Immunotherapy, including immune checkpoint inhibitors, tumor vaccine therapy, oncolytic virotherapy, and adoptive cell therapy, has made remarkably breakthroughs in the field of oncology. Immune checkpoint inhibitors, which block programmed death receptor 1 or programmed death ligand 1, have been included in the first-line clinical treatment for advanced solid tumors, such as non-small cell lung cancer and malignant melanoma. However, primary or secondary drug resistance in tumors severely limits the survival benefits for patients. Immune-related adverse reactions, such as pneumonia, hypothyroidism, hypophysitis, and myocarditis, also greatly affect the quality of life of patients. Fuzheng Jiedu Huayu is an important concept guiding the prevention and treatment of tumors with traditional Chinese medicine (TCM). It is also a curative principle and therapeutic TCM method to reduce the toxicity and enhance the efficacy of immunotherapy. This article summarizes the research progress of immunotherapy and discusses how TCM reduces the toxicity and enhances the efficacy of immunotherapy, hoping to provide a reference for the integrated treatment of tumors with TCM and immunotherapy.

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor with insidious early symptoms and a poor prognosis.In traditional Chinese medicine(TCM),ESCC is classified as"ye ge."Drawing on clinical experience,we believe that kidney deficiency leads to the deficiency of vital qi and immune dysfunction,providing the foundation for cancerous growth by depleting qi and damaging essence,toxic stasis and stagnation,forming a local hypoxic and acidic microenvironment that promotes tumor invasion,metastasis,and recurrence.Considering the effect of modern comprehensive treatments,the occurrence and development of ESCC are summarized as kidney deficiency being the root cause and toxic stasis being the driving force.The pathogenesis and treatment of ESCC in the preoperative,postoperative,and non-surgical treatment stages are discussed.The pathogenesis of the disease is summarized as follows:preoperatively,toxicity and stasis intertwine,depleting the kidney;postoperatively,the kidney loses its vitality,allowing various pathogenic factors to persist;during non-operative treatment,vital qi and pathogens contend,resulting in entrenched toxicity.During the preoperative neoadjuvant phase,therapy should resolve stasis,eliminate toxins,enhance kidney function,tonify essence,and support the body.During the postoperative adjuvant phase,therapy should strengthen the root and consolidate the foundation while detoxifying and expelling stasis.The non-surgical treatment stage uses"balanced interruption,"targeting tumor progression and metastasis by harmonizing yin and yang,thus preventing recurrence.This article will provide insights into the integrative Chinese-Western management of ESCC.

Objective To analyze the predictive value of patient-reported outcomes(PRO)com-bined with hematological indicators for moderate-to-severe endoscopic activity in patients with ulcera-tive colitis(UC).Methods Clinical data of UC patients were retrospectively collected,including PRO,hematological parameters and endoscopic findings.Based on the Mayo endoscopic score,pa-tients were divided into remission and mild activity group(＜2 points)and moderate-to-severe activity group(≥ 2 points).Independent influencing factors for moderate-to-severe endoscopic activity were screened through multivariate Logistic regression analysis,and a binary Logistic regression model was constructed.The receiver operating characteristic(ROC)curve was used to evaluate the discriminato-ry ability of the predictive model.The calibration of the model was assessed using calibration curves and the Spiegelhalter Z-test,and the model's performance was further validated in an external valida-tion cohort.Results Rectal bleeding(RB),C-reactive protein/albumin(CAR)and erythrocyte sed-imentation rate(ESR)were independent influencing factors for moderate-to-severe endoscopic activity(P＜0.05).The area under the curve(AUC)of the nomogram predictive model constructed based on the logistic regression analysis results was 0.848(95％CI,0.798 to 0.900),with sensitivity of 76.6％and specificity of 79.6％.In the external validation cohort,the model's AUC was 0.778(95％CI,0.699 to 0.857),and there was no statistically significant difference compared with the AUC of the training cohort model(P＞0.05).In both the training and validation cohorts,the Spiegelhalter Z-test results indicated that the model had good goodness-of-fit(P＞0.05).Conclu-sion RB,CAR and ESR are independent influencing factors for moderate-to-severe endoscopic ac-tivity in UC patients.The combination of RB,CAR and ESR has high predictive value for moderate-to-severe endoscopic activity in UC patients,with good discriminatory and calibration abilities.

Objective:To explore the mechanism of Coicis Semen in treating non -small cell lung cancer combined with network pharmacology and in vitro cell experiment.Methods:The components and potential targets of Coicis Semen were obtained from TCMSP, and NSCLC related targets were collected from Genecards and Drugbank. They were intersected to get common targets. An intersection target PPI network was constructed using STRING database. GO function and KEGG pathway enrichment analysis were performed using DAVID database. A "disease-drug component-target" network was constructed using Cytoscape 3.8.0. The CCK-8 method was used to screen the concentration of Coicis Semen, and the cells were randomly divided into control group, Coicis Semen low-concentration group (0.125 mg/ml), Coicis Semen high-concentration group (0.25 mg/ml), Coicis Semen low concentration+FoxO1 inhibitor group, and FoxO1 inhibitor group (50 μmol/L) using a random number table. Cell proliferation ability was determined using CCK-8 method, and cell migration and invasion ability were detected using cell scratch assay and Transwell cell invasion assay. Western blot was used to detect the expression of FoxO1, cofilin-1, and p-cofilin-1 proteins.Results:A total of 9 active components and 246 targets were screened from Coicis Semen, 1 074 targets related to non-small cell lung cancer, and 11 intersecting targets were identified. The key targets of Coicis Semen in the treatment of non-small cell lung cancer were MAPK1, MAPK8, MAPK14, CDK2, INSR, AR, FGFR2, PGR, DHFR, and PLAU; GO functional enrichment analysis showed that Coicis Semen had an impact on the cellular, molecular, and biological functions of A549 cells; KEGG pathway enrichment analysis showed that the pathways of Coicis Semen in treating non-small cell lung cancer mainly focus on FoxO pathway, MAPK pathway, prostate cancer pathway, Ras pathway, etc. Compared with the control group, the proliferation rate, migration rate, and invasion number of A549 cells in the low and high concentration groups of Coicis Semen decreased ( P<0.05), p-cofilin-1 expression decreased ( P<0.05), and FoxO1 expression increased ( P<0.05). Conclusion:Coicis Semen can treat non-small cell lung cancer by regulating MAPK1, MAPK8, and MAPK14 targets, and acting on pathways such as the FoxO and MAPK pathways.

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor with insidious early symptoms and a poor prognosis.In traditional Chinese medicine(TCM),ESCC is classified as"ye ge."Drawing on clinical experience,we believe that kidney deficiency leads to the deficiency of vital qi and immune dysfunction,providing the foundation for cancerous growth by depleting qi and damaging essence,toxic stasis and stagnation,forming a local hypoxic and acidic microenvironment that promotes tumor invasion,metastasis,and recurrence.Considering the effect of modern comprehensive treatments,the occurrence and development of ESCC are summarized as kidney deficiency being the root cause and toxic stasis being the driving force.The pathogenesis and treatment of ESCC in the preoperative,postoperative,and non-surgical treatment stages are discussed.The pathogenesis of the disease is summarized as follows:preoperatively,toxicity and stasis intertwine,depleting the kidney;postoperatively,the kidney loses its vitality,allowing various pathogenic factors to persist;during non-operative treatment,vital qi and pathogens contend,resulting in entrenched toxicity.During the preoperative neoadjuvant phase,therapy should resolve stasis,eliminate toxins,enhance kidney function,tonify essence,and support the body.During the postoperative adjuvant phase,therapy should strengthen the root and consolidate the foundation while detoxifying and expelling stasis.The non-surgical treatment stage uses"balanced interruption,"targeting tumor progression and metastasis by harmonizing yin and yang,thus preventing recurrence.This article will provide insights into the integrative Chinese-Western management of ESCC.

BACKGROUND:Recent studies have shown that connective tissue growth factor not only participates in the development of neurons,but also participates in the pathogenesis of neurodegenerative diseases,depression,epilepsy,etc.It can also be used as a therapeutic target to develop related drugs,thereby improving the patients'quality of life. OBJECTIVE:To summarize the biological functions of connective tissue growth factor and the mechanisms involved in neurodegenerative diseases and depression,as well as the progress in intervention with connective tissue growth factor and related emerging treatments. METHODS:The first author searched relevant articles published from January 1996 to December 2022 in PubMed and Web of Science.The key words were"connective tissue growth factor,nervous system,depression,Alzheimer disease,epilepsy,Parkinson disease,epilepsy,amyotrophic lateral sclerosis,FG-3019"in English.After reading,screening and sorting,the articles consistent with the content of the review were collected.Finally,51 articles were selected for review. RESULTS AND CONCLUSION:Connective tissue growth factor participates in multiple biological activities such as fibrosis,cell adhesion,and cell development under different conditions through four different structural domains.Connective tissue growth factor is up-regulated in lesion sites of neurodegenerative diseases,depression and epilepsy.After interfering with the expression of connective tissue growth factor,the symptoms improve or disappear,suggesting that connective tissue growth factor plays an important role in the progression of these diseases.The development of novel therapeutic strategies and intervention targets around connective tissue growth factor is very promising therapeutic research.More research is needed to identify the mechanism of action to transfer from basic medical studies to clinical studies and to achieve safer and more effective treatments.

Objective:To compare the surgical efficacy of pericardial soft ring tricuspid valvuloplasty with DeVega and artificial valvuloplasty.Methods:227 patients undergoing tricuspid valvuloplasty due to rheumatic heart disease complicated with functional tricuspid valve insufficiency were retrospectively analyzed and divided into 3 groups according to tricuspid valvuloplasty dynamic cohort(pericardial ring group, 89 cases; the artificial flap ring group, 61 cases, and the DeVega group, 77 cases) were matched 1∶1 for propensity score(match A: pericardial ring group and artificial flap ring group; match B: pericardial ring group and DeVega group), the successful matching was included in follow-up and data collection, and cases with incomplete case data during follow-up were removed from the study cohort in pairs according to matching conditions. The results of follow-up 1 month, 6 months and 24 months after surgery were compared.Results:1 month after operation: the tricuspid valve regurgitant in all groups was significantly reduced or even disappeared compared with that before operation, and the right atrium and right ventricle were also smaller than that before operation, with statistical significance( P<0.05). 6 months after surgery: There was no statistical significance in the area of tricuspid regurgitation and right atrial/indoor diameter between all groups compared with the results one month after surgery( P>0.05), and there was no statistical significance in the recurrence rate of tricuspid regurgitation between all groups( P>0.05). 24 months after surgery: There were no significant differences in the recurrence rate of tricuspid regurgitation, area of tricuspid regurgitation and right atrial/indoor diameter between the two groups in matching A( P>0.05). There was no statistical significance in the right atrial/indoor diameter between the matched pericardial ring group and the Devega group, but the tricuspid valve regurgentation area of the Devega group at 24 months after surgery was higher than that of the Devega group at 1 month after surgery, and the difference was statistically significant( P<0.05). The regurgitation area and recurrence rate of tricuspid valve were significantly higher than those of pericardium-TVP group( P<0.05). Conclusion:Pericardial soft ring tricuspid valvuloplasty can effectively correct functional tricuspid valvuloplasty and reverse right heart remodeling, which is an effective tricuspid valvuloplasty.

Objective:To observe the neuroanatomical properties of the projection pathway from the nucleus reuniens(Re)to the dorsal(dHC)and ventral(vHC)hippocampus.Methods:Adeno-associated virus SV40 was injected into the Re of C57BL/6 mice and the profile of downstream projection in the whole brain was examined and ranked.Retro-grade tracer Fluoro-Gold(FG)was injected into the whole hippocampus(wHC),dorsal hippocampus(dHC)or ven-tral hippocampus(vHC),and the distribution of the retrogradely labeled neurons and its relationship with calretinin(CR)in the Re were analyzed.Results:After injection of SV40 virus into the Re,we observed projection fibers or ter-minals in 18 areas across the brain.Among the areas,those to the hippocampus(HC)were mainly distributed in the dorsal and ventral lacunosum molecular layer,which ranked No.2 with regard to the projection intensity.Following injection of FG into the hippocampus,we observed that the retrogradely labeled neurons projecting to the wHC were densely distributed in the rostrocaudal segments of Re,with a more concentrated aggregation in the ventromedial part.FG+CR+double labeled neurons accounted for(47.47±0.07)％of FG labeled neurons,and for(67.13±0.10)％of CR+neurons in this case.The retrograde labeled neurons projecting to the dHC were sparse and mainly distributed in the dorsolateral part of Re.FG+CR+double labeled neurons accounted for(24.11±0.06)％of FG labeled neurons,and for(32.99±0.19)％of CR+neurons.The retrogradely labeled neurons projecting to the vHC were mainly distrib-uted in the ventralmedial part of Re.FG+CR+double labeled neurons accounted for(49.55±0.03)％of FG labeled neurons,and for(69.14±0.12)％of CR+neurons.Conclusion:Hippocampus is an essential target of the Re.The projections to the dHC and vHP differ in the location of projection neurons and the positive ratio with CR,which may re-flect the differential pathophysiological functions of the two pathways in vivo.

Objective:To observe the neuroanatomical properties of the projection pathway from the nucleus reuniens(Re)to the dorsal(dHC)and ventral(vHC)hippocampus.Methods:Adeno-associated virus SV40 was injected into the Re of C57BL/6 mice and the profile of downstream projection in the whole brain was examined and ranked.Retro-grade tracer Fluoro-Gold(FG)was injected into the whole hippocampus(wHC),dorsal hippocampus(dHC)or ven-tral hippocampus(vHC),and the distribution of the retrogradely labeled neurons and its relationship with calretinin(CR)in the Re were analyzed.Results:After injection of SV40 virus into the Re,we observed projection fibers or ter-minals in 18 areas across the brain.Among the areas,those to the hippocampus(HC)were mainly distributed in the dorsal and ventral lacunosum molecular layer,which ranked No.2 with regard to the projection intensity.Following injection of FG into the hippocampus,we observed that the retrogradely labeled neurons projecting to the wHC were densely distributed in the rostrocaudal segments of Re,with a more concentrated aggregation in the ventromedial part.FG+CR+double labeled neurons accounted for(47.47±0.07)％of FG labeled neurons,and for(67.13±0.10)％of CR+neurons in this case.The retrograde labeled neurons projecting to the dHC were sparse and mainly distributed in the dorsolateral part of Re.FG+CR+double labeled neurons accounted for(24.11±0.06)％of FG labeled neurons,and for(32.99±0.19)％of CR+neurons.The retrogradely labeled neurons projecting to the vHC were mainly distrib-uted in the ventralmedial part of Re.FG+CR+double labeled neurons accounted for(49.55±0.03)％of FG labeled neurons,and for(69.14±0.12)％of CR+neurons.Conclusion:Hippocampus is an essential target of the Re.The projections to the dHC and vHP differ in the location of projection neurons and the positive ratio with CR,which may re-flect the differential pathophysiological functions of the two pathways in vivo.

This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). : Firstly，estimate the daily new infection rate in Wuhan before January 23，2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 to January 30th if the lockdown measure had been delayed for 7 days，assuming that the daily new infection in Wuhan after January 23 increased in a high，moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that，calculate the number of infection cases imported from Wuhan during this period. Finally，predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. : The daily new infection rate in Wuhan was estimated to be 0.021%，0.026%，0.029%，0.033% and 0.070% respectively from January 19 to January 23. And there were at least 20 066 infection cases in Wuhan by January 23，2020. If Wuhan lockdown measure had been delayed for 7 days，the daily new infection rate on January 30 would have been 0.335% in the exponential growth model，0.129% in the linear growth model，and 0.070% in the logarithm growth model. Correspondingly，there would have been 32 075，24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China，and the number of cumulative confirmed cases as of March 19 in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.
COVID-19 ; China/epidemiology* ; Cities ; Communicable Disease Control ; Humans ; SARS-CoV-2