Safety and efficacy of lacrimal canalicular plug in the treatment of severe chronic ocular graft-versus-host disease / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the safety and efficacy of lacrimal canalicular plug in the treatment of severe chronic ocular graft-versus-host disease(coGVHD).METHODS: Retrospective study. A total of 9 patients with severe coGVHD admitted to the dry eye clinic of the Affiliated Hospital of Xuzhou Medical University from June to September 2022 were included. All patients underwent binocular inferior lacrimal canaliculus plug. Ocular surface disease index(OSDI)score, tear meniscus height(TMH), corneal fluorescein staining(CFS)scores, conjunctival lisamine green staining(CLGS)score, noninvasive breakup time(NIBUT), Schirmer Ⅰ test(SⅠt)and the infiltration of Langerhans cells in the superficial corneal stroma tested by confocal corneal microscopy were observed before treatment and at 1 and 3 mo after treatment. At the same time, the complications related to lacrimal canalicular plug implantation were evaluated.RESULTS: The OSDI score decreased from 67.33±12.64 before treatment to 21.89±6.07 after 3mo of treatment(P<0.01); TMH increased from 0.09±0.02mm to 0.21±0.03mm after 3mo of treatment(P<0.05), and NIBUT increased from 2.24±0.68s before treatment to 6.77±2.05s after 3mo of treatment(P<0.01). In addition, the CFS and CLGS also changed significantly, from 9.11±1.45 and 6.33±1.00 before treatment to 2.22±0.67 and 2.56±0.88 at 3mo after treatment, respectively(all P<0.01). The density of Langerhans cells decreased from 140.22±38.18cells/mm2 before treatment to 39.67±9.75cells/mm2 3mo after treatment(P<0.01). SⅠt showed no significant difference before and after treatment(F=0.059, P=0.943). During the whole follow-up period, no complications such as plug abscission were observed.CONCLUSION: Lacrimal canalicular plug is safe and effective in the treatment of severe coGVHD. It can significantly improve the symptoms and signs of dry eye patients and reduce inflammatory reaction.

Effects of long-term oral administration of antipsychotic clozapine on the ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the effects of long-term use of clozapine on tear film stability and ocular surface tissue structure.METHODS: Case-control study was conducted on 45 patients(group 1)who were diagnosed with schizophrenia and treated with clozapine for 3.45±0.72a between March 2021 and December 2021. Another 45 healthy subjects(group 2)served as controls, whose demographic characteristics were similar to those of group 1. Patients' dry eye symptoms were investigated using OSDI questionnaire, tear secretion was detected by the Schirmer I test, ocular surface damage was assessed by the ocular surface staining score, and comprehensive ophthalmic examination was performed on all patients through LipiView ocular surface interferometer, ocular surface integrated analyzer, corneal confocal microscope and slit lamp photographic system.RESULTS: Slit-lamp photography showed diffuse grayish-white spot-like opacification in the corneal stroma of group 1, accompanied by brown star-like opacification in the center of the anterior capsule of the lens. OSDI scores were 38.00(31.50, 48.50)and 15.00(9.00, 19.50)in the two groups respectively. Schirmer test showed that the group 1 was 5.27±2.18mm/5min, while group 2 was 15.62±3.05mm/5min. Corneal fluorescein staining score: 4.00(2.50, 5.00)for group 1 and 1.00(0.00, 1.50)for group 2. The lissamine green staining score for the conjunctiva was 9.00(6.50, 10.00)and 3.00(2.00, 3.50)for the two groups, respectively. LipiView detected lipid layer thickness(LLT), suggesting that the results of group 1 and group 2 were similar, respectively 75.91±15.51 and 77.24±12.11nm; and the results were similar for the lid gland deficiency score, with 1.37±0.26 and 1.29±0.31 points, respectively. The mean tear meniscus height in group 1 was 0.13±0.06mm, which was lower than 0.23±0.04mm of group 2. Non-invasive breakup time(NIBUT)was 6.04±2.62 and 11.4±2.74s in group 1 and group 2 respectively. OSDI score, Schirmer Ⅰ test, ocular surface staining score, tear meniscus height and NIBUT were significantly different between the two groups(P<0.05). Confocal corneal microscopy suggested decreased corneal nerve fiber density with stromal layer inflammatory cell infiltration and pigmentation in group 1.CONCLUSION: The antipsychotic drug clozapine can induce dry eye with a range of ocular surface injuries such as corneal pigmentation, and patients who taking such drugs should be routinely examined by an ophthalmologist.

Analysis of interleukin-36 expression in tears of allogeneic hematopoietic stem cell transplantation patients and its correlation with the ocular surface microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the expression of interleukin(IL)-36(α, β, γ)in tears of patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT), investigate its correlation with ocular surface microenvironment, and further analyze the relationship between its expression and ocular graft-versus-host disease(oGVHD).METHODS: Prospective study. A total of 35 patients(70 eyes)underwent allo-HSCT in the hematology department of our hospital in January 2020 were selected, and 35 healthy volunteers(70 eyes)with appropriate age and gender were selected as normal control group. The patients in the allo-HSCT group were followed up 3 times after operation once every 3mo. The subjects with postoperative ocular symptoms were divided into oGVHD and Non-oGVHD group.Ocular surface disease index(OSDI)questionnaire, Schirmer test, tear break-up time(TBUT), corneal fluorescein staining(FL), and conjunctival impression cytology(CIC)was conducted in three groups. Furthermore, the expression levels of IL-36(α,β,γ)in tears were detected by ELISA.RESULTS: In the normal control group, IL-36(α, β, γ)expression levels were 74.32±5.27, 70.02±8.43, 97.41±8.66 pg/mL, respectively; in the allo-HSCT group, IL-36(α, β, γ)baseline expression levels were 77.27±7.03, 74.53±7.53, 100.77±9.74 pg/mL, with no statistically significant differences between the two groups(t=1.648, 1.954, 1.262, all P>0.05). There were no significant differences in IL-36α, IL-36β and IL-36γ in Non-oGVHD group at different time points(P>0.05), while there were significant differences in IL-36α, IL-36β and IL-36γ in oGVHD group at different time points(P<0.05). Compared with Non-oGVHD group, the levels of IL-36α and IL-36β at different time points were significantly increased in oGVHD group(all P<0.05).IL-36(α, β, γ)of oGVHD group was positively correlated with OSDI score, FL and CIC, while it was negatively correlated with TBUT and Schirmer test(all P<0.05).CONCLUSION: Evaluation of levels of tear IL-36(α, β, γ)can be of significance in diagnosing oGVHD after allo-HSCT. IL-36(α, β, γ)is highly expressed in the tears of oGVHD patients before the onset of ocular symptoms, and it is correlated with the ocular surface parameters.

Safety and efficacy of intense pulsed light in the treatment of severe chronic ocular graft-versus-host disease / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the safety and efficacy of intense pulsed light in the treatment of severe chronic ocular graft-versus-host disease.METHODS: Prospective randomized controlled study. A total of 35 cases(35 eyes), who had a history of allogenic hematopoietic stem cell transplantation(allo-HSCT), admitted to the Affiliated Hospital of Xuzhou Medical University from January to September 2022 and were diagnosed by our hospital's hematology and ophthalmology departments with severe chronic ocular graft-versus-host disease(coGVHD)were selected. One eye was randomly selected for inclusion in the study if both eyes met the enrollment criteria, and the eye was selected if a single eye met the enrollment criteria. All patients were administrated with Dextran and Hypromellose eye drops 4 times a day and Cyclosporine eye drops twice a day. The experimental group was additionally treated with intense pulsed light, once every two weeks a week, for 4 times in total. The evaluation indicators were evaluated before treatment and 2wk, 1 and 2mo after treatment. The evaluation indicators include ocular surface disease index(OSDI)score, best corrected visual acuity(BCVA), intraocular pressure(IOP), tear meniscus height(TMH), non-invasive break-up time(NIBUT), conjunctival injection score(CIS), meibomian gland area proportion(MGAP), meibomian gland evaluation(MGE), cornea fluorescein staining(CFS), conjunctival lissamine green staining(CLGS), lid margin abnormality score(LMAS), and Schirmer's Ⅰ test(SⅠt).RESULTS: After treatment, OSDI score, TMH, NIBUT, BCVA, CFS, CLGS, and CIS improved in both groups compared with those before treatment(all P<0.05), with NIBUT, CFS and CLGS showing more significant improvements in the test group. In the control group, MGAP, MGE of the upper and lower eyelids and LMAS did not change significantly before and after treatment(P>0.05), while in the experimental group, MGAP of the lower eyelids, MGE of upper and lower eyelids and LMAS improved compared with those before treatment(P<0.05), except for MGAP of the upper eyelids, which did not differ from that before treatment(P>0.05). There was no difference in SⅠt and IOP between the two groups before and after treatment(P>0.05). Patients did not experience adverse reactions such as skin burns, redness and swelling in the treated area and eyelash loss during the follow-up period.CONCLUSION: Intense pulsed light is safe and effective in the treatment of severe coGVHD, which can significantly improve the symptoms and signs of patients and enhance the stability of tear film.

Problems and countermeasures in the research of oncolytic virus anti-glioma treatment / 中国肿瘤生物治疗杂志

@#[摘 要] 神经胶质瘤是人脑中最常见的原发性肿瘤，占中枢神经系统恶性肿瘤的81%，当前标准疗法仍是手术切除及术后放化疗。因神经胶质瘤具有高侵袭性、分子异质性、治疗后耐药肿瘤干细胞可再生，以及化疗药物难以通过血脑屏障（BBB）达到足够高的治疗浓度等特点，导致其预后非常差，患者中位存活期仅为15个月。近年来，新兴的溶瘤病毒免疫疗法治疗神经胶质瘤的研究备受关注并取得一定进展，但依然面临诸如BBB、免疫“冷”微环境、宿主抗病毒反应和肿瘤高度异质性等挑战。这些问题限制了溶瘤病毒疗法的深入发展及进一步应用，但也给基础与临床研究者带来新的研究机遇。因此，本文从穿越BBB、改善肿瘤微环境（TME）、调控溶瘤病毒介导的宿主免疫反应和适应肿瘤异质性等四个方面，阐述溶瘤病毒在抗神经胶质瘤治疗研究中的存在问题及对策。

Clinical analysis of P2Y2 receptor agonist in the treatment of diabetic dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of P2Y2 agonist diquafosol sodium(DQS)eye drops in the treatment of diabetic dry eye.METHODS: A total of 80 patients(160 eyes)with diabetic dry eye who admitted to our hospital from January 2022 to March 2022 were selected. They were randomly divided into study group and control group. A total of 40 patients(80 eyes)in the study group were treated with 3% DQS eye drops and 40 patients(80 eyes)in the control group were treated with 0.3% sodium hyaluronate eye drops. The ocular surface disease index(OSDI)score, non-invasive tear meniscus height(NITMH), first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tarsal gland loss score, lipid layer thickness grade and bulbar redness analysis(including conjunctival grade and ciliary grade), were examined before treatment and at 1wk, 1 and 3mo after treatment, respectively. Furthermore, corneal fluorescence staining and conjunctival lissamine green staining were analyzed based on the ocular surface staining score(OSS), and the conjunctival impression cytology and confocal microscopy were evaluated before and 3mo after treatment, respectively.RESULTS: There were no differences in OSDI score, tarsal gland loss score, conjunctival grade score and ciliary grade score between the two groups before and after treatment(P>0.05). OSS scores in the study group were lower than those in the control group, while NITMH, NIBUTf and NIBUTav were higher than those in the control group at 1 and 3mo after treatment(P<0.05). After 3mo of treatment, the density of conjunctival goblet cells increased and corneal dendritic cells decreased in the study group compared with the baseline(all P<0.05), while there were no significant changes in the control group compared with the baseline(all P>0.05).CONCLUSION: 3% DQS eye drops were effective in treating diabetic dry eye without serious complications.

Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

Population structure of food-borne Staphylococcus aureus in China / 中华流行病学杂志

Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.

Prediction of superantigen active sites and clonal expression of staphylococcal enterotoxin-like W / 中华流行病学杂志

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.

Factors affecting nasal drug delivery and design strategies for intranasal drug delivery / 浙江大学学报·医学版

Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China.@*METHODS@#A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined.@*RESULTS@#BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan).@*CONCLUSION@#BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.

Prostate cancer with normal serum PSA: a report of 6 cases and literature review / 现代泌尿外科杂志

【Objective】 To analyze the clinical data of prostate cancer patients with normal PSA level confirmed with transperineal prostate biopsy or transurethral prostate surgery, in order to improve the diagnostic level of this disease. 【Methods】 The clinical data of 6 patients were retrospectively analyzed. The age,clinical manifestations, body mass index (BMI),prostate specific antigen density (PSAD),blood triglycerides,blood cholesterol,color ultrasound imaging,magnetic resonance imaging (MRI),pathological types and Gleason scores were analyzed. The clinical characteristics and high-risk factors were summarized. 【Results】 Two cases were confirmed with prostate biopsy and four after prostate resection. Three patients had high blood triglycerides, three were negative for bone imaging, and the other three were not examined. PSAD was 0.017 to 1.215. Color ultrasound indicated that two cases had irregular morphology, two uneven echo, and one both irregular morphology and uneven echo; all six cases had calcification. In the three cases who received MRI, two had PIRADS4 nodules, one had PIRADS5 nodules, invasion of seminal vesicle, rectum, posterior wall of urinary bladder,bilateral thickening of NVB, and lymph nodes enlargement. Pathology suggested prostatic acinar adenocarcinoma in five cases, four of which had a Gleason score of 3+3=6 and one had 5+5=10; one case suggested a high-grade neuroendocrine carcinoma. 【Conclusion】 The clinical detection rate is low for prostate cancer with normal PSA. The biopsy indications should be determined by combining the characteristics and high-risk factors to improve the detection rate.

Analysis of subtypes and risk characteristics of depression and anxiety among primary and secondary school students / 中国学校卫生

Objective@#To understand different types of depression and anxiety among primary and secondary school students, as well as their influencing factors, so as to provide a basis for the development of future intervention programs for adolescent mental health.@*Methods@#From December 2022 to February 2023, a self administered questionnaire survey was administered among grades 4 to 6 students and junior school, senior school students in Yixing City using Depression Anxiety and Stress Scale-21 (DASS-21), Insomnia Severity Index (ISI), Family Environment Scale (FES), and modified Yale Food Addiction Scale 2.0 (mYFAS 2.0), Ottawa Self injury Inventory (OSI). A total of 4 180 students were included in the analysis. Different types of depression and anxiety in students and their influencing factors were analyzed by the Chi squaretest and multivariate Logistic regression.@*Results@#The overall prevalence of depression and anxiety among primary and secondary school students were 16.6% and 22.4%, respectively, with 14.0% of depression and anxiety comorbidities. The Logistic regression results showed that, compared to students with low depression-low anxiety, students of depression and anxiety who had parents in conflicts ( OR =3.06), smoked ( OR =3.16), exhibited moderate food addiction ( OR =3.56), and had non suicidal self injury (NSSI) ( OR =2.26) were more likely to be classified as a depression predominant-depression anxiety type. Students of depression and anxiety who consumed alcohol ( OR =2.00), had serious food addiction ( OR =5.44), moderate to severe insomnia ( OR =3.25), and mild insomnia ( OR =1.88) were more likely to be classified as anxiety predominant-depression anxiety type. Students of depression and anxiety with low mood ( OR =10.87), mild food addiction ( OR =2.00), moderate food addiction ( OR =4.32), and severe food addiction ( OR =7.35), mild ( OR =2.96) or moderate to severe ( OR =16.52) insomnia, and NSSI ( OR =4.24) were more likely to be classified as the severe depression anxiety type( P < 0.05 ).@*Conclusions@#There are significant differences between different depression-anxiety types among primary and secondary school students with respect to food addiction, insomnia, NSSI, smoking, and alcohol use. Relevant departments should engage with schools and families to adopt targeted interventions for students to reduce the occurrence of mental health problems.

Association between negative emotion, family intimacy and Internet addiction among junior and senior school students / 中国学校卫生

Objective@#To explore the association between negative emotion (depression, anxiety and stress), family intimacy and Internet addiction, so as to provide a basis for the intervention of Internet addiction among junior and senior high school students.@*Methods@#Students were selected by stratified random cluster sampling method from junior high schools and senior high schools from December 2022 to February 2023 in Yixing City, Jiangsu Provicne. A total of 3 026 students completed the questionnaire survey, including the demographic characteristics, Depression, Anxiety and Stress Scale-21 (DASS-21), Family Environment Scale-Chinese Version (FES-CV), and Chinese Internet Addiction Scale Revised (CIAS-R). Bivariate correlation was used to analyzed the association of family intimacy, depression, anxiety, stress, and Internet addiction. Mediating effect model was used to analyzed the mediating effect of negative emotion between family intimacy and Internet addiction.@*Results@#The average score of Internet addiction among junior and senior high school students was (46.26±15.58), and there were statistical differences in the average scores of Internet addiction across different grades ( F=87.15, P <0.01). Depression ( r =0.57), anxiety ( r =0.56), stress ( r = 0.57) were positively correlated with Internet addiction, and family intimacy ( r =-0.34) was negatively correlated with Internet diction ( P <0.01). In the mediating effect model, family intimacy negatively predicted negative emotion ( β =-0.48) and Internet addiction ( β =-0.10), and negative emotion positively predicted Internet addiction ( β =0.45) ( P <0.01). Negative emotion played a partial mediating role between family intimacy and Internet addiction (the mediation value:-1.71, 95% CI =-1.96--1.49, mediation ratio:67.9%, P <0.05).@*Conclusions@#There are associations between negative emotion, family intimacy and Internet addiction among junior and senior school students. Family intimacy indirectly affects Internet addiction mainly through negative emotion. It suggests that family education is in need of attention to reduce the prevalence rate of Internet addiction among junior and senior high school students, especially family intimacy.

Association of anxiety, insomnia, and family cohesion with Internet addiction and non suicidal self injury behavior in junior and senior school students / 中国学校卫生

Objective@#To explore the mediating effect of anxiety, insomnia, and family cohesion between Internet addiction and non suicidal self injury (NSSI) behavior among junior and senior school students, so as to develop interventions to promote adolescent mental health.@*Methods@#A total of 3 026 junior and senior school students from Yixing, Jiangsu Province, China, were selected by stratified cluster sampling from December 2022 to February 2023, and were administered the Ottawa Self injury Inventory (OSI), Depression, Anxiety and Stress Scale-21 (DASS-21), Family Environment Scale-Chinese Version (FES-CV), Insomnia Severity Index (ISI), and Chinese Internet Addiction Scale Revised (CIAS-R). A mediating effect model was constructed to analyze the mediating effect of anxiety, insomnia, and family cohesion on Internet addiction and NSSI.@*Results@#Internet addiction ( r = 0.24), insomnia ( r =0.28), and anxiety ( r =0.27) were positively correlated with NSSI, while the latter was negatively correlated with family cohesion ( r =-0.23) ( P <0.01). The mediating effect model was well fitted ( CFI=0.999, TLI=0.978, RMSEA = 0.030 ). Anxiety (mediation effect value:0.12, 95% CI =0.08-0.18) and family cohesion (mediation effect value:0.08, 95% CI = 0.03 -0.13) had a separate mediating effect. A chain meditating effect was found in the case of anxiety and insomnia (mediation effect value:0.14, 95% CI =0.10-0.20), family cohesion and anxiety (mediation effect value:0.05, 95% CI =0.03-0.07), family cohesion and insomnia (mediation effect value:0.05, 95% CI =0.03-0.07), and family cohesion, anxiety, and insomnia (mediation effect value:0.06, 95% CI =0.04-0.08). The mediating effect accounted for 14.9%, 10.1%, 17.5%, 6.0%, 5.6%, and 7.1%, respectively.@*Conclusions@#Anxiety, insomnia, and family cohesion partially mediate Internet addiction and NSSI. Schools and families should pay attention to Internet addiction among junior and senior school students and develop appropriate interventions to promote adolescent mental health, so as to reduce the prevalence of NSSI.

Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation / 中国当代儿科杂志

OBJECTIVES@#To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance.@*METHODS@#A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission.@*RESULTS@#A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05).@*CONCLUSIONS@#Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Joint association of sedentary behavior and physical activity on anxiety tendency among occupational population in China / 北京大学学报(医学版)

OBJECTIVE@#To investigate the status and influencing factors of anxiety tendency among occupational population in China and to examine the joint association between sedentary behavior and physical activity with anxiety tendency.@*METHODS@#The data were from the 2021 Asia Best Workplace (Chinese mainland) program. The Generalized Anxiety Tendency scale was used to assess employees' anxiety status, and Logistic regression was used to analyze the factors influencing anxiety tendency and calculate the odds ratio (OR) within different groups. The OR of sitting for each sitting-physical activity (PA) combination group and within PA strata were calculated to explore the joint association.@*RESULTS@#A total of 11 903 workers with an average age of 32.9 years were included in this study. Among them, 3 562 workers had anxiety tendency (29.9%) and the prevalence of those under 40 years old (30.6%) was significantly higher than the other age group (26.7%). 41.0% of the respondents had the moderated to vigorous physical activity. Their average daily sitting time was 9.4 h, and the percentage of those who exceeded 8 h sitting reached 73.9% in the past week. The analysis of Logistic regression showed that smoking (OR=1.24, 95%CI: 1.23-1.39), longer sedentary time and lower physical activity level were risk factors for anxiety tendency, and longer average daily sleep time (OR=0.56, 95%CI: 0.51-0.61) was a protective factor. The joint association analysis and stratified analysis of physical activity and sedentary behavior with anxiety tendency showed that increased sedentary time combined with decreased physical activity intensity was significantly associated with increased risk of anxiety tendency (range of OR: 1.64-3.14). The threshold for sedentary time in total as a risk factor for anxiety tendency gradually decreased as physical activity intensity increased.@*CONCLUSION@#The anxiety tendency and sedentary behavior among the occupational population should recieve more attention. Lack of physical activity and sedentary behavior are both risk factors for anxiety tendency, and strengthening the intensity of physical activity can attenuate the harmful effects of sedentary behavior on anxiety tendency.

Mechanism of valproic acid-induced dendritic spine and synaptic impairment in the prefrontal cortex for causing core autistic symptoms in mice / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of valproic acid (VPA) -induced impairment of the dendritic spines and synapses in the prefrontal cortex (PFC) for causing core symptoms of autism spectrum disorder (ASD) in mice.@*METHODS@#Female C57 mice were subjected to injections of saline or VPA on gestational days 10 and 12, and the male offspring mice in the two groups were used as the normal control group and ASD model group (n=10), respectively. Another 20 male mice with fetal exposure to VPA were randomized into two groups for stereotactic injection of DMSO or Wortmannin into the PFC (n=10). Open field test, juvenile play test and 3-chamber test were used to evaluate autistic behaviors of the mice. The density of dendrite spines in the PFC was observed with Golgi staining. Western blotting and immunofluorescence staining were used to detect the expressions of p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and the synaptic proteins PSD95, p-Syn, and Syn in the PFC of the mice.@*RESULTS@#Compared with the normal control mice, the mice with fetal exposure to VPA exhibited obvious autism-like behaviors with significantly decreased density of total, mushroom and stubby dendritic spines (P < 0.05) and increased filopodia dendritic spines (P < 0.05) in the PFC. The VPA-exposed mice also showed significantly increased expressions of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR (P < 0.01) and lowered expressions of PSD95 and p-Syn/Syn in the PFC (P < 0.05 or 0.001). Wortmannin injection into the PFC obviously improved the ASD-like phenotype and dendritic spine development, down-regulated PI3K/Akt/mTOR signaling pathway and up-regulated the synaptic proteins in VPA-exposed mice.@*CONCLUSION@#In male mice with fetal exposure to VPA, excessive activation of PI3K/Akt/mTOR signaling pathway and decreased expressions of the synaptic proteins PSD95 and p-Syn cause dendritic spine damage and synaptic development disturbance in the PFC, which eventually leads to ASD-like phenotype.