Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

OBJECTIVE To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-β induced LX-2 cell fibrosis. METHODS Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL−1).The effects on cell proliferation were detected by CCK-8. The effects on cell apoptosis was detected by flow cytometry. The effects on fibrosis related factors(Collagen I, Collagen Ⅳ, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, MMP2, MMP9, TIMP1 and TIMP2) protein expression and gene transcription levels were detected by Western blotting and q-PCR. RESULTS The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells, and the IC25 values were 15.7, 2.6, 10.2 μmol·L−1, respectively. Compared to the model group, the curcumin(15.7 μmol·L−1) and its derivative A(2.6 μmol·L−1) and B(10.2 μmol·L−1) had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P<0.05). The cell apoptosis rate of curcumin derivative B group was higher than the model group(P<0.05). Collagen I, Fibronectin, Vimentin, α-SMA, TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower, while the protein expression level of MMP-9 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, TIMP-1 and TIMP-2 in curcumin derivative A group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, TIMP-1 and TIMP-2 in curcumin derivative B group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The gene transcription levels of Collagen I, Fibronectin, α-SMA and TIMP-1 in curcumin group were lower(P<0.05). The gene transcription levels of Collagen I, Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P<0.05). CONCLUSION Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells, inhibit the excessive secretion and accumulation of its extracellular matrix components, and promote its degradation, thus playing an anti-fibrotic effect in vitro, especially the curcumin derivative B.

Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.

Objective:To investigate the clinicopathological features and molecular characteristics of β-catenin-deficient colorectal cancer.Methods:The clinical, pathological and molecular features of 11 colorectal cancers with β-catenin protein loss diagnosed at the 960th Hospital of People′s Liberation Army of China, from January 2012 to November 2022 were analyzed.Results:Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. β-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of β-catenin protein expression.Conclusion:β-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

Objective:To obsere the clinical efficacy of Hall technology in the treatment of primary molar caries in children with au-tism.Methods:80 children aged 4-8 years with primary molar caries,40 normal children and 40 children with autism,with a total of 153 primary molars.The normal and the autism children were respectively divided into 2 groups(n=20)randomly.The normal children were grouped into resin filling(CR)of 38 teeth and Hall technology group(CH)of 39 teeth,the autistic children were grouped into resin filling(AR)of 37 teeth and Hall technology group(AH)of 38 teeth.Corresponding treatment was given to the pa-tients in the groups.The duration of oral treatment time,Frankl scores,Houpt scores and parental satisfaction scoves were compaired among groups.The patients were followed up for 6,12,18 and 24 months and the treatment outcomes were compared among groups.Results:There was no statistically difference between CH group and AH group in terms of operating time,compliance,Houpt score and follow-up effects(P＞0.05).The satisfaction of parents in the AR group was the lowest(P＜0.05).Hall technology treatment re-mained effective rate was higher than resin filling at the 24 month follow-up(P＜0.05).Conclusion:Hall technology is more effective than traditional resin filling in the treatment of primary molars caries in children with autism.

Objective:To investigate the clinicopathological characteristics of dedifferentiated endometrial carcinoma/undifferentiated endometrial carcinoma (DDEC/UDEC) with loss of expression of SMARCA4.Methods:A total of 10 cases with loss of expression of SMARCA4 were diagnosed at Fujian Cancer Hospital between January 2019 and December 2023. A retrospective analysis was conducted on the clinical characteristics, morphology, immunophenotype, molecular classification, and prognosis.Results:(1) Clinical characteristics: among 10 cases of DDEC/UDEC with loss of expression of SMARCA4, the patients′ age ranged from 48 to 65 years, with a median age of 56 years.Five cases were classified as International Federation of Gynecology and Obstetrics (FIGO) stages Ⅰ-Ⅱ, while the remaining five were categorized as stages Ⅲ-Ⅳ. (2) Pathological features: tumor cells exhibited poor cell adhesion, with common intravascular tumor emboli (8/10), occasional vacuolated nuclei (6/10), rhabdoid cells (4/10), and starry sky phenomenon formed by tissue cell phagocytosis apoptosis bodies or fragments (4/10). Six cases (6/10) showed loss of mismatch repair (MMR) protein expression, two cases (2/10) exhibited p53 mutant expression, and five cases (5/10) tested positive for programmed cell death ligand 1 (PD-L1). (3) Molecular subtyping: molecular subtyping revealed POLEmut in 1 case (1/10), mismatch repair deficient (MMR-d) in 5 cases (5/10), p53 abn in 1 case (1/10), and no specific molecular profile (NSMP) in 3 cases (3/10). (4) Prognosis: the follow-up period ranged from 7 to 42 months, with a median of 20 months. Five patients succumbed to the tumor, whereas the remaining five exhibited no recurrence during subsequent postoperative evaluations. The 2-year progression-free survival rates and overall survival rates were 58.3% and 52.5%, respectively.Conclusions:Loss of expression of SMARCA4 occurs in approximately 1/5 of DDEC/UDEC, which presents with an aggressive clinical course and a poor prognosis. About half of them show MMR protein loss expression and PD-L1 positive expression, suggesting that there might be benefit from treatment with immune checkpoint inhibitors.

Objective:To explore the risk factors affecting endometrial lesions after breast cancer surgery, and build a nomogram prediction model.Methods:From Oct. 2019 to Nov. 2021, 103 patients with abnormal bleeding after breast cancer surgery were selected, the clinical data of the patients were collected, and they were divided into the non-lesion group and the lesion group according to whether the endometrial lesion occurred. A Logistic risk regression model was established to analyze the risk factors affecting endometrial lesions in postoperative patients with breast cancer, a nomogram prediction model was constructed and verified, and receiver operating characteristic curve (ROC) analysis was performed to analyze the nomogram model for predicting sensitivityof endometrial lesions.Results:Childbirth history ( OR=37.100, 95% CI: 3.777-527.7, P=0.004), endometrial thickness ( OR=2.489, 95% CI: 1.699-4.007, P<0.001), menopause ( OR=0.099, 95% CI: 0.015-0.499, P=0.009), abnormal bleeding time ( OR=6.922, 95% CI: 2.221-24.800, P=0.002), and types of treatment drugs ( OR=3.738, 95% CI: 1.187-13.200, P=0.030) had statistical significance in predicting endometrial lesions in postoperative patients with breast cancer. Using the above five variables to construct a nomogram model, the consistency of the nomogram in predicting endometrial lesions in postoperative patients with breast cancer was 0.739, and the discrimination was good. The calibration curve showed that the average absolute error between the predicted probability and the actual probability was 0.041,and ROC curve showed that the AUC value of the nomogram model for predicting endometrial lesions was 0.800. Conclusion:Establishing a nomogram model for predicting the risk of endometrial lesions in postoperative patients with breast cancer has good accuracy and high clinical value.

Objective:To investigate the changes of ROS/TXNIP/NLRP3 signaling pathway in pyroptosis of human embryonic trophoblast cells induced by high glucose.Methods:Human embryonic trophoblast cells were cultured in vitro to establish high glucose injury model, and they were randomly divided into control group, high glucose (HG) group and HG + ROS inhibitor N-acetyl-L-cysteine (HG + NAC) group. MTT assay was used to detect the cell survival rate. The level of ROS in each group was detected by dihydroethidine ROS fluorescence probe. Expression of TXNIP and NLRP3 mRNA was detected by real-time quantitative PCR (RT-qPCR). Western blot analysis was used to detect the expression levels of TXNIP, NLRP3, Caspase-1, interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) and GSDMD proteins. In addition, pyroptosis was detected by flow cytometry.Results:The optimal glucose concentration for high glucose-induced injury of human embryonic trophoblast cells was 30 mmol/L. Compared with the control group (96.27±3.10) %, the survival rate of human embryonic trophoblast cells in HG group (55.44±2.15) % was significantly lower ( P<0.05), while the fluorescence intensity (ROS level) of 7 'dichlorofluorescein (DCF), the expression levels of TXNIP and NLRP3 proteins, the number of pyroptosis, expression levels of Caspase-1, GSDMD, IL-1β and TNF-α proteins were significantly higher ( P<0.05) ; Compared with HG group, the survival rate of human embryonic trophoblast cells in HG+NAC group (84.75±2.33) % was significantly higher ( P<0.05), the fluorescence intensity (ROS level) of DCF, the expression levels of TXNIP and NLRP3 proteins, the number of pyroptosis, and expression levels of Caspase-1, GSDMD, IL-1β and TNF-α proteins were significantly lower ( P<0.05) . Conclusion:Inhibition of ROS level in human embryonic trophoblast cells induced by high glucose may promote cell proliferation and reduce the occurrence of pyroptosis by inhibiting TXNIP/NLRP3 signaling pathway.

ObjectiveTo compare the incidence of respiratory and allergic diseases in children in Xuhui District， Shanghai in 2013 and 2020， and to determine the influencing factors. MethodsAnnual average levels of air pollutants including PM_2.5， PM₁₀， O₃， SO₂， and NO₂ were collected and described in Shanghai from 2013 to 2020. A cross-sectional survey was conducted by using a questionnaire among grade 3 to 5 students in a school in Xuhui District， Shanghai， in September 2013 and 2020， respectively. The questionnaire collected variables including living environment， daily habits， family history of respiratory and allergic diseases， and incidence of these diseases in children. Chi-square test was used to determine the difference across respiratory and allergic diseases. Logistic regression was conducted to determine the influencing factors. ResultsA total of 1 398 valid questionnaires were collected （705 in 2013 and 693 in 2020）. Compared with 2013， annual average concentrations of PM_2.5， PM₁₀， O₃， SO₂， and NO₂ in 2020 significantly decreased. The prevalence of bronchial asthma， bronchitis， persistent cough and persistent expectoration in 2013 were significantly higher than those in 2020 （P<0.05） in Xuhui District. Multivariate analysis showed that severe air pollution， boys， parents with asthma or allergy， parents with higher educational levels， and more allergens in household were the risk factors associated with the incidence of bronchial asthma， bronchitis， allergic rhinitis and atopic eczema （P<0.05）. Parents with allergy history， high smoking frequency of family member， and more allergens in household were the risk factors associated with the incidence of persistent cough and persistent expectoration （P<0.05）. ConclusionTo 2013，2020 air pollution in Shanghai has been mitigated and prevalence of bronchial asthma and bronchitis of children has decreased. Childhood respiratory and allergic diseases are associated with indoor and outdoor environment， family medical history， and family daily habits.

Abstract OBJECTIVE To study the mechanism of NLRP3 gene’s regulation on inflammatory response in non-alcoholic fatty liver disease(NAFLD) mice induced by high-fat and high-fructose diet using NLRP3 gene knockout mice. METHODS Use male homozygous(NLRP3-/-) mice, and the high-fat and high-fructose diet was used to establish NAFLD model in NLRP3 knockout(KO) mice and wild-type(WT) mice, divided into KO high-fat and high-fructose diet(KO-HFD) group and WT high-fat and high-fructose diet(WT-HFD) group, while the WT and KO groups were also established. The body weight of mice in each group were observed. The changes of ALT, AST, TG, TC, MDA, SOD, lipidosis, apoptosis rate, IL-1β, IL-18, TNF-α, NF-κB, NLRP3, Caspase-1 and ASC in serum and tissue samples were tested to study the mechanism of the NLRP3 gene regulating the inflammatory response in NAFLD mice. RESULTS As time goes on, the mice weight of each group increased gradually, but the KO-HFD group increased less than the WT-HFD group. Each group’s level of ALT, AST, TG, TC in serum increased gradually, but the KO-HFD group increased less than the WT-HFD group. The level of MDA in liver tissues of each group was gradually increased and the level of SOD was gradually decreased, but the change range of KO-HFD group was smaller than that of WT-HFD group. The results of oil red O staining and Tunel section showed that the degree of lipid deposition and apoptosis in hepatocytes increased gradually in all groups, but the changes in KO-HFD group were less than that in WT-HFD group. The levels of serum and liver inflammatory factors IL-1β, IL-18, TNF-α and NF-κB increased in all groups, but the changes of KO-HFD group 20 weeks were less than those of WT-HFD group 20 weeks, and the difference was statistically significant. The expression levels of NLRP3 inflammasomes and related inflammatory cytokines NLRP3, Caspase-1, ASC, IL-1β and IL-18 in liver tissues of WT-HFD group were higher than those of KO-HFD group. The mRNA transcription levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in WT-HFD group were gradually increased, while there was no change in KO-HFD group. CONCLUSION The NLRP3 gene may be activated in NAFLD mice model, resulting in increased expression of NLRP3 inflammasome-associated protein, promoting the synthesis and secretion of downstream inflammatory factors, resulting in significant inflammatory response and liver damage, and promoting the progression of NAFLD disease.