ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.

Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.
Mice ; Animals ; Interferon-gamma/metabolism* ; Interleukin-17/metabolism* ; Interleukin-33/metabolism* ; Cytokines/metabolism* ; Carbon Tetrachloride ; Th2 Cells ; Interleukin-4/metabolism* ; Liver Cirrhosis/pathology* ; Th1 Cells ; Th17 Cells/pathology* ; Immunity

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Objective: Using two measuring tools to examine the prevalence and correlates of neurocognitive impairment (NCI) as well as characteristics of neurocognitive performance among people with HIV (PWH) on antiretroviral treatment (ART). Methods: A total of 2 250 treated PWH from the Comparative HIV and Aging Research in Taizhou (CHART) were recruited in Taizhou, Zhejiang province. The Chinese version of the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) were used to evaluate their neurocognitive performance. Cluster analysis was conducted on the seven cognitive domains in the scale. Results: Among 2 250 treated PWH, 48.0% (1 080/2 250) were aged 45 to 89, 79.2% (1 782/2 250) were male, and 37.8% (852/2 250) had primary school education or below. The prevalence of neurocognitive impairment judged by MMSE and IHDS among HIV-infected people was 14.3% (321/2 250) and 31.8% (716/2 250), respectively. Aged 60 to 89 (aOR=2.63, 95%CI:1.52-4.56), depressive symptoms (aOR=5.58, 95%CI:4.20-7.40) and treatment with EFV (aOR=2.86, 95%CI:1.89-4.34) were main risk factors of NCI diagnosed by MMSE. Male (aOR=0.71, 95%CI:0.51-1.00), overweight (aOR=0.63, 95%CI:0.44-0.89), and high education level (aOR=0.11, 95%CI:0.05-0.25) were protective factors of NCI diagnosed by MMSE. Aged 60 to 89 (aOR=3.10, 95%CI:2.09-4.59), depressive symptoms (aOR=1.78, 95%CI:1.44-2.20) and treatment with EFV (aOR=1.79, 95%CI:1.41-2.29) were risk factors of NCI diagnosed by IHDS. Male (aOR=0.75, 95%CI:0.58-0.97), underweight (aOR=0.67, 95%CI:0.47-0.96), baseline CD4⁺ T lymphocyte (CD4) counts ≥350 cells/μl (aOR=0.69, 95%CI:0.53-0.91) and high education level (aOR=0.23, 95%CI:0.14-0.39) were protective factors of NCI diagnosed by IHDS. The neurocognitive performance of HIV-infected people can be divided into four main types. Among four types, age, gender, education level, alcohol drinking, depressive symptoms, waist-to-hip ratio, hypertension, diabetes, baseline CD4 counts and treatment with EFV were different statistically (all P<0.05). Conclusions: There are four main types of neurocognitive performance in treated PWH. The prevalence of NCI is high among this population, underscoring the need for tailored prevention and intervention.
Male ; Humans ; Female ; Anti-Retroviral Agents ; Educational Status ; CD4 Lymphocyte Count ; Protective Factors ; HIV Infections/drug therapy*

Objective: To explore the correlation between club drug use and anal canal human papillomavirus (HPV) infection in HIV-negative and HIV-positive men who have sex with men (MSM) in Taizhou. Methods: A cross-sectional survey was conducted in Taizhou. HIV-negative MSM were recruited by convenient sampling in voluntary counseling and testing clinics of Taizhou prefectural CDC from August 2016 to October 2017, and HIV-positive MSM were recruited through the routine follow-up and management by Taizhou prefectural CDC from August 2016 to June 2019. A face-to-face questionnaire interview was conducted to collect the information about the socio-demographic characteristics, sexual orientation, sexual behavior, club drug use and other information of the participants. Anal canal swabs were collected for HPV genotyping. The correlation between club drug use and the prevalence of HPV infection were evaluated with χ² test and logistic regression analysis. Results: A total of 69 HIV-negative and 345 HIV-infected MSM were included. The prevalence of any type of anal canal HPV infection in HIV-negative MSM (27.5%, 19/69) was lower than that in HIV-positive MSM (66.4%, 229/345) (χ²=36.114,P<0.001). The prevalence of self-reported club drug use in HIV-negative MSM was higher (17.4%, 12/69) than that in HIV-positive MSM (7.0%, 24/345) (χ²=7.886, P=0.005). For HIV-negative MSM, the prevalence of club drug use was higher in MSM who had homosexual group sex (P=0.036); the prevalence of HPV infection was 50.0% (6/12) in club drug users and 22.8% (13/57) in non-club drug users (χ²=3.674, P=0.055). For HIV-positive MSM, the prevalence of HPV infection was 70.8% (17/24) in club drug users and 66.0% (212/321) in non-club drug users (χ²=0.230, P=0.632). Multivariable logistic regression model showed that HPV infection in MSM was positively correlated with HIV infection (OR=5.42, 95%CI: 2.92-10.06), and the association between HPV infection and club drug use (OR=1.66, 95%CI: 0.75-3.71) was not significant. Conclusions: HIV infection was positively correlated with anal canal HPV infection in MSM in Taizhou. Club drug use was positively correlated with high-risk sexual behaviors, while its association with HPV infection needs further study.
Anal Canal ; Cross-Sectional Studies ; Female ; HIV Infections ; Homosexuality, Male ; Humans ; Illicit Drugs ; Male ; Papillomaviridae ; Papillomavirus Infections ; Risk Factors ; Sexual Behavior ; Sexual and Gender Minorities

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Cytochrome P450 reductase (CPR) is essential for the electron transport chain of cytochrome P450s, playing an indispensable role in electron transfer in vivo. In this study, one cDNA encoding cytochrome P450 reductase (Ascpr1) was identified from the callus of Aquilaria sinensis. Ascpr1 contains an open reading frame of 2 124 bp. The deduced protein is composed of 707 amino acids, with a predicted molecular weight of 78.82 kD. Phylogenetic analysis revealed that AsCPR1 is a type Ⅱ CPR protein closely related to the CPR from Theobroma cacao. Transmembrane prediction using TMHMM 2.0 indicated that the amino acids 52-71 of AsCPR1 comprise a transmembrane region. After truncating of 67 amino acid residues from N-terminal, the truncated AsCPR1 was successfully expressed in E. coli Transetta (DE3). Further purification of the recombinant AsCPR1 by affinity chromatography and determination of the enzymatic activity allowed the reducing ability of AsCPR1 to cytochrome C in vitro. The results pave the way for further study on the synthesis of defensive chemicals involved in P450s and the functions of CPR in self-defense of A. sinensis.

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.
Curcumin/pharmacology* ; Escherichia coli/genetics* ; Fermentation

ObjectiveTo understand the infection of AIDS， syphilis， and gonorrhea in men who have sex with men （MSM）， and the factors influencing the acceptance of gonorrhea testing in Dehong Dai Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province. MethodsAcross-sectional survey was conducted to describe and analyze the acceptance of AIDS， syphilis， and gonorrhea testing among MSM tracked in Dehong Prefecture in 2018. ResultsA total of 385 MSM were included in the analysis， with a 100.0% HIV and syphilis testing rate. The HIV antibody positivity rate was 10.6% （41/385） and the positivity rate of syphilis antibody was 14.8%（57/385）. Only 30.4% of the subjects were willing to test for gonorrhea， and 13.7%（16/117）of them were test positive. Further multifactorial analysis revealed that local MSM and syphilis co-infected individuals were more likely to be tested for gonorrhea （aOR=2.48， 95%CI=1.33-4.65， P=0.004； aOR=2.59， 95%CI=1.43-4.71， P=0.002）. ConclusionThe positive rates of AIDS， syphilis and gonorrhea in MSM population in Dehong Prefecture are relatively high. Integrated interventions of STD/AIDS and gonorrhoea detection should be strengthened.