Objective: To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients. Methods: Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models. Results: A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to <45 years (1 664 cases, 39.49%). The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were 36.81%, 30.21% and 38.09%, respectively. Delay in healthcare-seeking was associated with the year (2018, OR=0.708; 2019, OR=0.549; 2020, OR=0.670; 2021, OR=0.682), gender (female, OR=1.199), occupation (worker, OR=1.379; housekeeping service/housework/unemployed, OR=1.481), case identification route (symptom-based consultation, OR=11.159), and level of the first-diagnosed hospital (city-level, OR=1.528). Delay in definitive diagnosis was associated with age (45 to <65 years, OR=1.476), occupation (commercial service, OR=0.687; housekeeping service/housework/unemployed, OR=0.672), household registration (non-local, OR=0.820), case identification route (symptom-based consultation, OR=0.616), pathogen test result (negative/not tested, OR=1.903), and the level of the first-diagnosed hospital (city-level, OR=0.311). Delay in identification was associated with the year (2018, OR=0.785; 2019, OR=0.647; 2020, OR=0.790; 2021, OR=0.710), occupation (commercial service, OR=0.687), household registration (non-local, OR=0.848) and level of the first-diagnosed hospital (city-level, OR=0.560) Conclusions Year, gender, occupation, case identification route and level of the first-diagnosed hospital are influencing factors for delay in healthcare-seeking in PTB patients. Age, occupation, household registration, case identification route, pathogen test result and level of the first-diagnosed hospital are influencing factors for delay in definitive diagnosis. Year, occupation, household registration and level of the first-diagnosed hospital are influencing factors for delay in identification.

OBJECTIVE To explore the levels of helper T lymphocytes(Th)in patients with hepatitis B virus(HBV)infection who were treated with entecavir and observe the impact on viral clearance.METHODS A total of 149 patients with HBV infection who were treated with entecavir in Yan'an Hospital of Kunming City from Jan.2020 to Jan.2024 were enrolled in the study,82 of whom were chronic hepatitis B(CHB),and 67 were chro-nic hepatitis B virus carriers.The enrolled patients were divided into the clearance group with 64 cases and the no clearance group with 85 cases according to the levels of serum hepatitis B surface antigen(HBsAg)at Week 72 of the treatment.The clinical data were compared between the two groups,and the changes of Th1 and Th2 levels during the treatment were analyzed.Multivariate linear regression analysis was performed for the association be-tween virological change during the treatment and immune level.The risk factors for failed clearance of viruses were analyzed by logistic regression model.RESULTS There were significant differences in the age,the levels of alanine aminotransferase(ALT)and HBV DNA between the baseline and Week 24,the levels of aspartate trans-aminase(AST)at the baseline and Week 12,the HBsAg level at Week 24,and the baseline levels of Th1,Th1/Th2 between the CHBc treatment group and the CHB treatment group(P＜0.05).There were linear correlations between the HBV DNA,HBsAg,hepatitis E antigen(HBeAg)and the Th1,Th2 and Th1/Th2,respectively(P＜0.05).Totally 64 patients were accumulatively eradicated with HBsAg on Week 72,with the eradication rate 42.95％.After the confounding factors were adjusted,multivariate analysis showed that the high levels of Th1,Th2 and Th1/Th2 were the risk factors for the failed clearance of viruses(P＜0.05).CONCLUSIONS Among the patients with HBV infection,there is difference in the immune level between the CHB patients and the CHB virus carriers.The levels of Th1,Th2 and Th1/Th2 are strongly correlated with the HBV DNA,HBsAg,HBeAg and efficiency of viral clearance during the treatment with entecavir.

AIM: To observe the efficacy of intravitreal Conbercept injection(IVC)in diabetic neovascular glaucoma(NVG).METHODS:Retrospective study. Totally 57 patients(57 eyes)with NVG(stage II)secondary to proliferative diabetic retinopathy(PDR)treated in our hospital were collceted from January 2019 to December 2022. Among them, 30 patients(30 eyes)were treated by IVC and panretinal photocoagulation(PRP)in the observation group, and 27 patients(27 eyes)were treated by PRP in the control group. The best corrected visual acuity(BCVA, LogMAR), intraocular pressure, neovascularization of the iridocorneal angle(NVA), central macular thinkness(CMT)changes and disease progression were analyzed with a follow-up of 2 years.RESULTS: There were no significant differences in baseline characteristics between the two groups(P>0.05). At the last follow-up, the BCVA in the observation group was better than the control group(P<0.05). The intraocular pressure, CMT and progression of NVA in the observation group were less than the control group(all P<0.05). The patients with NVG developed from stage II to stage III in the observation group was less than the control group(P<0.05). In the observation group, the BCVA improved compared with preoperative at 6 mo(P<0.05). In the control group, the BCVA decreased compared with preoperative after 24 mo(P<0.05). Multiple linear regression analysis indicated that NVG progression and intraocular pressure were factors affecting BCVA(LogMAR)changes(β=0.511, 0.014; t=4.461, 2.092; P<0.01, 0.041, respectively). In the observation group, the IOP decreased at 1, 6 and 12 mo compared with preoperative(all P<0.05), while there were no significant differences at 18 and 24 mo compared with preoperative(all P>0.05). In the control group, the intraocular pressure decreased at 6 mo compared with preoperative(P<0.05), while there were no significant differences at 1, 12, 18 and 24 mo compared with preoperative(all P>0.05). There were no significant difference about the types of glaucoma drugs between the observation group and the control group(all P>0.05). There were no infectious endophthalmitis and other complications observed in both groups.CONCLUSION: IVC combined with PRP demonstrates superior efficacy over PRP monotherapy in treating NVG(stage II)secondary to PDR. IVC combined with PRP showed better outcomes in controlling iris neovascularization, slowing visual impairment progression, reducing intraocular pressure, and delaying disease advancement.

OBJECTIVE To explore the levels of helper T lymphocytes(Th)in patients with hepatitis B virus(HBV)infection who were treated with entecavir and observe the impact on viral clearance.METHODS A total of 149 patients with HBV infection who were treated with entecavir in Yan'an Hospital of Kunming City from Jan.2020 to Jan.2024 were enrolled in the study,82 of whom were chronic hepatitis B(CHB),and 67 were chro-nic hepatitis B virus carriers.The enrolled patients were divided into the clearance group with 64 cases and the no clearance group with 85 cases according to the levels of serum hepatitis B surface antigen(HBsAg)at Week 72 of the treatment.The clinical data were compared between the two groups,and the changes of Th1 and Th2 levels during the treatment were analyzed.Multivariate linear regression analysis was performed for the association be-tween virological change during the treatment and immune level.The risk factors for failed clearance of viruses were analyzed by logistic regression model.RESULTS There were significant differences in the age,the levels of alanine aminotransferase(ALT)and HBV DNA between the baseline and Week 24,the levels of aspartate trans-aminase(AST)at the baseline and Week 12,the HBsAg level at Week 24,and the baseline levels of Th1,Th1/Th2 between the CHBc treatment group and the CHB treatment group(P＜0.05).There were linear correlations between the HBV DNA,HBsAg,hepatitis E antigen(HBeAg)and the Th1,Th2 and Th1/Th2,respectively(P＜0.05).Totally 64 patients were accumulatively eradicated with HBsAg on Week 72,with the eradication rate 42.95％.After the confounding factors were adjusted,multivariate analysis showed that the high levels of Th1,Th2 and Th1/Th2 were the risk factors for the failed clearance of viruses(P＜0.05).CONCLUSIONS Among the patients with HBV infection,there is difference in the immune level between the CHB patients and the CHB virus carriers.The levels of Th1,Th2 and Th1/Th2 are strongly correlated with the HBV DNA,HBsAg,HBeAg and efficiency of viral clearance during the treatment with entecavir.

【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

AIM: To investigate the protective effect and mechanism of Danlou tablet on retinal ischemia-reperfusion injury(RIRI)in mice.METHODS: A total of 40 ApoE-/- mice were fed with high fat diet for 6 wk, and the RIRI model was established by anterior chamber infusion of pressurized saline. The mice were divided into control group(normal saline for 8 wk), RIRI model group(normal saline for 8 wk), and low-, medium-, and high-dose Danlou tablets groups [1, 2, and 4 g/(kg·d), respectively, for 8 wk]. The morphological changes of retina were observed by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated Nick-End Labeling(TUNEL)staining. The Western-blot assay was used to detect the expression of retinal tissue sample Kelch-like ech-associated protein 1(Keap1), nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), and superoxide dismutase(Sod2)proteins.RESULTS: Compared with the control group, the mouse retina was atrophic with thinning thickness and increasing cell apoptosis, down-regulation of Sod2 protein expression, and up-regulation of Keap1 protein expression in the RIRI model group(all P<0.01). Compared with the RIRI model group, the retinal thickness increased in the medium- and high-dose of Danlou tablets groups(all P<0.01), and the cell apoptosis of retina decreased in the low-, medium- and high-dose of Danlou tablets groups(all P<0.05). There were no significant differences in the expression of Keap1 and HO-1 proteins of mouse retina tissue in the low-dose of Danlou tablets group(P>0.05). The expression of Sod2, Nrf2 and HO-1 proteins up regulated, and the expression of Keap1 protein down regulated in the medium- and high-dose of Danlou tablets groups(all P<0.05).CONCLUSION: Danlou tablet can alleviate RIRI-induced atrophy and thinning of retina and retinal cell apoptosis by regulating Keap1-Nrf2/HO-1 signal pathway and reducing oxidative stress.

Objective To investigate the value of serum high mobility group B1(HMGB1)and vascular endothelial growth factor A(VEGFA)levels in diagnosing the diabetic retinopathy(DR)and predicting the prognosis of patients.Methods A total of 202 patients with type 2 diabetes mellitus(T2DM)admitted to the hospital from January 2021 to January 2022 were selected and divided into DR group(143 cases)and T2DM group(59 cases)based on whether DR occurred or not.According to the degree of lesions,DR groups were di-vided into proliferative DR(PDR)group(76 cases)and non PDR(NPDR)group(67 cases).The DR group was followed up for 1 year,and was divided into poor prognosis group(43 cases)and good prognosis group(143 cases)according to the occurrence of visual disability.46 healthy volunteers who underwent the physical examination during the same period were selected as the control group.Serum HMGB1 and VEGFA levels were measured by enzyme-linked immunosorbent assay.Pearson correlation was used to analyze the correla-tion between serum HMGB1 and VEGFA levels in patients with DR.Multivariate Logistic regression was used to analyze the factors affecting the occurrence of DR and the prognosis of patients with DR,and receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum HMGB1 and VEGFA levels for DR and the predictive value for poor prognosis in patients with DR.Results Serum HMGB1 and VEGFA levels increased sequentially in the control group,the T2DM group,the NPDR group,and the PDR group(P＜0.05).Pearson correlation analysis showed that there was a positive correlation between serum HMGB1 and VEGFA levels in DR patients(r=0.730,P＜0.001).After 1-year follow-up,the incidence of poor prognosis in 143 DR patients was 30.07％(43/143).Multivariate Logistic regression analysis showed that prolonged duration of T2DM,elevated glycosylated hemoglobin(HbA1c)level,elevated HMGB1 level,and elevated VEGFA level were independent risk factors affecting the occurrence of DR and poor prognosis of patients with DR(P＜0.05).ROC curve analysis showed that the area under the curve of the combined detec-tion of serum HMGB1 and VEGFA levels for diagnosing DR and predicting poor prognosis in patients with DR were 0.871 and 0.867,respectively,which were larger than 0.784,0.800 and 0.772,0.780 of the diagnosis and prediction of serum HMGB1 and VEGFA levels alone(P＜0.05).Conclusion Elevated serum HMGB1 and VEGFA levels in DR patients are closely associated with the occurrence of DR and poor prognosis in DR patients,and the combination of serum HMGB1 and VEGFA levels has high value for the diagnosis of DR and the prediction of poor prognosis in DR patients.

Objective:To analyze the changes in the retinal and choroidal microvascular structures in the macular region of patients with acute central serous chorioretinopathy (CSC), as well as the influencing factors of subretinal fluid (SRF) volume.Methods:A prospective selection of 37 patients with monocular acute CSC diagnosed by ophthalmology examination at the Xi ′an First Hospital from January to October 2023 was conducted. The affected eye group was Group A, and the contralateral eye was Group B. The right eye of 30 age and gender matched normal individuals during the same period was selected as the normal eye group (group C). The scanning frequency source optical coherence tomography (SS-OCTA) was used to scan the macular area of the tested eye within a range of 6 mm×6 mm. We analyzed and recorded the vascular density (VD), perfusion area (PA), retinal thickness (RT), choroidal thickness (CT), as well as choroidal vascular volume (CVV) and choroidal vascular index (CVI) of the superficial and deep retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) in the macular area of 0-1 mm, 0-3 mm, and 0-6 mm using our own software. At the same time, we recorded the volume of SRF in the affected eye group. We compared the changes in VD, PA, RT, CT, CVV, and CVI among three groups. The Spearman rank correlation test was used to analyze the correlation between SRF volume and microvascular structural parameters.Results:(1) There was no statistically significant difference in VD and PA of SCP between the affected eye group and the contralateral eye group within the range of 0-6 mm in the macular area (all P>0.05); The VD and PA of SCP in the affected eye group and the contralateral eye group were lower than those in the normal eye group, and the differences were statistically significant (all P<0.05); The VD and PA of DCP in the affected eye group were lower than those in the contralateral eye group, and the difference was statistically significant (all P<0.05). Within the range of 0-3 mm in the macular area, the VD and PA of DCP in the affected eye group and the contralateral eye group were lower than those in the normal eye group, and the differences were statistically significant (all P<0.05). The RT of the affected eye group was higher than that of the contralateral eye group, and the RT of the contralateral eye group was higher than that of the normal eye group, with statistical significance (all P<0.05). (2) Within the range of 0-6 mm in the macular area, the CT of the affected eye group was higher than that of the contralateral eye group, and the CT of the contralateral eye group was higher than that of the normal eye group, with statistical significance (all P<0.05). There was no statistically significant difference in the CVV and CVI of the choroidal vessels between the affected eye group and the contralateral eye group (all P>0.05); The CVV and CVI of the choroidal vessels in the affected eye group and the contralateral eye group were higher than those in the normal eye group, and the differences were statistically significant (all P<0.05). (3) The volume of SRF is negatively correlated with the VD of DCP within the range of 0-3 mm in the macular area ( P<0.05), and positively correlated with CT within the range of 0-6 mm ( P<0.05). Conclusions:Acute CSC is a binocular choroidal disease, and choroidal thickening is mainly due to the thickening of the large and medium vascular layers; Acute CSC can cause a decrease in superficial and deep retinal blood flow density in the macular region; The volume of SRF is negatively correlated with the VD of DCP and positively correlated with CT.

Abstract Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Early life social experience assessment before symptoms of ASD might be helpful for determining the causal link between social experiences and early childhood ASD. Younger children are exposed to excessive screen time in recent years. This paper summarizes the association between screen exposure with ASD in preschool children, and proposes future research directions and provides evidencebased guidance to optimize and support children s early media experiences.

ObjectiveTo investigate the anti-inflammatory effect of the component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on the rat model of rheumatoid arthritis （RA） and the mechanism. MethodSeventy-two SPF-grade SD rats （male and female） aged 5 to 6 weeks were selected. Except the blank group， the rat model of collagen-induced arthritis （CIA） was replicated by the type Ⅱ collagen induction method. The 64 rats after successfully modeling were randomly divided into model group， methotrexate group （0.375 mg·kg^-1）， gentianoside with magnoflorine group （150.454 1 mg·kg^-1+5.061 8 mg·kg^-1）， gentianoside with clematichinenoside AR group （150.454 1 mg·kg^-1+16.433 1 mg·kg^-1）， sweroside with magnoflorine group （3.455 8 mg·kg^-1+5.061 8 mg·kg^-1）， sweroside with clematichinenoside AR group （3.455 8 mg·kg^-1+16.433 1 mg·kg^-1）， swertiamarin with magnoflorine group （9.303 2 mg·kg^-1+5.061 8 mg·kg^-1）， and swertiamarin with clematichinenoside AR group （9.303 2 mg·kg^-1+16.433 1 mg·kg^-1）， with 8 rats in each group. Each group was given the corresponding medicinal solution or normal saline by gavage for 15 d. During the experiment， the general status， of rats in each group were observed and recorded. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， rheumatoid factor （RF）， C reactive protein （CRP）， prostaglandin E₂ （PGE₂）， and anti-cyclic peptide containing citrulline antibody （anti-CCP Ab） in the serum of rats were measured by enzyme-linked immunosorbent assay （ELISA）. The histopathological changes in rat ankle joints were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression of nuclear factor-κB （NF-κB） and vascular endothelial growth factor （VEGF） in rat ankle joints. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NF-κB and VEGF in rat ankle joints. ResultCompared with those in the blank group， rats in the model group were in poor general conditions with significant foot-plantar swelling， and the content of CRP， anti-CCP Ab， and IL-1β in the rat serum was significantly increased （P<0.01）. In the model group， the tissue structure of the ankle joint was severely damaged， and the protein and mRNA expression of NF-κB and VEGF in the rat ankle joints were significantly up-regulated （P<0.01）. As compared with the model group， the general status of rats in each administration group was significantly improved. The levels of serum TNF-α， IL-1β， RF， CRP， PGE₂， and anti-CCP Ab were reduced to different degrees in these administration groups， among which the effects of the gentianoside with clematichinenoside AR group on down-regulating serum TNF-α and IL-1β， the gentianoside with magnoflorine group on down-regulating serum RF and CRP， the sweroside with magnoflorine group on down-regulating serum PGE₂， and the swertiamarin with clematichinenoside AR group on lowering serum anti-CCP Ab were better than those of administration groups. The histopathological changes in the ankle joint were improved to different degrees. The protein and mRNA expression of NF-κB and VEGF in rat ankle joints in the administration groups was significantly down-regulated （P<0.05， P<0.01）， and the swertiamarin paired with clematichinenoside AR group had the most significant effect. ConclusionThe component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma exerts a good therapeutic effect on the rat model of RA， and the compatibility of components from the two medicines has a multi-channel， multi-target， and synergistic effect. The five component compatibility patterns， namely gentiobioside with magnoflorine， gentiobioside with clematichinenoside AR， sweroside with clematichinenoside AR， swertiamarin with magnoflorine， and swertiamarin with clematichinenoside AR， all have potential advantages. The mechanism may be related to the reduction of inflammatory factor secretion and the inhibition of abnormal protein and mRNA expression of NF-κB and VEGF.