OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

OBJECTIVE To compare the ability of ultra-high-resolution CT(U-HRCT)and multi-slice spiral CT(MSCT)to display key vocal transmission structures in the middle ear.METHODS Subjects with normal middle ear structures who underwent 0.1 mm layer thickness U-HRCT and 0.625 mm layer thickness MSCT scans at the same time in Beijing Friendship Hospital affiliated to Capital Medical University from December 2019 to August 2024 were retrospectively enrolled.Two experienced head and neck radiologists reconstruct standard transsectional,coronal images based on the thinnest layer thickness.According to the 5-point method,16 key sound transmission structures of the middle ear,including malleus,incus and stapes,as well as joints,ligaments and tendons,were evaluated for image quality scoring.The standard deviation(SD)value,signal noise ratio(SNR),and contrast noise ratio(CNR)of bone in the malleus region and intratympanic gas were measured and calculated on the two examination images.RESULTS Thirty patients(47 sides)with normal middle ear structure were included,including 18 males and 12 females.The two physicians compared the results of U-HRCT in showing malleus head,malleus neck,malleus handle,incus body,long process,and short process,5 points accounted for 100%,and the 5-point scores of incudomalleolar joint space,incudostapedial joint space,stapes footplate and annular ligament were 100%,98.29%,75.83%and 77.83%,respectively,which were significantly higher than those of MSCT(P<0.001).In addition,U-HRCT showed higher scores for lenticular process,stapes head,anterior arch of stapes,posterior arch of stapes,annular ligament,stapes muscle,and tendo musculi tensoris tympani than MSCT(P<0.001),and the lenticular process showed a 100%display rate.There was no significant difference in the SNR between the two groups(P>0.05),but the SD value of the malleus in U-HRCT was 161.6±36.4,which was significantly lower than that in MSCT(297.8±128.1),and the difference was statistically significant(P<0.001).CONCLUSION U-HRCT can clearly visualize the key sound transmission structures of the middle ear,and its visualization ability is significantly better than that of MSCT.

Objective To explore the predictive value of the blood uric acid/creatinine ratio(SUA/Cr)and the Osteoporosis Self-Assessment Tool for Asians(OSTA)for osteoporosis(OP)in middle-aged,older,and elderly adult Tibetan populations in Xizang.Methods A total of 1058 middle-aged and older adult ethnic Tibetans who underwent physical examination in Xizang between June 2020 and December 2023 were selected for the study.Fasting venous blood samples were collected for laboratory analysis.The bone mineral density(BMD)of the radius of the participants was measured using dual-energy X-ray absorptiometry.Based on the BMD measurement results and OP diagnostic criteria,participants were divided into the OP group(n=759)and the non-OP group(n=299).Multivariate logistic stepwise regression analysis was used to further identify independent predictors associated with OP risk in the middle-aged and older adult Tibetan population.The predictive value of SUA/Cr and OSTA for OP was evaluated using the receiver operating characteristic(ROC)curve.Results 1)The OP prevalence among the middle-aged and older adult Tibetan populations was 28.3％(299 people),including 209 females(69.9％)and 90 males(30.1％).Significant differences between the two groups were found in terms of age(OP group:62[54,69]vs non-OP group:56[51,62]),SUA/Cr(OP group:6.86[5.06,10.23]vs non-OP group:5.36[4.36,6.52]),and OSTA(OP group:[-1.27±3.06]vs non-OP group:[1.25±2.68])(P＜0.05).2)SUA/Cr(OR:1.592,95％CI:1.469-1.726)was identified as a risk factor for OP,while OSTA(OR:0.706,95％CI:0.662-0.752)was a protective factor for OP(P＜0.05).3)For gender-based group analysis,the combined use of SUA/Cr and OSTA showed better diagnostic performance for OP,with AUCs of 0.807(95％CI:0.751-0.863)for males and 0.820(95％CI:0.782-0.857)for females.For age-based group analysis,the combined diagnosis of OP using SUA/Cr and OSTA provided the best performance,with the optimal cutoff value increasing with age.4)In the middle-aged group and the older adult male group,the combined use of SUA/Cr and OSTA for OP diagnosis was more effective than using SUA/Cr or OSTA alone(P＜0.001).In the elderly adult male group,the AUC for SUA/Cr was 0.954(95％CI:0.858-1.000),with a sensitivity of 88.9％and specificity of 100.0％,indicating excellent predictive performance.In females,the diagnostic effectiveness of OSTA and the combined use of SUA/Cr and OSTA increased with age across different age groups.Conclusion The predictive performance of SUA/Cr and OSTA for OP varies across different sex and age groups in the Tibetan population.Both SUA/Cr and OSTA can be used to predict OP in middle-aged and older adult Tibetan populations,with the combined use of SUA/Cr and OSTA providing better predictive performance.

Objective:To analyze the occupational disease hazards in stone processing enterprises in Weihai City to provide scientific basis for occupational disease prevention.Methods:From January 2021 to December 2022, 107 stone processing enterprises in Weihai City were selected to collect the detection status of occupational hazard factors in the workplace through on-site investigation and on-site monitoring of occupational hazard factors. The diagnostic reports on occupational diseases and suspected occupational diseases of 780 workers were collected through the Occupational Diseases and Hazard Factors Monitoring Information System of the Chinese Center for Disease Control and Prevention, the occupational health monitoring files of the occupational health examination institutions and the information data of the occupational disease diagnosis institutions. The differences between the measurement data were analyzed by Chi-square test or Fisher exact probability method.Results:107 stone processing enterprises were mainly focused on granite processing, and the average free silica content in granite was 32.92% (12.78%-47.84%). The over-standard rate of silica dust was 0.31% (6/1920), and the over-standard rate of noise was 86.20% (1324/1536). Among them, the noise intensity of cutting position was the highest[120.5 dB (A) ]. The over-standard rates of noise in cutting, water grinding, dry grinding (polishing) and material preparation (forklift transportation) were 98.05%, 89.55%, 70.00% and 42.62%, respectively, and the differences were statistically significant ( P<0.05). Among 780 workers, 31 cases (3.97%) of suspected silicosis were detected, and 13 cases (1.67%) were diagnosed with silicosis. 51 cases (6.54%) of suspected occupational noise deafness were detected, and 11 cases (1.41%) were diagnosed with occupational noise deafness. Conclusion:Silicon dust and noise in some positions of stone processing enterprises in Weihai City exceed the standard, and supervision should be strengthened, prevention and control measures should be implemented to protect the occupational health of workers.

[Objective] To analyze the correlation of serum creatinine (Cr), hemoglobin (HGB) and body mass index (BMI) with osteoporosis in middle-aged and elderly Tibetan residents in Xizang and its predictive value for osteoporosis. [Methods] Between November 2021 and August 2023, using multistage random cluster sampling method information on demographics, we collected blood indices and bone mineral density from 564 middle-aged and elderly Tibetan residents in Ali (Pulan, Zada, Ritu, and Rezhe counties), Nagchu (Nagchu, Nyima, Amdo, Shuanghu, and Bango counties), Shannan (Lunzi county), and Lhasa (Nimu county), Tibetan regions. They were divided into osteoporosis group (90 cases) and non-osteoporosis group (474 cases) according to whether they suffered from osteoporosis or not. Pearson correlation method was used to analyze the correlation between bone mineral density (BMD) and each variable. Binary Logistic regression was used to analyze the related influencing factors of osteoporosis in middle-aged and elderly Tibetan residents, and the regression equation model of predicting the risk factors of osteoporosis was constructed. The fitting degree of the model was tested by Hosmer-Lemeshow test model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum Cr, HGB and BMI combined tests on osteoporosis in middle-aged and elderly Tibetan residents in Xizang. [Results] The prevalence of osteoporosis was higher in females than in males. Among the osteoporosis group, height and weight, alanine aminotransferase, glutamine aminotransferase, urea nitrogen, uric acid, total cholesterol, triglyceride, low-density lipoprotein cholesterol, homocysteine, serum Cr, HGB and BMI were significantly lower (P<0.05). Correlation analysis showed that age was negatively correlated with BMD, while body weight, serum Cr, HGB and BMI were positively correlated with BMD (P<0.05). Multivariate binary Logistic results showed that age (OR=1.085), serum Cr (OR=0.891), BMI (OR=0.475), and HGB (OR=0.966) were the influencing factors for the occurrence of osteoporosis (P<0.05). To establish a prediction model for the risk of osteoporosis, Logit(P)=6.265+ 0.086×age + (-0.109×Cr)+ (-0.020×HGB)+ (-0.213×BMI). The area under the ROC curve was 0.932, the sensitivity was 88.9%, and the specificity was 82.5%. Hosmer-Lemeshow test model had a good fit (P=0.960). According to Logit(P) model, L score=-29.413+ (-0.404×age)+ 0.512×Cr+ 0.094×HGB+ BMI could be calculated. When L score >8.9, the patient could be diagnosed with the disease. [Conclusion] The decrease in serum Cr, HGB and BMI is a risk factor for osteoporosis in Tibetan aged residents. Age was negatively correlated with BMD, while serum Cr, HGB and BMI were positively correlated with BMD. The combined model of age, serum Cr, HGB and BMI can significantly improve the diagnostic efficiency of osteoporosis in the elderly Tibetans in Xizang.

Objective:To analyze the occupational disease hazards in stone processing enterprises in Weihai City to provide scientific basis for occupational disease prevention.Methods:From January 2021 to December 2022, 107 stone processing enterprises in Weihai City were selected to collect the detection status of occupational hazard factors in the workplace through on-site investigation and on-site monitoring of occupational hazard factors. The diagnostic reports on occupational diseases and suspected occupational diseases of 780 workers were collected through the Occupational Diseases and Hazard Factors Monitoring Information System of the Chinese Center for Disease Control and Prevention, the occupational health monitoring files of the occupational health examination institutions and the information data of the occupational disease diagnosis institutions. The differences between the measurement data were analyzed by Chi-square test or Fisher exact probability method.Results:107 stone processing enterprises were mainly focused on granite processing, and the average free silica content in granite was 32.92% (12.78%-47.84%). The over-standard rate of silica dust was 0.31% (6/1920), and the over-standard rate of noise was 86.20% (1324/1536). Among them, the noise intensity of cutting position was the highest[120.5 dB (A) ]. The over-standard rates of noise in cutting, water grinding, dry grinding (polishing) and material preparation (forklift transportation) were 98.05%, 89.55%, 70.00% and 42.62%, respectively, and the differences were statistically significant ( P<0.05). Among 780 workers, 31 cases (3.97%) of suspected silicosis were detected, and 13 cases (1.67%) were diagnosed with silicosis. 51 cases (6.54%) of suspected occupational noise deafness were detected, and 11 cases (1.41%) were diagnosed with occupational noise deafness. Conclusion:Silicon dust and noise in some positions of stone processing enterprises in Weihai City exceed the standard, and supervision should be strengthened, prevention and control measures should be implemented to protect the occupational health of workers.

Objective To investigate the expression and role of neutrophil extracellular traps(NETs)in oral squamous cell carcinoma(OSCC).Methods Immunofluorescence and immunohistochemistry were used to detect the expression of NETs in OSCC.The clinico-pathological characteristics and prognosis of patients with different NETs expression levels were analyzed.Density gradient centrifugation was used to isolate neutrophils from human peripheral blood.NETs were induced by phorbol 12-myristate 13-acetate(PMA)and co-cultured with OSCC cells.CCK-8 assay was used to detect changes in OSCC cell proliferation ability.OSCC cell migration ability was detected by Transwell cell migration assay and cell scratch assay.Western blotting(WB)assay was used to detect the effect of NETs on the index of epithelial-mesenchymal transition(EMT).Results NETs'expression in OSCC was higher than that in normal tissues(P＜0.001).The prognosis of patients with high NETs expression was worse than that of patients with low NETs expression(P＜0.05).The expression level of NETs was correlated with the clinical grade,invasion and recurrence degree of OSCC patients(P＜0.05).NETs pro-moted the proliferation and migration of Cal27 and HN6 cells(P＜0.05),and inhibited the protein expression level of epithelial marker and promoted the protein expression level of mesenchymal markers(P＜0.05),which could be reversed by the NETs inhibitor DNaseⅠ.Conclusion NETs are expressed at high levels in OSCC.NETs can promote the proliferation and migration of OSCC cells by regulating epithelial-mesenchymal transition and can affect the prognosis of OSCC patients.

Objective To investigate the effects of platelet-rich plasma-derived exosomes(PRP-Exos)on the proliferation and migration of tendon stem/progenitor cell(TSPC).Methods PRP-Exos were extracted through the combination of polymer-based precipitation and ultracentrifugation.The morphology,concentration,and particle size of PRP-Exos were identified by transmission electron microscopy and nanoparticle tracking analysis.The expression levels of surface marker proteins on PRP-Exos and platelet membrane glycoproteins were deter-mined by Western blot analysis.Rat TSPC was extracted and cultured,and the expression of surface marker mol-ecules on TSPC was detected using flow cytometry and immunofluorescence staining.The proliferation of TSPC in-fluenced by PRP-Exos was evaluated using CCK-8 assay and EdU assay.The effect of PRP-Exos on the migration of TSPC was evaluated by cell scratch assay and Transwell assay.Results The extracted PRP-Exos exhibit typi-cal saucer-like structures,with a concentration of 4.9 ×1011 particles/mL,an average particle size of(132.2±56.8)nm,and surface expression of CD9,CD63 and CD41.The extracted TSPC expressed the CD44 pro-tein.PRP-Exos can be taken up by TSPC,and after co-cultured for 48 h,concentrations of 50 and 100 μg/mL of PRP-Exos significantly promoted the proliferation of TSPC(both P＜0.001),with no statistical difference be-tween the two concentrations(P=0.283).Additionally,after co-cultured for 24 h,50 μg/mL of PRP-Exos significantly promoted the migration of TSPC(P＜0.001).Conclusion Under in vitro culture conditions,PRP-Exos significantly promote the proliferation and migration of rat TSPC.

Objective: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China. Methods: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022. Results: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464). Conclusions and Relevance: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.

ObjectiveTo explore the mechanism of Huanglian Ejiaotang in intervening in insomnia based on 5-hydroxytryptamine （5-HT） system and gut microbiota. MethodFifty-five SPF-grade SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose Huanglian Ejiaotang groups （1.925， 3.85， and 7.7 g·kg^-1）， and Estazolam group （0.1 mg·kg^-1）. Except for those in the normal group， the rats in the other five groups were subjected to sleep deprivation on a narrow platform for 12 hours daily for 21 consecutive days. After 14 days of drug intervention， the sleep， exploratory behavior， and depressive-like behavior of the rats were assessed using the pentobarbital sodium sleep synergistic test， the open field test， and the sugar preference test， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of 5-HT， 5-hydroxyindoleacetic acid （5-HIAA）， tryptophan hydroxylase （TPH）， and monoamine oxidase-A （MAO-A）. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of the 5-HT1A receptor （5-HT1AR） and 5-HT2A receptor （5-HT2AR）. Differences in gut microbiota among the groups were assessed using 16S rRNA sequencing， and the correlation between the 5-HT system and microbiota was revealed using redundancy analysis. ResultCompared with the normal group， the model group showed a prolonged sleep latency （P<0.05）， reduced sleep maintenance （P<0.01）， decreased central area activity time in the open field （P<0.01）， and reduced sugar preference rate （P<0.05）. Moreover， the model group also showed decreased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， decreased 5-HIAA/5-HT ratio （P<0.01）， downregulated mRNA expression of 5-HT1AR （P<0.01）， and upregulated mRNA expression of 5-HT2AR （P<0.05）. The proportion of Firmicutes decreased， while that of Bacteroidetes increased， leading to a decreased Firmicutes/Bacteroidetes （F/B） ratio （P<0.05）. Compared with the model group， the high-dose Huanglian Ejiaotang group exhibited a shortened sleep latency （P<0.01）， and increased sleep maintenance （P<0.01）. The low-dose Huanglian Ejiaotang group showed increased central area activity time （P<0.01） and an increased sugar preference rate （P<0.05）. The high-dose Huanglian Ejiaotang group exhibited increased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， increased 5-HIAA/5-HT ratio （P<0.05）， upregulated mRNA expression of 5-HT1AR （P<0.01）， and downregulated mRNA expression of 5-HT2AR （P<0.05）. The low-dose Huanglian Ejiaotang group displayed an increased proportion of Firmicutes and a decreased proportion of Bacteroidetes， resulting in an increased F/B ratio. At the phylum level， 5-HT， 5-HIAA， and MAO-A were positively correlated with Firmicutes and negatively correlated with Bacteroidetes. At the genus level， 5-HT， 5-HIAA， TPH， and MAO-A were negatively correlated with Prevotella and Lactobacillus and positively correlated with Blautia and Bacteroides. ConclusionHuanglian Ejiaotang can improve sleep deprivation-induced insomnia and depressive-like behavior by regulating the activity of the 5-HT system and the composition of gut microbiota.