of Traditional Chinese Medicine Regulating NF-κB in the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.

Classification of metabolic-associated fatty liver disease subtypes based on TCM clinical phenotype

Objective:To classify the subtypes of metabolic-associated fatty liver disease(MAFLD)and provide new insights into the heterogeneity of MAFLD.Methods:Electronic medical records(EMR)of MAFLD diagnosed in accordance with the diagnostic criteria of Hubei Provincial Hospital of Traditional Chinese Medicine from 2016-2020 were included in the study.for physical annotation,and the data on each clinical phenotype was normalized according to corresponding aspirational standards.The MAFLD heterogeneous medical record network(HEMnet)was constructed using sex,age,disease diagnosis,symptoms,and Western medicine prescriptions as nodes and the co-occurrence times between phenotypes as edges.K-means clustering was used for disease classification.Relative risk(RR)was used to assess the specificity of each phenotype.Statistical methods were used to compare differences in laboratory indicators among subtypes.Results:A total of patients(12,626)with a mean age of 55.02(±14.21)years were included in the study.MAFLD can be divided into five subtypes:digestive diseases(C0),mental disorders and gynecological diseases(C1),chronic liver diseases and decompensated complications(C2),diabetes mellitus and its complications(C3),and immune joint system diseases(C4).Conclusions:Patients with MAFLD experience various symptoms and complications.The classification of MAFLD based on the HEMnet method is highly reliable.

Role of Cyclin D1b in Inducing Macrophages Toward a Tumor-associated Macrophage-like Phenotype in Murine Breast Cancer

Objective:Tumor-associated macrophages(TAMs)of the M2 phenotype are frequently associated with cancer progression.Invasive cancer cells undergoing epithelial-mesenchymal transition(EMT)have a selective advantage as TAM activators.Cyclin D1b is a highly oncogenic splice variant of cyclin D1.We previously reported that cyclin D1b enhances the invasiveness of breast cancer cells by inducing EMT.However,the role of cyclin D1b in inducing macrophage differentiation toward tumor-associated macrophage-like cells remains unknown.This study aimed to explore the relationship between breast cancer cells overexpressing cyclin Dlb and TAMs.Methods:Mouse breast cancer 4T1 cells were transfected with cyclin D1b variant and co-cultured with macrophage cells in a Transwell coculture system.The expression of characteristic cytokines in differentiated macrophages was detected using qRT-PCR,ELISA and zymography assay.Tumor-associated macrophage distribution in a transplanted tumor was detected by immunofluorescence staining.The proliferation and migration ability of breast cancer cells was detected using the cell counting kit-8(CCK-8)assay,wound healing assay,Transwell invasion assay,and lung metastasis assay.Expression levels of mRNAs were detected by qRT-PCR.Protein expression levels were detected by Western blotting.The integrated analyses of The Cancer Genome Atlas(TCGA)datasets and bioinformatics methods were adopted to discover gene expression,gene coexpression,and overall survival in patients with breast cancer.Results:After co-culture with breast cancer cells overexpressing cyclin D1b,RAW264.7 macrophages were differentiated into an M2 phenotype.Moreover,differentiated M2-like macrophages promoted the proliferation and migration of breast cancer cells in turn.Notably,these macrophages facilitated the migration of breast cancer cells in vivo.Further investigations indicated that differentiated M2-like macrophages induced EMT of breast cancer cells accompanied with upregulation of TGF-β1 and integrinβ3 expression.Conclusion:Breast cancer cells transfected with cyclin D1b can induce the differentiation of macrophages into a tumor-associated macrophage-like phenotype,which promotes tumor metastasis in vitro and in vivo.

Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μmol/L±270.09μmol/L vs 176.13μmol/L±185.70μmol/L,P=0.014).Serum albumin levels were significantly increased in both the"TQD"group and"TTK"group as compared with the MMC group(31.30 g/L±4.77g/L,30.72 g/L±2.89 g/L vs 28.57 g/L±4.56 g/L,P<0.05).There were no significant differences in levels of alanine transaminase among the three groups(P>0.05).Safety data showed that there was one case of stomachache in the"TQD"group and one case of gastrointestinal side effect in the"TTK"group.CONCLUSION:Treatment with"TTK"improved the survival rates of patients with liver failure due to chronic hepatitis B.Additionally,liver tissue was regenerated and liver function was restored.

Analysis of Clinical Features in Novel Coronavirus Pneumonia Convalescents

Background:To analyze the clinical features of convalescent individuals with novel coronavirus-infected pneumonia(novel coronavirus pneumonia)at rehabilitation station in Wuhan.Methods:712 patients in the convalescence period of novel coronavirus pneumonia isolated and observed at the rehabilitation station were investigated by collecting their basic data,clinical syndrome features,and tongue manifestations.The clinical syndrome features were analyzed based on guidelines of Diagnosis and Treatment Plan for Novel Coronavirus-infected Pneumonia(National Health Commission of the People’s Republic of China,7th Trial Edition).Results:Cough(24.86%),chest tightness and shortness of breath(23.17%),and fatigue(16.57%)were the main symptoms of patients in the convalescence period of novel coronavirus pneumonia.Their tongue appearance was mostly characterized by redness(88.65%),thick coating(67.25%),greasy coating(49.78%)and white coating(76.86%).Conclusion:Compared with the ordinary/mild patients,cough and anorexia symptoms were more common in the severe/critical patients.In convalescent patients,red and fat tongue with thick greasy fur were common.

Potential mechanism of Shugan Jieyu capsule in the treatment of hepatitis B based on network pharmacology

Objective:In this study,the effective components and related targets of Shugan Jieyu Capsule(SGJY)in the treatment of hepatitis B were determined to explore the mechanism of SGJY in the treatment of hepatitis B.Methods:In this study,the effective components and targets of SGJY,and the related targets of hepatitis B were searched,and obtained the targets of SGJY in the treatment of hepatitis B according to the principle of Venn diagram.To build a protein-protein interaction network,String database was used,Cytoscape(3.7.2)software was used for topology analysis,R(4.0.5)software was used for go analysis,KEGG pathway enrichment analysis,and study of putative signaling pathways to determine how they could work.Results:SZJY was used to predict a total of 11 Chinese herbal components and 85 associated targets for the treatment of hepatitis B.34 important targets were examined,including AKT1,EGFR,and 10 important pathways were examined,including proteoglycans in cancer and the PI3K/Akt signaling pathway.Conclusion:SGJY in the treatment of hepatitis B mainly inhibits the secretion of HBsAg and HBeAg by affecting PI3K-Akt and proteoglycans in cancer,and inhibits the progression of liver cancer.

Effect of traditional Chinese medicine combined with Western therapy on primary hepatic carcinoma： a systematic review with meta-analysis

Primary hepatic carcinoma （PHC） is a common malignant tumor in China. Cancer is comprehensively treated with various therapeutic regimes, including traditional Chinese medicine （TCM）. TCM has been widely used to improve the quality of fife, delay the time of cancer progression, and prolong the median survival time. This systematic review with meta-analysis aimed to assess the effect of TCM combined with Western therapy on primary hepatic carcinoma. A comprehensive literature search was conducted in six databases, including CNKI, VIP, Wan-Fang Database, CBM, PubMed, and Cochrane library. A total of 44 randomized controlled trials （RCTs） involving 3429 participants suffering from PHC were selected. Meta-analysis results indicated that the overall effect of TCM and Western integrative treatment on PHC was higher than that of Western intervention alone, which can postpone tumor recurrence and metastasis and prolong the overall survival time of patients with PHC. Although the obtained evidence remained weak because of the poor methodological quality of the included studies, this review provided relevant data supporting the efficacy and safety of TCM combined with Western therapies. In future research, individual RCT studies should incorporate accepted standards for trial design and reporting, proper outcome indicators according to international standards, blinding in allocation concealment, and valid follow-up periods.

Shumian capsule(舒眠胶囊) improves symptoms of sleep mood disorder in convalescent patients of Corona Virus Disease 2019

OBJECTIVE:To evaluate the clinical effectiveness of Shumian capsule(舒眠胶囊)in improving the symptoms of insomnia,anxiety,depression,and other symptoms of convalescent patients of COVID-19.METHODS:Totally 200 patients were collected and randomly divided into experiment group(n=100)and control group(n=100).The control group was treated with Shumian capsule simulator,and the experiment group was treated with Shumian capsule.The improvement of TCM symptom score,the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed,and the clinical effect was evaluated.RESULTS:One week after treatment,the scores of anxiety symptoms in the experiment group were significantly different from those in the control group(P<0.05),but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group(P>0.05).There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia,anxiety and depression between the experiment group and the control group(P>0.05).After 2 weeks of treatment,the scores of insomnia,anxiety,depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group(P<0.05).There was no significant difference in the disappearance rate of insomnia,anxiety and depression between the experiment group and the control group(P>0.05).There were no significant differences in heart rate,respiration,systolic blood pressure and diastolic blood pressure between the experiment group and the control group(P>0.05).CONCLUSION:Shumian capsule can significantly improve the symptoms of insomnia,anxiety and depression in COVID-19’s convalescent patients with sleep and mood disorders.

Microenvironment of Liver Regeneration in Liver Cancer

The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of ＂tonifying Shen（Kidney） to regulate liver regeneration and repair by affecting stem cells and their microenvironment＂ can regulate ＂the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration＂; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.

Mining intrinsic information of convalescent patients after suffering coronavirus disease 2019 in Wuhan

OBJECTIVE:To summarize the potential characteristics of convalescent patients with coronavirus disease 2019(COVID-19)in China based on emerging clinical tongue data and guide the treatment and recovery of COVID-19 patients from the perspective of Traditional Chinese Medicine tongue diagnosis.METHODS:In this study,we developed and validated radiomics-based and lab-based methods as a novel approach to provide individualized pretreatment evaluation by analyzing different features to mine the orderliness behind tongue data of convalescent patients.In addition,this study analyzed the tongue features of convalescent patients from clinical tongue qualitative values,including thick and thin,fur,peeling,fat and lean,tooth marks and cracked,and greasy and putrid fur.RESULTS:We included 2164 tongue images in total(34%from day 0,35.4%from day 14 and 30.6%from day 28)from convalescent patients.The significance results are shown as follows.Firstly,as the recovery time prolongs,the L average values of tongue and coat decrease from 60.21 to 57.18 and from 60.06 to 57.03 respectively.Secondly,the decrease of abnormality rate of tongue coat,included greasy tongue fur,putrid fur,teeth-mark,thick-thin fur,are of significant statistical difference(P<0.05).Thirdly,the average value of gray-level cooccurrence matrices increases from 0.173 to 0.194,the average value of entropy increases from 0.606 to 0.665,the average value of inverse difference normalized decrease from 0.981 to 0.979,and the average value of dissimilarity decrease from 0.1576 to 0.1828.The details of other radiomics features are describe in results section.CONCLUSIONS:Our experiment shows that patients in different recovery periods have a relationship with quantitative values of tongue images,including L color space of the tongue and coat radiomics features analysis.This relationship can help clinical doctors master the recovery and health of patients as soon as possible and improve their understanding of the potential mechanisms underlying the dynamic changes and mechanisms underlying COVID-19.

Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection

COVID-19 caused by SARS-CoV-2 infection has caused substantial morbidity and mortality worldwide and paralyzed the international economy.Understanding the magnitude and duration of the antibody response to SARS-CoV-2 is important to achieve a balance between curbing the pandemic and minimizing adverse effects on society.1 Although the antibody response to SARS-CoV-2 within 9 months has been extensively studied,2,3,4,5,6 little is known about the magnitude and kinetics of antibody responses for over 9 months.Moreover,with limited observations over 9 months(n<100),2,7,8 several studies have produced inconsistent conclusions about antibody dynamics,suggesting different rates of antiviral antibody positivity at the last follow-up.2,7,8 These studies have been limited by a lack of measurement of neutralizing antibodies(NAbs),7 of inclusion of mild or asymptomatic cases,2,8 and of further exploration of potential predisposing factors for antibody dynamics.2,7 Considering the individual heterogeneity(such as disease severity)8 and time-dependent nature1 of the immune response,in-depth characterization of SARS-CoV-2 antibody kinetics across disease severity groups over a long period is urgently needed.Therefore,we repeatedly tested IgM,IgG,viral spike protein receptor-binding dom(anti-RBD)IgG,and NAb titers in COVID-19 patients during a follow-up period of up to 10 months and explored potential predisposing factors of antibody titers during follow-up.

Analysis of the lower incidence of medullary thyroid cancer in China

To the Editor: Thyroid cancer, which is one of the most common diseases of the endocrine system, can be divided into four primary types, including papillary thyroid cancer (PTC) accounting for 80% to 90% of cases, follicular thyroid cancer accounting for 10% to 15% of cases, medullary thyroid cancer (MTC) accounting for 3% to 10% of cases, and anaplastic thyroid cancer accounting for 1% to 2% of cases. Typically, patients diagnosed with PTC or follicular thyroid cancer have better prognoses and overall survival rates than patients diagnosed with MTC or anaplastic thyroid cancer. The incidence of thyroid cancer has been rapidly growing in the world [Supplementary Figure S1, http://links.lww.com/CM9/A99].[1] During the last 20 years, China has experienced significant growth in the number of annual thyroid cancer diagnoses. According to the Dataset Records for National Central Cancer Registry of China, thyroid cancer incidences have steadily increased in China from 2010 to 2014, yet the mortality rate has remained stable during the same period [Supplementary Tables S1 and S2, http://links.lww.com/CM9/A99].

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response.To this end,a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted,and the participants were followed up at 3.3(Visit 1),9.2(Visit 2),and 18.5(Visit 3)months after SARS-CoV-2 infection.They were classified into three groups(no-vaccination(n=54),one-dose(n=62),and two-dose(n=92)groups)on the basis of the administration of inactivated vaccination.The neutralizing antibody(NAb)titers against the wild-type virus continued to decrease in the no-vaccination group,but they rose significantly in the one-dose and two-dose groups,with the highest NAb titers being observed in the two-dose group at Visit 3.The NAb titers against the Delta variant for the no-vaccination,one-dose,and two-dose groups decreased by 3.3,1.9,and 2.3 folds relative to the wild-type virus,respectively,and those against the Omicron variant decreased by 7.0,4.0,and 3.8 folds,respectively.Similarly,the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose.Results showed that the convalescents benefited from the administration of the inactivated vaccine(one or two doses),which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses.Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic,and vaccination guidelines and policies need to be updated.

Shugan Jieyu capsule(舒肝解郁胶囊) improve sleep and emotional disorder in coronavirus disease 2019 convalescence patients: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy of the Shugan Jieyu capsule(舒肝解郁胶囊) on improving sleep and emotional disorder during Coronavirus disease 2019(COVID-19) convalescence. METHODS: We conducted a randomized, double-blind, placebo-controlled trial, and recruit 200 COVID-19 convalescence patients and then divide the subjects into two groups respectively: the experimental group(n = 100) and the control group(n = 100). Patients in the control group were given doses as a placebo, while those in the experimental group were given Shugan Jieyu capsule.The investigators mainly observed the differences between the two groups before and after treatment in terms of the rate of reduction and the rate of efficiency in Hamilton Depression Scale(HAMD-17) total scores from baseline, and recorded the scores of Hamilton Anxiety Scale(HAMA), Patient Health Questionnaire-15(PHQ-15), Insomnia Severity Index(ISI) and Treatment Emergent Symptom Scale at 2 week, the 4 week and the 6 week respectively after treatment, and compared the differences between the groups. And the occurrence of adverse events was recorded. RESULTS: After 6-week treatment, there were statistically significant differences in the rate of reduction as well as efficiency in HAMD-17 scores, HAMA Total Scores, PHQ-15 Score, ISI Score from baseline in the experimental group and control group(P < 0.05). There were 4 adverse events in the experimental group and 1 in the control group. CONCLUSION: Shugan Jieyu capsule could significantly improve sleep and emotional disorder in patients during COVID-19 convalescence.