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.

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 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 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.

Objective:To investigate the effects of insulin glargine administration by jet injection versus conventional insulin pen on glucose profile using professional mode flash glucose monitoring(FGM) system in type 2 diabetic patients with poor glucose control.Methods:In this randomized, controlled, crossover study, 40 patients with T2DM who treated with insulin glargine were enrolled. The patients were randomly divided into group A(jet injector-conventional pen, n=20) and group B(conventional pen-jet injector, n=20). Each patient wore FreeStyle Libre sensor from day 4 to day 17. The specialist nurse instructed patients how to master the injection techniques. Professional FGM system was applied to assess glucose profile. Results:The fasting blood glucose(FBG) of the enrolled patients was(9.37±1.84) mmol/L. In contrast to conventional insulin pen, treatment with the jet injector significantly decreased the 24h MBG [(9.06±2.13 vs 9.98±2.67) mmol/L, P=0.001], MaxBG [(16.69±3.01 vs 17.95±3.48) mmol/L, P=0.001], AUC>10 mmol/L [95.93(21.12, 129.02) vs 142.66( 27.88, 198.46), P=0.002], TAR(31.10±21.89 vs 39.49±25.93, P=0.003), MAGE and SDBG. It was observed that patients using jet injector had significant increased TIR(65.94±20.47 vs 58.32±25.00, P=0.001). There were no difference in the risk of hypoglycaemia between two groups. Conclusion:Insulin jet injector was more effective than the insulin pen on glycaemic control and glucose fluctuation without increasing the risk of hypoglycemia in type 2 diabetic patients with uncontrolled glycemia.

Objective:To observe the correlation between homocysteine (Hcy) and serum uric acid (SUA) and retinopathy in type 2 diabetes mellitus (T2DM), preliminary study on its predictive value.Methods:A retrospective study. From January 2020 to March 2021, a total of 324 T2DM patients hospitalized in Department of Endocrinology, Cangzhou Central Hospital of Hebei Province were included. Fasting blood glucose (FBG), glycated hemoglobin (HbA1C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), serum creatinine (Scr), blood urea nitrogen (BUN), Hcy, SUA, peripheral blood endothelial progenitor cells (EPC), circulating endothelial cells (CEC) were counted and homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. According to the absence or presence of diabetic retinopathy (DR), the patients were divided into non DR (NDR) group and DR group with 100 and 214 cases, respectively. Clinical data and laboratory biochemical indexes of the two groups were compared and observed. The logistic regression was used to analyze the independent risk factors for DR in T2DM patients. Smooth curve fitting was used to analyze the curve relationship between Hcy, SUA and DR, and ROC area (AUC) of Hcy, SUA; their combined prediction of DR in T2DM patients was calculated by receiver operating characteristic curve (ROC curve), and the predictive value of Hcy and SUA for DR in T2DM patients was evaluated.Results:Diabetic course ( t=5.380), systolic blood pressure ( t=2.935), hypertension ( χ2=10.248), diabetic nephropathy ( χ2=9.515), diabetic peripheral neuropathy ( χ2=24.501), FBG ( t=3.945), HbA1C ( t=3.336) and TG in DR Group ( t=2.898), LDL-C ( t=3.986), Scr ( t=2.139), SUA ( t=7.138), HOMA-IR ( t=3.237), BUN ( t=3.609), Hcy ( t=2.363) and CEC ( t=19.396) were significantly higher than those in NDR group. The difference was statistically significant ( P<0.05). EPC ( t=9.563) and CPC ( t=7.684) levels were significantly lower than those of NDR group, and the difference was statistically significant ( P<0.05). Logistic regression analysis showed that diabetes course, SBP, hypertension, FBG, HbA1C, LDL-C, SUA, Hcy, EPC, CPC and CEC were all independent risk factors for developing DR in T2DM patients ( P<0.05). The smooth curve fitting analysis showed that Hcy and SUA were positively correlated with the occurrence of DR. After adjusting for confounding factors, when Hcy≥15 μmol/L, the risk of DR Increased by 14% for every 1 μmol/L increase in Hcy [odds ratio ( OR)=0.92, 95% confidence interval ( CI) 0.88-0.98, P<0.05]. When Hcy <15 μmol/L, there was no significant difference ( OR=0.96, 95% CI 0.92-1.08, P>0.05). When SUA≥304 μmol/L, the risk of DR increased by 17%, every 20 μmol/L SUA increased ( OR=0.80, 95% CI 0.68-0.94, P<0.05). When SUA <304 μmol/L, the difference was not statistically significant ( OR=0.83, 95% CI 0.72-0.95, P>0.05). ROC curve analysis results showed that the AUC values of Hcy, SUA and Hcy combined with SUA in predicting the occurrence of DR in T2DM patients were 0.775 (95% CI 0.713-0.837, P<0.001), 0.757 (95% CI 0.680-0.834, P<0.001) and 0.827 (95% CI 0.786-0.868, P<0.001). Hcy combined with SUA showed better predictive efficiency. Conclusions:The abnormal increase of Hcy and SUA levels in T2DM patients are closely related to the occurrence of DR, they are independent risk factors for the occurrence of DR. Hcy combined with SUA has high predictive value for the occurrence of DR.

Objective:To observe the clinical characteristics and optical coherence tomography (OCT) features of pseudopapilledema (PPE) combined with peripapillary hyper-reflective ovoid mass-like structures (PHOMS) in children.Methods:A retrospective observational study. From October 2019 to May 2021, total 22 eyes from 12 children diagnosed as PPE combined with PHOMS in the Neuro-ophthalmology Department of The First Hospital of Xi’an (Affiliated of The First Hospital of Northwest University) were recruited. Among the children, 6 were male and 6 were female. The average age was (10.6±2.7) years. The average course from disease onset to diagnosis of PPE combined with PHOMS was (8.0±7.5) months. All patients underwent best corrected visual acuity (BCVA), relative afferent papillary defect (RAPD), Ishihara's test, fundus photography, OCT, fundus autofluorescence (FAF), ocular B-mode ultrasound, visual field and patternvisual evoked potential (P-VEP). The clinical and OCT characteristics of the patients were observed.Results:The anterior segments of the patients were normal. The intraocular pressures and Ishihara's test were all normal. All RAPD were negative. Total 22 eyes, BCVA was 1.0 in 21 eyes and one eye was 0.12. The fundus photography revealed blurred optic discs margin, showing mild to moderate edema-like elevation with more prominent in the nasal parts, presenting as a "C" shape halo. No obvious abnormal fluorescence was observed in FAF. The OCT scan of involvement eyes showed an elevated appearance in vary degrees, and the sharply marginated ovoid hyper-reflective mass-like structures which laterally herniated into the peripapillary region under retinal nerve fiber layer and above the Bruch membrane were detected with consecutive nasal enlargement scanning, corresponding to the nasal parts in the fundus photography. The higher degree of elevation, the larger the volume. Macular retina pigment epithelium layer and ganglion cell thickness were normal. Ocular B-mode ultrasound showed that the head of the optic nerve in the posterior wall of the eyeball (in front of the optic disc) was elevated in all affected eyes, and there was no strong signal echo in it. Visual field examination showed physical blind spot enlargement in 3 eyes and visual field defect in 2 eyes. P-VEP examination showed that the peak was slightly delayed in 3 eyes and the amplitude was slightly reduced in 3 eyes.Conclusions:Enlarged nasal optic disc OCT scan can improve the detection rate of PHOMS. PHOMS were detected bilaterally in the cases with binocular PPE while only in the effected eye in the cases of monocular PPE; the higher degree of PPE, the lager volume of PHOMS. PHOMS were could contribute to the diagnosis of PPE in children.

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.

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.