OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.

Objective:To investigate the role of Pink1/Parkin-induced mitophagy in acute lung injury of exertional heat stroke rats.Methods:Sixty SD rats were randomly divided into four groups, including normal group (CON group), normal Parkin overexpression group (CON+Parkin group), heat stroke group (EHS group) and heat stroke Parkin overexpression group (EHS+Parkin group), with fifteen rats in each group. The rat model of exertional heat stroke was established and the survival curve was drawn. Pulmonary coefficient and pulmonary capillary permeability were detected. HE staining was used to observe the pathological changes of lung tissue. ELISA was used to detect the contents of IL-6, IL-1β, TNF-α and ROS in lung tissue; immunohistochemistry was used to observe apoptosis in lung tissue; Western blot was used to determine the expression of Pink1, Parkin, P62 and LC3 in rat lung tissue, and the LC3II/LC3I ratio was calculated. Single factor multi-level group comparison was performed by single factor analysis of variance, SNK-q method was used to further pairwise comparison between groups.Results:Compared with the normal group, the survival rate of EHS group was decreased ( P<0.001), lung coefficient and pulmonary vascular permeability were increased [(4.39±0.42), (33.38±8.29) μg/g, P<0.05)], lung tissue was exudative and solid, the levels of inflammatory factors IL-6, IL-1β, TNF-α and ROS were significantly increased[(34.31±5.34) pg/mL, (34.03±4.78) pg/mL, (91.64±8.16) pg/mL, (259.01±89.17) U/mg, P<0.05)], and apoptosis was increased. Western and immunohistochemistry results showed that the expressions of Pink1 and Parkin were decreased, co-location of Pink1and Parkin was attenuated, LC3II/LC3I were decreased, and P62 expression was increased. Compared with the EHS group, the survival rate of EHS+Parkin group was significantly increased ( P<0.05), lung coefficient and pulmonary vascular permeability were decreased [(3.83±0.62), (22.49±7.90) μg/g, P<0.05)], exudation and consolidation and other pathological changes were significantly reduced, and the levels of the above inflammatory factors and ROS were significantly decreased [(14.09±3.24) pg/mL, (26.94±2.11) pg/mL、(63.35±11.62) pg/mL, (161.13±26.31) U/mg, P<0.05]. Lung tissue apoptosis was reduced. The co-location of Pink1and Parkin、Parkin expression and LC3II/LC3I ratio were increased ( P<0.05), P62 expression was decreased( P<0.05), while Pink1 expression was not significant different (q=0.75). There was no difference between normal group and normal Parkin overexpression group (q=0.95). Conclusion:Activation of Pink1/Parkin-induced mitophagy can alleviate the acute lung injury in exertional heat stroke rats.

Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.

Objective:To analyze the impact of previous exposure to macrolide, quinolones and nitroimidazole antibiotics on eradication rate of bismuth quadruple therapy (BQT) in newly diagnosed patients with Helicobacter pylori( H. pylori). Methods:A total of 469 patients with H. pylori initially treated at the Third Hospital of Peking University from September 2017 to August 2020 were retrospectively recruited. The therapeutic regimens were BQT containing clarithromycin/levofloxacin/metronidazole recommended by Chinese guidelines. Clinical data were collected, including general demographic data, exposure history of antibiotics, CYP2C16 metabolic pattern, endoscopic diagnosis, bacterial density, H.pylori resistance, eradication results, etc. Univariate analysis, Chi-square test, Fisher exact probability test, Kruskal-Wallis H test and Logistic regression model were used as statistical methods. Results:Among different eradication therapies, univariate and multivariate analyses suggested that previous exposure to macrolides ( OR=3.37,95 %CI 1.04-10.98, P<0.05) was relevant to the decreased eradication rate of BQT containing clarithromycin. This may be due to increased resistance to clarithromycin ( OR=6.12,95 %CI 3.99-9.40, P<0.01).The previous exposure to quinolones ( OR=3.65, 95 %CI 1.27-10.49, P<0.05) was relevant to the decreased eradication rate of BQT containing levofloxacin, which was probably explained by the increased resistance to levofloxacin ( OR=2.50, 95 %CI 1.69-3.71, P<0.01). But the previous history of nitroimidazole did not impact the efficacy of BQT containing metronidazole. Conclusions:In patients newly diagnosed with H.pylori infection, the previous exposure to macrolide or quinolones antibiotics is related to lower eradiation rates of H. pylori. Although the exposure to nitroimidazole also indicates drug resistance to metronidazole, the clinical efficacy of BQT with metronidazole 400 mg four times a day is not affected.

We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.

Objective: To describe the epidemiological characteristics and clinical manifestations of the 2019 coronavirus disease (COVID-19) in pediatric patients, and to provide data support and decision-making basis for the prevention and control of COVID-19. Methods: Cases of children aged 0-17 years reported by provincial health commissions in Anhui, Shandong, Zhejiang and Henan provinces were collected to analyze their spatial, temporal, and demographic distribution. Results: By 24:00 on February 6, 2020, a total of 107 pediatric patients had been reported in the four provinces, accounting for 3.8% (107/2 808) of the total cases reported in the four provinces during the same period. Anhui, Shandong, Zhejiang and Henan provinces had 25, 25, 28 and 29 cases, respectively. Cases ranged in age from 5 days after birth to 17 years, with a median age of 8 years. Boys accounted for 58.9%. Totally 38 cases had a history of sojourn in Wuhan or Hubei, 63 cases had a history of exposure to confirmed cases, and 6 cases with unknown exposure history. A group of 52 family clustering were found in 107 cases. All cases presented mild symptoms, no serious and no death. Conclusion Children were also susceptible to the COVID-19. Before February 2, the index pediatric cases were mainly the first generation cases, and after February 3, these pediatric cases were mainly the secondary-generation cases and those who had close contact with confirmed cases. The monitoring of children with secondgeneration cases and close contact with COVID-19 cases were valued.

Objective To assess the efficacy of 308 nm excimer laser irradiation for the treatment of guinea pig model of vitiligo and its immunoregulatory effect on Treg cell and Th17 cell.Methods Vitiligo was induced in guinea pigs by hydroquinone bleaching,and they were randomly divided into an experimental group and a control group.There was also a normal control group.The experimental group was treated with a 308 nm excimer laser at the nidus of vitiligo; the two control groups were given no intervention.After 8 weeks of treatment,leukasmus of the different groups were compared.The mRNA expression of Foxp3 and IL-17 were measured by real-time fluorescence quantitative (RTFQ-PCR) and the expression of Foxp3 and IL-17 in the lesions were measured by immunohistochemistry staining.Results The effectiveness rate was 100％ in the experiment group.The results of RTFQ-PCR showed that the mRNA expression of Foxp3 in the experimental group and the vitiligo control group was significantly higher than the healthy control group (all P ＜ 0.05),being 0.33 ± 0.03 and 0.02 ±0.07 respectively,as was the mRNA expression of IL-17,being 0.21 ± 0.05 and 0.94 ± 0.06 accordingly; and the mRNA expression of IL-17 in the experimental group was significantly lower than the vitiligo control group(P ＜ 0.05).The immunohistochemical staining showed that Foxp3 and IL-17 protein was scattered in the lesions of the experimental group,while they were crowded in those of the vitiligo control group.Conclusion Laser irradiation might contribute to a therapeutic effect on vitiligo through modulating the balance of Treg and Th17 cells,at least in guinea pigs.

Adult ; Aged ; Female ; Humans ; Keratitis ; pathology ; Male ; Microscopy, Confocal ; methods ; Middle Aged ; Young Adult

BACKGROUNDHelicobacter pylori (Hp) is a common and potentially curable cause of gastric mucosa lesion. This study investigated the relationship of Hp infection with histological changes in gastric mucosa and gastric cancer in Hp-positive patients compared with Hp-eradication patients followed up for ten years.

METHODSFrom an initial group of 1 006 adults, 552 Hp-positive subjects were randomly assigned to a treatment group (T; n = 276) or a placebo group (P; n = 276). In the randomized, double-blind, placebo-controlled, parallel trial, T group subjects received oral doses of omeprazole, amoxicillin and clarithromycin for 1 week; those in the P group received a placebo. One month after treatment ended, a 13C urea breath test was performed, and Hp was undetectable in 88.89% of the T group. All subjects were followed at 1, 5, 8, and 10 years after treatment, with endoscopy and biopsies for histological examination.

RESULTSGastric mucosa inflammation was significantly milder in the T group than that in the P group one year after Hp eradication and this persisted for 10 years. Glandular atrophy and intestinal metaplasia (IM) had deteriorated in both groups during ten years. However, the increased score of glandular atrophy at both the gastric antrum and corpus, and IM only at the gastric antrum, in the P group was more obvious than that in the T group. During the 10 years, 9 patients were diagnosed with gastric cancer (2 in the T group; 7 in the P group; P = 0.176). When mucosal atrophy was absent at the gastric antrum and corpus when entering the study, the incidence of gastric cancer in the P group (n = 6) was much higher than that in the T group (n = 0, P = 0.013).

CONCLUSIONSHp eradication may significantly diminish and help halt progression of gastric mucosal inflammation and delay the development of IM and atrophy gastritis. Hp eradication is helpful for reducing the risk for gastric cancer, especially in the early stage of Hp infection.

Adult ; Aged ; Amoxicillin ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Clarithromycin ; therapeutic use ; Double-Blind Method ; Female ; Follow-Up Studies ; Gastric Mucosa ; drug effects ; pathology ; Gastritis, Atrophic ; diagnosis ; drug therapy ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; pathogenicity ; Humans ; Male ; Middle Aged ; Omeprazole ; therapeutic use ; Stomach Neoplasms ; diagnosis ; prevention & control

Objective To evaluate the efficacy and safety of fractionated CO2 laser combined with 308-nm excimer laser for the treatment of stable vitiligo.Methods Forty-nine patients with 109 lesions of stable vitiligo were enrolled in this clinical trial.Each of these lesions was equally divided into 2 parts along the longest diameter,which were then assigned into the treatment group and control group respectively.The treatment group were treated with fractionated CO2 laser radiation for 15-20 minutes once every two weeks combined with 308-nm excimer laser radiation twice weekly.The control group were only treated with 308-nm excimer laser radiation twice weekly.Efficacy was evaluated on day 3 after 12 consecutive weeks of treatment.Results After the treatment,the total response rate in the treatment group and control group was 92.7％ (101/109) and 77.1％ (84/109) respectively.The marked response rate in the treatment group and control group was 85.4％ (35/41) and 65.8％ (27/41) respectively for lesions on the face and neck (x2 =4.23,P ＜ 0.05),70.6％ (24/34) and 41.2％ (14/34) respectively for lesions on the trunk (x2 =7.27,P＜ 0.01),64.0％ (16/25) and 36.0％ (9/25) respectively for lesions on the extremities (x2 =3.92,P ＜ 0.05),5/9 and 1/9 respectively for lesions on the dorsal hands (X2 =4.00,P ＜ 0.05).The number of sessions of 308-nm excimer laser therapy required for the marked response of vitiligo in the treatment group and control group was 7.24 ± 1.23 and 10.81 ± 2.01 respectively for lesions on the face and neck (t =9.70,P ＜ 0.05),15.10 ± 2.47 and 18.95 ± 3.45 respectively for lesions on the trunk (t =5.29,P＜ 0.05),17.37 ± 3.84 and 21.06 ± 4.23 respectively for lesions on the extremities (t =3.23,P ＜ 0.05).No severe adverse reactions were observed in any of the patients during the treatment.Conclusion Fractionated CO2 laser combined with 308-nm excimer laser is effective and safe in treating stable vitiligo.