To assess the protective effects of luteolin(LT)on liver fibrosis in rats with autoimmune hepatitis(AIH)and to explore the underlying mechanisms,total of 62 rats were recruited and randomly divided into normal control group(CT),AIH model group(AIH),LT low-dose group(LT L),LT medium-dose group(LT M),LT high-dose group(LT H)and prednisolone group(PSL),with 10 rats in each group.The rat in CT group were injected with an equivalent volume of physiological saline via the tail vein,when the rat in the other groups were received tail vein injection of concanavalin A(Con A)dissolved in physiological saline to induce the AIH model.Then,the rat in LT L,M,and H groups were administered intraperitoneal injections of LT dissolved in physiological saline(at doses of 5,25,and 50 mg/kg,respectively),and the rat in the PSL group received intraperitoneal injections of PSL dissolved in physiological saline(at a dose of 10.0 mg/kg),while the rat in the CT and AIH groups received equivalent volumes of physiological saline intraperitoneally.All treatments were administered twice daily for 7 consecutive days.The day after the last treatment,liver function indices,peripheral blood lymphocyte subsets,and hepatic hydroxyproline content were measured.Furthermore,Masson staining was used to assess the liver fibrosis was assessed using,and Western blot analysis was performed to detect the expression levels of activated nuclear factor κB(NF-κB),phosphorylated NF-κB(p-NF-κB),inhibitor of nuclear factor κBα(IκBα),and phosphorylated IκBα(p-IκBα)proteins in liver tissue.Compared to the CT group,the AIH group exhibited significantly higher serum levels of alanine aminotransferase(ALT),total bilirubin(TBIL),CD4+T lymphocyte ratio,CD4+/CD8+ratio,and hepatic hydroxyproline content(P<0.05),while albumin(ALB)levels and the CD8+T lymphocyte ratio were significantly lower(P<0.05).LT in all doses could reverse these changes mentioned above in AIH rats in a dose-dependent manner(P<0.05),and no significant differences were observed between the LT H group and the PSL group in these parameters(P>0.05).Masson staining results revealed that liver fibrosis in the LT groups was less severe than that in the AIH group,with a clear dose-dependent effect.The PSL group exhibited similar antifibrotic effects to the LT H group.Furthermore,the AIH group showed significantly higher levels of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios in liver tissue,as compared to the CT group(P<0.05),while LT could suppress the increase of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios(P<0.05)in a dose-dependent manner(P<0.05),and no significant differences in these ratios were observed between the LT H group and the PSL group(P>0.05).Taken together,Luteolin can improve liver function and immune function,and alleviate liver fibrosis by inhibiting the NF-κB pathway in AIH rats.

Nipah virus (NiV) is a highly contagious zoonotic pathogen, responsible for a relatively high mortality in human and posing a serious threat to human health. There are currently no licensed vaccines or antiviral drugs. Preclinical studies on NiV vaccines with different strategies are mainly based on NiV glycoprotein (G) and/or fusion protein (F). Internationally, three NiV vaccine candidates are currently in the Phase I clinical stage. The risk of Nipah virus transmitted to China is relatively high. In order to cope with potential future epidemics, China should develop NiV prevention and control strategies, and accelerate Nipah virus-related technology reserves and vaccine development. This article introduces NiV from the aspects of microbiology, epidemiology, clinical characteristics, and vaccine research, and puts forward prevention and control suggestions in light of the risk of NiV transmission to China and China′s national conditions, hoping to provide reference for NiV vaccine research and development.

Drought is a common limiting factor affecting rice yield and quality. Cerium oxide nanoparticles(nanoceria) have been widely reported to improve crop stress tolerance. However, the effects and mechanisms of nanoceria on rice drought tolerance are still unknown. The aim of this study is to investigate whether nanoceria can improve rice drought tolerance by modulating reactive oxygen species(ROS) homeostasis and nitric oxide(NO) levels. Our results showed that compared with no-nanoparticle treatment, nanoceria significantly increased the fresh weight of rice seedlings under drought stress(19%, P < 0. 05). Also, under drought stress, the ROS level of rice leaves treated with nanoceria was significantly lower(82%, P < 0. 05) than leaves treated with buffer. The leaf NO level after nanoceria treatment, however, is significantly higher(46%, P < 0. 05) than that with no-nanoparticle treatment under drought stress. Moreover, compared with control plants, nanoceria maintained better membrane integrity in rice leaf cells under drought stress, showing a 70% decrease(P < 0. 05) in dead leaf cells. This study explores the mechanisms underlying nanoceria’s improved rice drought tolerance by affecting ROS and NO levels, which not only further enriches our knowledge about the interaction between nanoparticles and crops under abiotic stress but also gives more support on the sustainable development of nano-enabled agriculture.

AIM:To observe the clinical effect of different concentration of fluorometholone eye drops on severe mixed vernal keratoconjunctivitis in children.METHODS: A total of 50 cases(100 eyes)of children with severe mixed vernal keratoconjunctivitis treated in the outpatient department of our hospital from March to September, 2022 were selected and randomly divided into two groups. Group A consisted of 25 cases(50 eyes)who were treated with 0.1% fluorometholone eye drops combined with 0.05% cyclosporine eye drops(Ⅱ), while 25 patients(50 eyes)in group B were treated with 0.02% fluorometholone eye drops combined with 0.05% cyclosporine eye drops(Ⅱ). After 1mo of treatment, SPEED questionnaire score, corneal fluorescein staining(FL)score, tear break-up time(TBUT), Schirmer I test(SⅠt), R-scan, non-invasive tear meniscus height(NIKTMH), corneal optical density and other ocular parameters of the two groups were observed, and the occurrence of adverse reactions were recorded.RESULTS: After 1mo of treatment, there were significant differences in SPEED score, FL score and R-scan results between the two groups(all P<0.05), and no differences in TBUT, SⅠt and NIKTMH results(all P>0.05). However, there were statistical significance in corneal optical density in different corneal depth and diameter ranges(all P<0.05). After 1mo of treatment, there was no significant difference in intraocular pressure between the two groups(16.21±2.90mmHg vs. 16.05±2.75mmHg, P>0.05), and no obvious adverse reactions occurred during treatment.CONCLUSION: The 0.1% fluorometholone eye drops can effectively treat severe mixed vernal keratoconjunctivitis in children, and its effect is better than 0.02% fluorometholone eye drops.

Objective:To analyze the different clinicopathological features of intrahepatic cholangiocarcinoma with and without viral hepatitis.Methods:The clinicopathological data of 79 intrahepatic cholangiocarcinoma cases from Mar 2012 to Sep 2018 at Henan Provincial People's Hospital were retrospectively analyzed.Results:Twenty-five of the 79 patients with intrahepatic cholangiocarcinoma were accompanied by viral hepatitis. Those with viral hepatitis had a lower mean age at onset than those without [(53±11) years vs. (60±11) years, P=0.011], higher proportion of male patients (80% vs. 52%, P=0.017), higher AFP positive rate (40% vs. 19%, P=0.041), lower CA19-9 positive rate (48% vs. 72%, P=0.036), tend to occur in the right liver lobe (76% vs. 44%, P=0.009), a lower rate of bile duct invasion (16% vs. 41%, P=0.03), and were more likely to be mass type (mass type proportion 96% vs. 72%, P=0.032). Conclusions:Viral hepatitis is common in intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma with and without viral hepatitis differ in clinicopathology. Intrahepatic cholangiocarcinoma with viral hepatitis is more likely to have the characteristics of hepatocellular carcinoma, while intrahepatic cholangiocarcinoma without viral hepatitis is more likely to have the characteristics of cholangiocarcinoma.

Genome-wide association studies (GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts (OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability, suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line (HIOEC) using RNA-seq, ATAC-seq, H3K27ac ChIP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only (NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification pipeline. In total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epithelium-expressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.
Chromatin ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Epithelium ; Genome-Wide Association Study ; Humans

Objective To establish early forecasting model of tuberculosis in schools of Hongshan district, and provide scientific strategy for prevention and control of tuberculosis. Methods Using data on 2013-2020 in schools tuberculosis, established time series models and chosen the best one to forecast and tested the incidence of tuberculosis. Results The best model for school tuberculosis was ARIMA (0,0,3) (0,1,1)₁₂. The trend of the predicted value was basically consistent with the actual value which was also in the 95% confidence interval of predicted numbers. The effectiveness of forecasting was good with a 2.313% value of MAPE. Conclusion The ARIMA product seasonal model can effectively fit and forecast time series data on students'’ tuberculosis. It also can be used to early warn and predict the incidence of school tuberculosis in Hongshan district.

Objective:To compare the difference of the ocular surface and efficacy of orthokeratology lenses wearing after using sodium hyaluronate eye drops, rewetting drops and saline solution.Methods:A randomized single-blind controlled trial was conducted.A total of 90 right eyes from 90 myopic patients were recruited from June 2017 to April 2018 in Hainan Eye Hospital.All the subjects received vision correction by orthokeratology lens, and were randomly divided into three groups by random number table method, with 30 eyes in each group.The sodium hyaluronate group was given preservative-free sodium hyaluronate eye drops (1 g/L), the rewetting drops group was given rewetting drops, and the saline solution group was given nonpreserved 0.9% NaCl.The vision, subjective refraction, corneal topography, non-invasive first tear film break-up time(NIKf-BUT) and fluorescein stain of corneal epithelium (FL) were detected before and 1 day, 1 week, 1 month, 3 months after the lens wearing.This study adhered to the Declaration of Helsinki and was approved by the institutional Ethical Committee Review Board of Hainan Eye Hospital.Results:The NIKf-BUT in the sodium hyaluronate group at 1 day, 1 week, 1 month and 3 months after wearing orthokeratology lens was (7.13±1.71), (6.61±1.49), (6.37±1.82) and (7.01±1.63) seconds, respectively, which was obviously higher than (6.32±1.71), (5.53±1.42), (5.57±1.50) and (6.17±1.63) seconds in the rewetting drops group at the corresponding time points and (6.36±1.58), (5.81±1.49), (5.74±1.77) and (6.28±1.53) seconds in the saline solution group at the corresponding time points (all at P<0.05). There was no statistically significant difference in FL score between the rewetting drops group and saline solution group at 1 day, 1 week, 1 month and 3 months after wearing the orthokeratology lens (all at P>0.05). Lower FL scores were observed in the sodium hyaluronate group compared to the the rewetting drops group and saline solution group after wearing the orthokeratology lens (all at P<0.05). No differences were found in uncorrected visual acuity, spherical equivalent and average K value among the groups (all at P>0.05). Conclusions:Compared with the rewetting drops and saline solution, the preservative-free sodium hyaluronate eye drops can stabilize the tear film and have less effect on corneal epithelium at the early stage of orthokeratology lens wearing.However, there is no significant difference in the improvement of visual acuity and the rate of corneal shaping.

Objective:To investigate the in vitro interaction between antifungals and tacrolimus against Fusarium solani. Methods:According to Clinical and Laboratory Standards Institute(CLSI) M27-Ed4 and M38-A3, 24 strains of Fusarium solani isolated from clinic were used to test the minimal inhibitory concentration (MIC) of the four antifungals.Chessboard microdilution method was used to evaluate the interaction of tacrolimus (FK506) combined with four antifungals in vitro.The study protocol was approved by the Ethics Committee of Hainan Eye Hospital (No.2017-006). Results:The MIC ranges of fluconazole, voriconazole, natamycin and amphotericin B against 24 strains of Fusarium were 64-256 μg/ml, 1-8 μg/ml, 2-8 μg/ml and 1-8 μg/ml, respectively.Tacrolimus combined with fluconazole, voriconazole, natamycin and amphotericin B had synergistic effects on 12.5% (3/24), 4.2% (1/24), 16.7% (4/24) and 29.2% (7/24) Fusarium, respectively.There were no antagonistic effect in this study. Conclusions:Fusarium is sensitive to natamycin in vitro and partly sensitive to amphotericin B and voriconazole.Synergistic effects exist in few strains of Fusarium but no antagonistic effect.

Objective To investigate the prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis.Methods The retrospective case-control study was conducted.The clinicopathological data of 995 patients with stage Ⅲ gastric cancer who were admitted to the Zhongshan Hospital of Fudan University between January 2003 and December 2014 were collected.There were 690 males and 305 females,aged from 20 to 75 years,with an average age of 61 years.After clinical staging according to results of preoperative accessory examinations,patients with early gastric cancer underwent D1+ lymphadenectomy,patients with advanced gastric cancer underwent D2 lymphadenectomy and patients with serosa invasion underwent D2+ lymphadenectomy.Observation indicators:(1) treatment situations;(2) follow-up and survival situations;(3) prognostic factors analysis after operation;(4) stratified analysis:① stratified analysis of tumor pathological N staging;② stratified analysis of number of lymph node dissected;③ stratified analysis of tumor pathological TNM staging;(5) receiver operating characteristic (ROC) curve.Patients were followed up using outpatient examination and telephone interview to detect postoperative survival up to January 2016.The overall survival time was from the operation data to last follow-up or time of death.Measurement data with normal distribution were represented as Mean±SD.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method and Log-rank test was used for survival analysis.The COX proportional hazard model was used for univariate and multivariate analysis.The ROC curve and area under curve (AUC) were used to check the accuracy of number of positive lymph nodes and metastatic lymph node ratio for prognosis.Comparison of the AUC was analyzed by the Z test.Results (1) Treatment situations:of 995 patients underging gastrectomy,677 underwent distal gastrectomy,85 underwent proximal gastrectomy,233 underwent total gastrectomy.There were 117 undergoing D1+ lymphadenectomy and 878 undergoing D2 lymphadenectomy or D2+ lymphadenectomy.The number of lymph node dissected,number of positive lymph nodes,metastatic lymph node ratio were 27± 12,10± 9 and 0.41±0.28,respectively.(2) Follow-up and survival situations:995 patients were followed up for (35± 32)months.During the follow-up,the 1-,3-,5-year overall survival rates were 77.9％,47.8％,36.2％.(3) Prognostic factors analysis after operation:results of univariate analysis showed that sex,tumor histological type,vascular embolus,degree of tumor invasion,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were related factors affecting prognosis of radical gastrectomy for stage Ⅲ gasteric cancer (hazard ratio =0.817,1.486,1.268,2.173,1.957,1.737,3.357,2.169,95％ confidence interval:0.686-0.973,1.059-2.086,1.074-1.497,1.195-3.954,1.480-2.588,1.390-2.170,2.476-4.602,1.740-2.704,P＜0.05).Results of multivariate analysis showed that sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer (hazard ratio =0.805,1.476,0.237,1.475,3.811,3.600,95％ confidence interval:0.673-0.963,1.049-2.087,0.083-0.678,1.140-1.909,2.259-6.428,1.317-9.839,P＜0.05).(4) Stratified analysis:of the 995 patients,the postoperative l-,3-,5-year overall survival rates were 93.7％,69.6％,60.5％ in the patients with metastatic lymph node ratio ≤ 0.1,86.9％,60.6％,44.3％ in the patients with 0.1 ＜ metastatic lymph node ratio ≤0.4 and 64.3％,28.9％,21.0％ in the patients with metastatic lymph node ratio ＞ 0.4,showing a statistically significant difference (x2 =121.300,P＜0.05).There were statistically significant differences between patients with metastatic lymph node ratio ≤0.1 and patients with 0.1＜ metastatic lymph node ratio ≤0.4,between patients with metastatic lymph node ratio ≤0.1 and patients with metastatic lymph node ratio ＞0.4 (x2=7.580,65.320,P＜0.05).There was a statistically significant difference between patients with 0.1 ＜ metastatic lymph node ratio ≤0.4 and patients with metastatic lymph node ratio＞0.4 (x2 =80.806,P＜0.05).① Stratified analysis of tumor pathological N staging:the average metastatic lymph node ratio was 0.09 in the 132 stage N1 patients,who were divided into the patients with metastatic lymph node ratio ≤ 0.1 and ＞ 0.1.The postoperative 1-,3-,5-year overall survival rates were 92.2％,68.6％,59.1％ in the 108 patients with metastatic lymph node ratio ≤ 0.1 and 79.2％,32.8％,21.9％ in the 24 patients with metastatic lymph node ratio ＞0.1,respectively,showing a statistically significant difference (x2 =14.499,P＜0.05).The average metastatic lymph node ratio was 0.23 in the 265 stage N2 patients,who were divided into the patients with metastatic lymph node ratio ≤0.2 and ＞0.2.The postoperative 1-,3-,5-year overall survival rates were 92.3％,73.8％,61.0％ in the 138 patients with metastatic lymph node ratio ≤0.2 and 76.5％,40.1％,22.2％ in the 127 patients with metastatic lymph node ratio ＞0.2,respectively,showing a statistically significant difference (x2 =42.536,P＜0.05).The average metastatic lymph node ratio was 0.56 in the 598 stage N3 patients,who were divided into the patients with metastatic lymph node ratio ≤0.4 and ＞0.4.The postoperative 1-,3-,5-year overall survival rates were 88.5％,62.8％,47.0％ in the 194 patients with metastatic lymph node ratio ≤ 0.4 and 64.3％,29.8％,21.0％ in the 404 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2 =51.860,P＜ 0.05).② Stratified analysis of number of lymph node dissected:7 of 117 patients with the number of lymph node dissected ＜ 15 had metastatic lymph node ratio ≤0.1,who were divided into patients with metastatic lymph node ratio ≤0.4 and ＞0.4.The postoperative 1-,3-,5-year overall survival rates were 78.2％,40.0％,28.6％ in the 44 patients with metastatic lymph node ratio ≤0.4 and 78.1％,18.7％,12.9％ in the 73 patients with metastatic lymph node ratio＞0.4,respectively,showing a statistically significant difference (x2 =4.727,P＜0.05).③ Stratified analysis of tumor pathological TNM staging:of 262 patients with stage Ⅲa gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 88.5％,65.0％,54.3％ in the 230 patients with metastatic lymph node ratio ≤0.4 and 77.5％,35.4％,29.5％ in the 32 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2 =6.132,P＜0.05).Of 296 patients with stage Ⅲb gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.4％,60.7％,42.7％ in the 200 patients with metastatic lymph node ratio ≤ 0.4 and 59.9％,26.8％,21.7％ in the 96 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2 =23.699,P＜0.05).Of 437 patients with stage Ⅲ c gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.7％,59.9％,38.7％ in the 133 patients with metastatic lymph node ratio ≤0.4 and 64.0％,27.9％,18.3％ in the 304 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2=36.215,P＜ 0.05).(5) ROC curve:ROC curves of postoperative overall survival rates in patients with stage Ⅲ gastric cancer were drawn using the number of positive lymph nodes and metastatic lymph node ratio,of which AUC were 0.619 (95％ confidence interval:O.588-0.649) and 0.706 (95％ confidence interval:0.677-0.734),showing a statistically significant difference (Z=8.842,P＜0.05).Conclusions Sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging are independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer.There is different prognosis of patients with different metastatic lymph node ratios in the subgroup of the same tumor pathological TNM staging,number of lymph node dissected,tumor pathological TNM staging.Compared with tumor pathological N staging,metastatic lymph node ratio has a more accurate predictive value for prognosis.