Objective: To analyze the association between insufficient sleep and score of depressive symptoms among junior and senior high school students, so as to provide a scientific reference for targeted early intervention measures of adolescents depressive symptoms. Methods: From September to November 2023, a stratified cluster random sampling method was used to select 96 080 junior and senior high school students from 409 schools in 113 districts and counties in Shaanxi Province. A questionnaire survey was conducted using the 2023 Shaanxi Provincial Common Student Diseases and Health Influencing Factors Survey Form, and their height and weight were measured. Propensity score (PS) matched (1∶1) analysis was used to match participants with insufficient sleep to those sufficient sleep students. Through the gradual correction of the confounders, three multilevel linear models were established to analyze the association between insufficient sleep and depressive symptoms score, and subgroup analysis was conducted afterward. Results: A total of 70 135 (73.00%) students had insufficient sleep. After PS matching, 25 894 pairs were matched. Before PS matching, after adjusting for gender, educational stage, region, adolescent characteristics, boarding status, smoking, alcohol consumption, outdoor activities and body mass index grouping, linear regression analysis results showed that compared with students who got adequate sleep, students who lacked sleep had an increase of 1.39 scores ( B=1.39, 95%CI =1.28-1.51) in depressive symptoms; after PS matching, students with insufficient sleep got an increase of 1.32 scores ( B=1.32, 95%CI =1.17- 1.45 ) in depressive symptoms score compared with those who had adequate sleep (both P <0.05). Conclusions The insufficient sleep is associated with the increase of the depressive symptoms score of junior and senior high school students. It is recommended that junior and senior high school students should keep a good sleeping habit, so as to reduce the prevalence of depressive symptoms.

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective To analyze the effects of low-level laser therapy(LLLT)combined with elec-tromyogram-triggered neuromuscular electrical stimulation(ETNS)on upper limb function and quality of life in patients with subacute ischemic stroke.Methods A total of 52 patients with sub-acute ischemic stroke admitted to our hospital from January 2020 to October 2023 were recruited,and then randomly divided into control group(26 cases)and observation group(26 cases).Fugl-Meyer Motor Function Score-Upper Limb(FMA-UE),Trunk Injury Scale(TIS),Wolf Motor Function Test Scale(WMFT)-Time(TS)and Functional Ability(FS),Chinese version of Stroke Quality of Life Scale(SS-QOL)were used before treatment(day of enrollment)and after treat-ment(5 months after enrollment)to evaluate these patients.Results After treatment,the obser-vation group had obviously higher FMA-UE score,TIS score,WMFT-FS score and SS-QOL score than those before treatment(P＜0.05),and these scores were also notably higher than those in control group after treatment(P＜0.01).The WMFT-TS score in the observation group after treatment was statistically lower than that before treatment(P＜0.05),and also reduced than that of the control group after treatment(39.42±11.65 vs 46.12±11.89,P=0.045).Conclusion LLLT combined with ETNS shows good efficacy in improvement of upper limb function and quality of life in subacute ischemic stroke patients.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.

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Objective:To evaluate the clinical significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma. Methods:Patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were eligible. All received 2 cycles of pembrolizumab combined with docetaxel and platinum neoadjuvant induction therapy. After two cycles, the efficacy was evaluated, followed by radical chemoradiotherapy or surgery and adjuvant chemoradiotherapy according to the efficacy. The primary endpoints were objective response rate（ORR） ，larynx-preservation（LP） rate at 3 months post-treatment and the adverse reactions during neoadjuvant therapy. Results:From December 2021 to December 2022, 10 patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were enrolled. After 2 cycles of the neoadjuvant therapy, 2 patients achieved complete response（CR）, 7 patients achieved partial response（PR）, 1 patient was stable disease（SD）, objective response rate（ORR） was 90%, and disease control rate（DCR） was 100%. 5 patients received radical chemoradiotherapy, 5 patients received surgery and adjuvant chemoradiotherapy, four of them received partial laryngectomy and partial hypopharyngeal resection surgery, and one of them received total laryngectomy and partial hypopharyngeal resection surgery. All patients were able to withstand adverse reactions of neoadjuvant therapy and successfully completed the whole treatment of HPSCC without grade 3-4 treatment-related adverse reactions. There was no recurrence or metastasis during 3-18 months of follow-up. 1 patient died of severe pneumonia 3 months after the completion of radical chemoradiotherapy. At 3 months after treatment, the larynx-preservation rate was 80%. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy has good short-term efficacy and the adverse reactions were tolerable. It can improve the larynx-preservation rate of patients with locally advanced HPSCC, thus improving the prognosis and quality of life of patients.
Humans ; Squamous Cell Carcinoma of Head and Neck/etiology* ; Neoadjuvant Therapy ; Quality of Life ; Cisplatin ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Larynx ; Head and Neck Neoplasms ; Immunotherapy

OBJECTIVE To establish the method for content determination of related substances in Oxcarbazepine tablets. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted and the separation was performed on ZORBAX Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate solution （pH6.0） （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was 230 nm and column temperature was set at 35 ℃. The sample size was 10 μL. RESULTS The linear ranges of oxcarbazepine and impurity A， B， C， D， E， I， K， L and N were 0.192-1.440， 1.019-7.639， 0.208-1.559， 0.230-1.727， 0.389-2.915， 0.182-1.364， 0.393-2.945， 0.199-1.493， 0.199-1.490 and 0.200- 1.503 μg/mL， respectively （all r＞0.999）. The detection limits were 0.046， 0.037， 0.049， 0.027， 0.077， 0.040， 0.114， 0.054， 0.055 and 0.039 μg/mL. The quantitation limits were 0.152， 0.122， 0.162， 0.090， 0.258， 0.132， 0.380， 0.181， 0.185 and 0.130 μg/mL. RSDs of precision， repeatability， stability （24 h） and durability tests were all lower than 5.0%. The average recoveries were 92.8%-105.6% （RSD≤3.0%， n＝9）. Only impurity K and unknown impurity were detected in the original preparation sample， with a total content of 0.078% to 0.083%； impurities A， B， D， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅰ， with a total content of 0.147% to 0.163%； impurities A， B， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅱ， with a total content of 0.085% to 0.161%. CONCLUSIONS The established method is rapid， sensitive， accurate， stable and durable. It can be used for the content determination of 9 known impurities in Oxcarbazepine tablets.

OBJECTIVE To establish a reciprocating tube dissolution method to investigate the similarity of in vitro dissolution behavior of oxcarbazepine scored tablet preparations between the original and generic drugs, and to evaluate the differences in dose-specific pharmaceutical properties between the original and generic drugs. METHODS Using 250 mL of pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer, and water(all 0.5% sodium dodecyl sulfate) as the dissolution medium, and reciprocating frequency of 10 dip min-1, using a reciprocating tube dissolution device to determine the dissolution curves of generic drugs and original research drugs, and combining the similarity factor(f2) method to evaluate the similarity of dissolution behavior between generic drugs and original research drugs, and compared the result with paddle method. The friability, weight variation and loss of mass of half-tablets were determined by friability tester and electronic balance through splitting by hand and by the cutting device respectively. RESULTS The f2 of generic drug A in 4 dissolution medium were higher than 50 and showed its similarity to original drug. While the generic drug B was not consistent with the dissolution behavior of original drug as its f2 factorswere all less than 50 in 4 dissolution. The post-segmentation weight variation, loss of mass and fragility of generic drug A and B were higher than those of the original drug. CONCLUSION The dissolution curve of oxcarbazepine half tablet preparation measured by the reciprocating cylinder method has good discrimination compared to the paddle method, and there is still a certain gap in the quality control of the generic drug in different doses compared to the original research drug.