OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Objective To investigate the public health issues associated with the follow-up outcomes of mental health in elderly community residents with a focus on mild cognitive impairment （MCI） and emotional problems （anxiety and depression）， as the burden of various diseases increases with global population growth and aging. Methods In this study， Patient Health Questionnaire-9， Early Dementia Screening Scale， Montreal Cognitive Assessment， Generalized Anxiety Disorder Scale， Geriatric Depression Scale， and Activities of Daily Living scale were used to analyze the data on MCI and emotional problems among the elderly in a district of Shanghai， China. The t-test， Spearman correlation analysis， and linear regression analysis were used to identify related protective factors and evaluate the effectiveness of comprehensive intervention measures. Results The first session of intervention led to an improvement in cognitive impairment （P<0.001）. During the first session of intervention， exercise and skill training were very effective in improving cognitive impairment （r=0.71 and 0.68， P<0.001）， while group instruction and the distribution of educational materials failed to achieve an ideal effectiveness. The second session of intervention also had a significant effect on cognitive impairment （P<0.05）； however， the second session of intervention lacked a significant overall effect， and skill training remained the most effective intervention method （Pr=0.0344， P<0.05）. The research findings showed that the two sessions of community intervention were protective factors against MCI and depression， while they could not alleviate anxiety. Conclusion This study validates the effectiveness of follow-up intervention measures in improving cognitive function in elderly patients with MCI， which provide scientific prediction and reference for early screening， prediction， and follow-up intervention of elderly dementia and MCI at the community level.

Objective To investigate the current situation of home environment safety of the elderly in Changning District, identify the risk factors related to the fall of the home environment of the elderly, and take targeted rectification measures, so as to create a safer environment for the elderly. Methods A phased random sampling method was used to select 201 elderly households from 10 streets in Changning District. Community doctors conducted on-the-spot investigation and assessment to collect information, and Epidata3.1 was used to input data and SAS 9.2 was used for statistical analysis. Results The incidence of falls in the past year was 19.90%, and the score of environmental risk factors/the number of environmental risk factors in each family ranged from 0 to 25, with an average of 9 items (standard deviation of 4.71). The results of multivariate logistic regression analysis show that the high level of falling environment (the number of falling risk factors in home environment ≥12) is still an independent risk factor for falls of the elderly, except for the influence of age and the number of drugs taken (OR=3.835, 95% CI:1.718-8.561). Conclusion The environmental risk factors causing falls are common in the home environment of the elderly in the community. It is necessary to focus on improving the home environment, reducing the risk of falls for the elderly, and creating a safe and comfortable home environment for the elderly.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

ObjectiveTo analyze the clinical and epidemiological characteristics of confirmed cases of human monkeypox infection in Changning District， Shanghai， and to explore their clinical and epidemiological characteristics. MethodsClinical data from 10 reported cases of monkeypox in individuals residing in Changning District or identified by local medical institutions between July 20 and September 30， 2023， were collected. Epidemiological case investigations were conducted， and throat swabs， anal swabs， and rash swabs were collected by the treating medical institutions. Real-time fluorescence quantitative PCR was used for monkeypox virus nucleic acid testing， and descriptive epidemiological analysis was applied to analyze the epidemiological characteristics of the cases. ResultsAll 10 confirmed cases of human monkeypox infection were all young males with an average age of 35.4 years， all of whom belonged to the men who have sex with men （MSM） population， with no occupational clustering. The primary clinical symptoms included fever， rash， enlarged inguinal lymph nodes， and muscle soreness. Nine cases presented with a rash， and seven cases experienced fever symptoms. Among the 10 cases， one experienced fever， rash， enlarged lymph nodes， and muscle soreness； two had fever， rash， and enlarged lymph nodes； two had fever， rash， and systemic soreness； two had only a rash； one had fever or rash； and one was asymptomatic. Among the nine cases with a rash， the rash was mainly localized to the genital or anal area， with fewer cases presenting rashes on the limbs or trunk simultaneously. All cases reported a history of non-exclusive MSM behavior within 21 days before the onset of the disease. The interval between the last suspected high-risk exposure and the onset of symptoms was 4 to 10 days， with an average interval of 6.9 days. The time from the onset of fever to the appearance of a rash was 0 to 5 days， with an average of 1.87 days. ConclusionThe main clinical manifestations of human infection with monkeypox are fever， rash， and enlarged inguinal lymph nodes. The MSM population is a high-risk group for monkeypox infection， and its source of infection may be associated with MSM exposure. Early-stage symptoms are mild， leading to potential underdiagnosis. Additionally， patients may conceal information during the investigation process， which increases the difficulty of epidemic prevention and control.

ObjectiveTo investigate the high-risk detection rate and aggregation of cardiovascular diseases（CVD） in 8 districts of Shanghai and influencing factors， and to provide scientific references for prevention and control of CVD. MethodsBased on the Cardiovascular Disease Screening and Management Program in Shanghai from 2016 to 2021， 104 685 participants aged 35 to 75 in 8 districts of Shanghai were selected for analysis. χ² test and multivariate logistic regression were used for statistical analysis of the influencing factors of CVD and aggregation of CVD. ResultsThe proportion of high-risk CVD individuals in the population was 19.17%， including the high-risk individuals with hypertension （8.65%）， dyslipidemia （6.33%）， CVD history （5.58%）， and WHO assessed risk ≥20% types （2.69%）， respectively. Old age， overweight and obesity， central obesity， smoking， drinking， farmers， unmarried， and low family income were the risk factors of CVD， while high education level was the protective factor. In the participants， 16 323 people （81.34%） were classified as CVD high-risk groups； The number of aggregation of 1， 2 and ≥3 high risk types of CVD were 16 323（81.34%）， 3 236（16.13%）， 509（2.54%）， respectively. Old age， low education level， low annual family income， farmers， unmarried， smoking， drinking， overweight， obesity and central obesity were associated with the risk of aggregation of high risk types of CVD， and the correlation strength increased with the increase of aggregation types. ConclusionThe prevention and control of CVD in Shanghai should focus on the hypertension， elderly， overweight， obesity， central obesity， smoking， drinking， low educated， low family income， farmers and unmarried people， and targeted intervention measures should be taken to reduce the risk of CVD among residents.

Objective To investigate the prevalence and risk factors of cognitive impairment in the nursing home population in Changning District, Shanghai. Methods In this study, random cluster sampling method was used to select 570 elderly people from 5 nursing homes in Changning District. Multivariate logistic regression was used to analyze the risk factors influencing cognitive function. Results The total prevalence of cognitive impairment in Changning nursing home population was 22.5%. The prevalence rates of ≤80 and >80 age groups were 16.8% and 23.9%, respectively, and the prevalence rates of men and women were 19.2% and 23.9%, respectively. Multivariate analysis showed that age ≥ 80 years old (OR=1.839, 95% CI: 1.045~3.235), no habit of reading book or newspaper (OR=2.087, 95%CI: 1.282~3.398), limitation of daily activity ability (OR=1.577, 95% CI: 1.023~2.431), and having depressive symptoms (OR=2.809, 95% CI: 1.840~4.288) were all influencing factors for cognitive impairment. Conclusion More than one fifth of elderly people in nursing homes in Changning District have symptoms of cognitive impairment. It is necessary to carry out routine cognitive assessment and appropriate cognitive intervention for the nursing home population to reduce the health and economic losses caused by cognitive impairment.

OBJECTIVE: To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology. METHODS: TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice. RESULTS: Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05). CONCLUSION LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.
Mice ; Animals ; Toll-Like Receptor 4 ; Colitis-Associated Neoplasms ; Network Pharmacology ; Mice, Inbred C57BL ; Colonic Neoplasms/pathology*

[摘 要] 目的：探讨NOD样受体蛋白3（NLRP3）炎症小体的活化在子宫内膜异位症（EMT）进展为EMT相关性卵巢癌（EAOC）过程中的作用及其机制。方法：选取2018年4月至2019年6月上海市长宁区幼保健院收治的EAOC、EMT、正常子宫内膜（CON组）组织标本各15例及患者的临床资料，利用免疫组织化学染色法、WB法检测EAOC、EMT和CON组织中NLRP3、caspase-1和IL-1β及含BRCA1/BRCA2的复杂亚基3（BRCC3）的表达水平。构建过表达BRCC3质粒和si-NLRP3质粒并转染EMT细胞CRL-7566，通过WB法检测转染后细胞中BRCC3蛋白的表达水平，利用MTT法、流式细胞术及Transwell实验分别检测转染后细胞增殖、凋亡、迁移与侵袭能力的变化。对过表达BRCC3组细胞进行干扰NLRP3实验，通过WB法检测干扰后BRCC3和NLRP3蛋白的表达水平，检测干扰后细胞增殖、凋亡、迁移与侵袭能力的变化。结果：EAOC和EMT组织中NLRP3、caspase-1、IL-1β和BRCC3的表达水平较CON组均呈明显升高（均P<0.01），且EAOC组织中NLRP3与BRCC3的表达呈正相关（r=0.65，P<0.01）。在CRL-7566细胞中过表达BRCC3显著促进细胞的增殖、迁移和侵袭并抑制细胞凋亡（均P<0.01），敲减NLRP3则抑制CRL-7566细胞的上述表型（均P<0.01），过表达BRCC3增强NLRP3的表达水平（P<0.01），而干扰BRCC3则抑制NLRP3表达（P<0.01）；干扰NLRP3可以部分逆转BRCC3对细胞凋亡的抑制作用（P<0.01）、对细胞迁移（P<0.05）和侵袭（P<0.01）的促进作用。结论：EAOC和EMT组织中NLRP3和BRCC3均呈高表达，过表达BRCC3可促进CRL-7566细胞的增殖、迁移和侵袭并抑制细胞凋亡，与EMT向EAOC转化有关，BRCC3/NLRP3是潜在的EAOC炎癌转化预测标志物及治疗靶点。

ObjectiveTo evaluate the caries prevention effect of different fluoride application frequencies in 3-year-old children with active caries. MethodsA total of 337 3-year-old children with dental caries from 12 kindergartens in Changning District of Shanghai were divided into three groups： group 1 received fluoride application once every three months， group 2 received fluoride application once every six months， and the control group received no fluoride application. At baseline， parents completed a questionnaire survey， and oral examinations were conducted at baseline， 7 months， and 16 months after the fluoride intervention to assess the incidence of new dental caries， new dmft， and new dmfs of children. Multivariate logistic regression analysis was used to analyze the relationship between fluoride application and new dental caries， with new dental caries as the dependent variable and local fluoride application， child's gender， age in months， parents' highest education level， frequency of sugary intake （desserts， candies， sweet beverages）， age of toothbrushing initiation， frequency of daily toothbrushing， use of fluoride toothpaste， parental assistance in child’s toothbrushing， and daily use of dental floss as the independent variables. ResultsThere were no significant differences in baseline general conditions and oral health behaviors among group 1 （121 cases）， group 2 （123 cases） and the control group （93 cases） （all P>0.05）. After 16 months' intervention， three children were lost to follow-up due to transferring schools. The new caries rates of group 1 （120 cases）， group 2 （121 cases） and the control group （93 cases） were 5.83%， 24.79% and 52.69%， respectively. The incidence of new caries was significantly lower in group 1 compared to group 2 and the control group （P<0.001）， and it was also significantly lower in group 2 compared to the control group （P<0.001）. The newly-increased caries of group 1， group 2 and the non-fluoride control group were all 0.12 0.52， 0.36 0.68 and 1.16 1.39， respectively. The mean increment of new caries was lower in group 1 compared to group 2 （P=0.040） and the non-fluoride control group （P<0.001）， and it was lower in group 2 compared to the non-fluoride control group （P<0.001）. After adjusting for factors such as gender， parents' education level and child's oral health behaviors by multivariate logistic regression， the results showed that fluoride application once every three months could significantly reduce the risk of dental caries （OR=0.04， P<0.001）. ConclusionLocal use of fluoride has a certain effect on the prevention and treatment of dental caries in children with active caries. Fluoride application once every three months effectively reduces the incidence of new caries and slows down the progression of caries lesions. It is suggested that local application of fluoride should be implemented once every three months for children with active caries.