Objective: To investigate how parental divorce impacts psychological abuse and neglect among middle and high school students, so as to provide evidence for the development of family intervention strategies for mental health promotion. Methods: A stratified random cluster sampling method was employed to select students from 23 middle and high schools in Nanchong, Neijiang, and Luzhou. Online questionnaires utilizing the General Data Questionnaire and the Child Psychological Abuse and Neglect Scale (CPANS) were administered. Propensity score matching (PSM) was used to compare individual characteristics between parent divorce and the control groups. The χ 2 test was then employed to analyze differences in psychological abuse and neglect across variables, with Logistic regression used to treat psychological abuse and neglect as dependent variables. Results: After PSM, there were 1 898 cases in both parent divorce and control groups. There was no significant difference in gender composition between the two groups ( χ 2=0.03, P >0.05). Compared to the control group, after controlling for various factors including gender, phase of studying, parental education, whether to live in school, and long term caregivers of the student, the risk of experiencing psychological abuse ( OR=1.43, 95%CI =1.26-1.63) and neglect ( OR=1.53, 95%CI =1.33-1.75) was significantly higher in parentdivorce group ( P <0.05). Conclusions Parental divorce significantly impacts psychological abuse and neglect experienced by middle and high school students. Therefore, support and intervention efforts should be intensified for students from divorced or unstable marriage families.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective:To investigate the safety and efficacy of pseudomonas aeruginosa Injection (PAI) in the treatment of coeliac leakage after cervical lymph node dissection for robotic thyroid cancer.Methods:Retrospective analysis of 1262 patients who underwent robotic thyroid surgery at the 960th Hospital of the People’s Liberation Army from Jan. 2021 to Aug. 2023 was made. Postoperative celiac leakage happened in 28 patients. The control and injection groups were divided according to whether pseudomonas aeruginosa injection was used or not. In the control group, there were 4 males and 11 females out of 15 patients, with an average age of (46.20±9.02) years old, and the treatment methods of low-fat diet, negative pressure suction, and pressure bandage were used. In the injection group, there were 7 males and 6 females among 13 patients, with an average age of (41.00±8.87) years. They were treated with low-fat diet, negative pressure suction, pressure bandage, and PAI .The number of lymph node dissection, total drainage volume, peak drainage volume, days of hospitalization and the rate of decline in drainage volume within 24 h after the use of PAI in the injection group, post-injection temperature, number of injections, and post-injection extubation time were statistically analyzed in both groups. Independent samples t test, Mann-Whitney U test, χ2 test or Fisher’s exact test were used for comparison between groups. Results:There was no statistically significant difference in age, gender, extent of thyroidectomy, highest daily drainage volume, and total drainage volume between the two groups ( P>0.05). The difference in the number of lymph node dissection (49.15±23.05 vs. 30.80±11.76, P=0.012) and hospitalization time (11.77±4.64 vs. 16.40±6.42, P=0.041) between the injection group and the control group was statistically significant. After the use of pseudomonas aeruginosa injection, the draining fluid decreased from the previous day (69.56± 20.82) % in the injection group; Twelve patients were successfully extubated after one injection of pseudomonas aeruginosa injection, and one patient was successfully extubated after two injections; the mean time to extubation after injection was (3.85±1.28) days; 76.9% patients (10/13) had fever symptoms within 48 h with body temperature (38.05±0.89) ℃ after injection, body temperature returned to normal after symptomatic treatment,and no other adverse reactions occurred except fever. Conclusion:Pseudomonas aeruginosa injection is safe and effective in the treatment of celiac leakage after cervical lymph node dissection for robotic thyroid cancer, effectively reducing cervical drainage and shortening hospitalization days.

BACKGROUND:Studies have found that nicotine can activate the dopamine system,slowing the progression of Parkinson's disease,but the specific mechanism is still unclear.Research on the neuroprotective mechanism of nicotine in animal models of Parkinson's disease is lacking. OBJECTIVE:To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson's disease in mice. METHODS:Twenty-eight C57BL/6 mice were randomly divided into vehicle group,rotenone group,autophagy agonist group and nicotine group,with seven mice in each group.Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice,and the autophagy agonist(rapamycin)or nicotine was given before modeling.The spatial exploration function of the mice was observed by open field test.Western blot and Q-PCR were used to detect the expression of α-synuclein,autophagy related factors Beclin-1 and P62,and apoptosis-related factors Bax,Bcl-2 and Cleaved-caspase3 in the nigra of each group.The deposition of mitochondria,autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy.The survival of neurons was observed by Nissl staining.The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION:The open field test showed that the distance,average speed and time of movement were reduced in the rotenone group compared with the solvent group.Compared with the rotenone group,the exercise distance,average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group(P＜0.05).The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group.Compared with the rotenone group,the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group.Western blot and Q-PCR results showed that compared with the solvent group,the expressions of α-synuclein and P62 in the rotenone group were increased,while Beclin-1 expression was decreased(P＜0.05);compared with the rotenone group,the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group,and the expression of Beclin-1 increased(P＜0.05).Compared with the solvent group,the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group(P＜0.05);compared with the rothenone group,the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups(P＜0.05).To conclude,nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson's disease mouse models by improving autophagy dysfunction and reducing apoptosis.

Objective To explore the impact of the three-level assistance model based on the narrative nursing theory on the mental health status of medical staff.Methods 140 medical staff working in a third class hospital in Xiangyang City were selected as the research object.The three-level assistance model based on narrative nursing theory was used to intervene them from September 2021 to July 2022.The symptom self-assessment scales before and after the intervention were compared.Results Before the intervention,the total score of SCL-90(156.37±32.56)points and the scores of various symptom factors of medical staff were higher;After the intervention,the total score of SCL-90(133.35±43.48)points and the scores of various symptom factors were lower than those before the intervention and the difference was statistically significant(P<0.05).Conclusion The three-level assistance model based on narrative nursing theory can reduce the total score of SCL-90 and the scores of various symptom factors,improve the mental health status and mental health level.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To evaluate the change of energy metabolism during cisplatin-induced acute kidney injury.Methods Adult CD-1 male mice were intraperitoneally injected with a single dose of cisplatin (20 mg/kg), and renal function and renal tissue pathology were tested;gene expression was analyzed and signaling pathways were en-riched in cisplatin-treated renal tubular epithelial cells using transcriptome; the contents of renal glycolysis and a-mino acid metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) .Re-sults Serum urea nitrogen and blood creatinine significantly increased in cisplatin-treated mice.Pathological his-tology observed swelling and shedding of renal tubular epithelial cells.Transcriptome analysis revealed that 2632 genes were upregulated and 2799 genes were downregulated in cisplatin-treated HK-2 cells.GO and KEGG analy-sis showed that differential genes were enriched in energy metabolism.The GSEA analysis results showed that cispl-atin caused an upregulation of the oxidative phosphorylation pathway and a downregulation of the glycolysis pathway in renal tubular epithelial cells, further KEGG analysis demonstrated that cisplatin caused changes in the expression of amino acid genes in renal cells.Metabolomics showed that the contents of glycolytic intermediates and several a-mino acids were altered in the kidney of cisplatin-treated mice.Conclusion Cisplatin-induced acute renal injury is accompanied by modification in renal tubular cell glycolysis and amino acid metabolism.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.