ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription （QHJ） on colitis-associated colorectal cancer （CAC） in mice， and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal， model， QHJ low-dose （QHJ-L， 10 g·kg^-1）， and QHJ high-dose （QHJ-H， 40 g·kg^-1） groups. Azoxymethane （AOM） and dextran sodium sulfate （DSS） were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5^th week to the 14^th week， once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate， colon length， weight， and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling （Wnt3a）， β-catenin， Non-phosphor-β-catenin （Non-p-β-catenin）， and cholesterol-binding glycoproteins 133 （CD133） were detected by Western blot. The localization and expression of the cluster of differentiation （CD） 80 and CD11 antigen-like family member B （CD11b） were detected by immunohistochemistry （IHC）. The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group， the expression levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in colon tissues in the model group were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased （P<0.01）， and the protein levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in the QHJ-H group were significantly decreased （P<0.05， P<0.01）. Meanwhile， the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased （P<0.05， P<0.01）. Compared with those in the model group， CD11b in QHJ-L and QHJ-H groups was significantly decreased， and CD80 was significantly increased（P<0.05， P<0.01）. The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased， while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids （P<0.01）. ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice， the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.

Objective To investigate the effect and mechanism of sodium ferulate in the treatment of Ménière disease(MD)model mice.Methods BALB/c mice were selected,and an MD model was constructed using posterior fossa epidural approach combined with intraperitoneal injection of aldosterone.Sixty model mice were randomly grouped into the model group,the low dose sodium ferulate group,the medium dose sodium ferulate group,the high dose sodium ferulate group and the dexamethasone group,with 12 mice in each group.Another 12 BALB/c mice were selected as the sham operation group.After grouping and tympanic administration,auditory evoked brainstem response(ABR)was applied to detect the hearing level of mice in each group.HE staining and magnetic resonance imaging(MRI)were applied to observe the morphology of cochlea and membranous labyrinth hydrops of mice in each group.Enzyme-linked immunosorbent assay was applied to detect serum levels of lipoprotein a[Lp(a)],pro-inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in each group.Immunohistochemical staining and Western blot assay were applied to detect the expression of Lp(a)in each group.Results Compared with the sham operation group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,serum levels of Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly increased in the model group(P＜0.05).Compared with the model group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,levels of serum Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly decreased in the low,medium and high dose sodium ferulate groups and the dexamethasone group(P＜0.05),and the effect of high dose sodium ferulate was more obvious.Conclusion Sodium ferulate can down regulate the expression of Lp(a)protein,reduce the production of proinflammatory factors,inhibit the inflammatory reaction,thereby alleviating the symptoms of membranous labyrinth hydrops in MD mice,and improving their auditory function.

Objective:To investigate the risk factors of pulmonary invasive fungal disease (IFD) in patients with primary non-small cell lung cancer (NSCLC) after radiotherapy and to construct predictive model.Methods:A total of 298 patients with primary NSCLC who received radiotherapy in the Second People's Hospital of Yibin of Sichuan from January 2020 to January 2024 were retrospectively included as the study objects. The incidence of pulmonary IFD after radiotherapy was analyzed. Univariate and multivariate analyses were performed on the risk factors of pulmonary IFD in patients with primary NSCLC after radiotherapy. A logistic prediction model was constructed according to the results of multivariate analysis, and the predictive efficacy of each index was evaluated by receiver operator characteristic (ROC) curve.Results:There were 61 cases with pulmonary IFD after radiotherapy in all 298 patients, with the incidence of 20.47%. And 73 strains fungi were detected, including 57 strains for Candida and 16 strains for Aspergillus. There were statistically significant differences in age ( χ2=23.13, P<0.001), whether they had type 2 diabetes ( χ2=19.28, P<0.001), whether they underwent invasive procedures ( χ2=17.49, P<0.001), and concurrent chemoradiotherapy ( χ2=18.48, P<0.001) between IFD patients and non-IFD patients. Multivariate analysis showed that age≥65 years ( OR=4.64, 95% CI: 2.12-10.13, P<0.001), combined type 2 diabetes ( OR=5.63, 95% CI: 2.19-14.48, P<0.001), concurrent chemoradiotherapy ( OR=3.73, 95% CI: 1.74-8.02, P=0.001) and invasive procedures ( OR=5.11, 95% CI: 2.33-11.19, P<0.001) were independent risk factors for pulmonary IFD in patients with primary NSCLC after radiotherapy. Based on the above indexes, the logistic prediction model was constructed as follows: logit ( P) =-4.59+1.53×age+1.73×combined type 2 diabetes+1.32×concurrent chemoradiotherapy+ 1.63×acceptance of invasive procedures ( R2=0.852). ROC curve analysis showed that the area under the curve of pulmonary IFD in patients with primary NSCLC who were≥65 years old, combined with type 2 diabetes, receiving invasive procedures, concurrent chemoradiotherapy, and regression model P value were 0.68, 0.63, 0.68, 0.68, 0.82, respectively. Conclusion:The incidence of pulmonary IFD in patients with primary NSCLC after radiotherapy is independently related to age, type 2 diabetes, invasive procedures and concurrent chemoradiotherapy. The prediction model constructed by using the above four factors has good efficacy in predicting IFD in patients' lungs.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Objective To screen the differentially expressed proteins in glomeruli during the treatment of lupus nephritis(LN)with hydroxychloroquine sulfate(HCQ).Methods Sixty female NZB/WF1 mice were used.At the age of 28 weeks,40 mice with proteinuria of 3+to 4+were divided into HCQ and control groups.After feeding for 36 weeks,the glomerular proteins were extracted by magnetic beads and analyzed by two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ioniza-tion time-of-flight mass spectrometry(MALDI-TOF-MS).The expression of the candidate proteins in the glomeruli of the LN mice was exa-mined by immunohistochemistry.Results A total of 31 differentially expressed proteins were identified between the two groups,including 24 upregulated and seven downregulated proteins.Conclusion The expression of proteins like RI and ENOA in the glomeruli of LN mice was significantly different during HCQ treatment.These proteins may be involved in the pathogenesis of LN and are therefore potential targets of HCQ in the treatment of LN.

Objective:To analyze the features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected with other common respiratory pathogens among coronavirus disease 2019 (COVID-19) patients in Shanghai City, and to provide a reference for scientific prevention and control of COVID-19 and other respiratory infectious diseases.Methods:Descriptive epidemiological approaches were used to analyze the data of COVID-19 reported cases in Shanghai City from January 2020 to February 2021 in the information system of Chinese Disease Prevention and Control. Clinical data of the participants were collected, and their SARS-CoV-2 nucleic acid-positive respiratory specimens were collected at the time of illness onset or admission. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the 22 respiratory pathogens. Independent-samples t test was used for statistical analysis. Results:Of the 272 patients with COVID-19, 15(5.5%) had co-infection of SARS-CoV-2 with other respiratory pathogens, all of which were double infection. There were three cases infected with enterovirus/rhinovirus, two of each with adenovirus, human metapneumovirus and coronavirus NL63/HKU1, and one of each with coronavirus 229E, influenza A virus H1N1, parainfluenza virus 1 and respiratory syncytial virus B. Two cases infected with Mycoplasma pneumoniae. Among the 272 COVID-19 patients, 212(77.9%) had fever, 117(43.0%) had cough, 46(16.9%) had fatigue, and 35(12.9%) had sore throat. The white blood cell count of co-infection cases was higher than that of non-co-infection cases ((6.8±1.7)×10 9/L vs (5.3±1.6)×10 9/L), and the difference was statistically significant ( t=3.09, P=0.008). Conclusions:There is a certain proportion of co-infection of SARS-CoV-2 with other respiratory pathogens among the COVID-19 cases in Shanghai City, mainly viral pathogens, especially enterovirus/rhinovirus. A rational combination of drugs was recommended to improve the cure rate. Surveillance of acute respiratory infection should be further strengthened as well.

Klebsiella pneumoniae is one of the common pathogens causing hospital-acquired infection. With the wide use of carbapenem in recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged around the world. Carbapenemase production is the main cause of resistance to carbapenem antibiotics in Klebsiella pneumoniae. More than 70% of Klebsiella pneumoniae strains produce carbapenemase. Ceftazidime/avibactam (CAZ/AVI) can effectively treat CRKP infection, especially those caused by CRKP that can produce Klebsiella pneumoniae carbapenemase (KPC) or oxaclillinase (OXA)-48. However, it has been reported that CAZ/AVI-resistant CRKP strains have emerged. In this paper, the epidemiology, risk factors, resistance mechanism and treatment of CAZ/AVI-resistant CRKP were summarized to provide reference for clinical treatment.

ObjectiveTo isolate and study the biological characteristics of severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） from feces of coronavirus disease 2019 （COVID-19） patients. MethodsVero E6 cells were used for virus isolation and the isolated strains were tested by nucleic acid test， immunofluorescence test， virulence test and whole genome sequencing. 50% tissue culture infective dose （TCID₅₀） was calculated after the cell cultures of each generation were collected ResultsEight fecal specimens were inoculated with Vero E6 cells after treatment and cultured for 48 h. One specimen showed obvious cytopathic effect on Vero E6 cells. One SARS-CoV-2 out of 8 fecal samples from COVID-19 patients were isolated， and separation rate was 12.5%. The TCID₅₀ of P1， P2 and P3 were 10^4.0/0.2 mL， 10^4.5/0.2 mL and 10^4.75/0.2 mL， respectively. Only one of the 8 stool samples had SARS-CoV-2 virus replication and amplification， and the Ct value of the nucleic acid detection was about 10. The sequence of the isolation was more than 99.99% homologous with that of Wuhan-Hu-1（GenBank MN908947）. ConclusionThe SARS-CoV-2 strain is isolated from the fecal samples of COVID-19 cases and is confirmed by genomic sequencing and immunofluorescence test， which indicates the presence of live virus in feces of COVID-19 cases.

Objective:To explore the etiologic characteristics of herpangina (HA) in Shanghai city, so as to provide scientific basis for HA control and prevention.Methods:Throat swabs of HA cases during 2017-2019 from sentinel hospital were collected. Fluorescent quantitative RT-PCR was conducted to detect nucleic acid of enterovirus (EV), EV-A71, coxsackievirus (CV)-A16, CV-A6 and CV-A10. Virus isolation was performed for the other EV-positive samples. The isolates were genotyped using semi-nested RT-PCR(RT-snPCR). The data were statistically analyzed with Excel and IBM SPSS Statistics 22.0.Results:A total of 264 HA cases were included, of whom 32.95%(87/264) were under 1 year of age, the human enteroviruses (HEVs)-positive rate was 69.70%(184/264), eight serotypes of EV including EV-A71, CV-A16, CV-A6, CV-Al0, CV-A4, CV-A2, CV-A5 and CV-B5 were detected. The CV-A6-positive rate was the highest with a percentage of 39.13%(72/184), followed by CV-A10 (17.39%, 32/184) and CV-A4 (16.85%, 31/184). From 2017 to 2019, the proportion of other EV increased year by year, which were 19.23% (10/52), 41.10% (30/73) and 47.46% (28/59), respectively.Conclusions:CV-A6, CV-A10 and CV-A4 were the main common pathogens of HA in Shanghai city during 2017-2019, and the proportion of other EV increased year by year.