Objective:To investigate the clinical value of individualized therapy based on the molecular target detection to improve the prognosis of children with refractory or relapsed malignant solid tumor.Methods:The clinical data of children who were diagnosed with malignant solid tumors between September 1 st 2012 and March 31 th 2019 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were enrolled.The chemosensitivity of commonly used antitumor drugs was investigated and analyzed by detecting the target gene or protein with immunohistochemistry, real time fluorescence quantitative polymerase chain reaction and next generation sequencing.The tumor response rates and survival rates of patients with refractory or relapsed malignant solid tumors in individualized therapy group were compared with that in palliative therapy group. Results:The chemosensitivity of commonly used antitumor drugs was investigated in 172 patients.When other tissues were collected after neoadjuvant chemotherapy in 159 cases, the tumor tissues were collected before primary chemotherapy in 13 cases.The results of chemosensitivity in whole patients suggested the natural resistance of tumor cells to commonly used antitumor drugs except Methotrexate.The resis-tance rate of anthracyclines increased from 41.9% to 78.3% after chemotherapy ( P<0.05). Both the median survival time [(6.0±4.6) months] and the expected 2-year survival rate [(39.2±22.6)%] of individualized therapy group were higher than the median survival time [(1.5±1.4) months] and the expected 2-year survival rate (0) of palliative therapy group in 29 children developing primary and refractory disease (all P<0.05). The median survival time [(6.0±2.3) months] of the individualized therapy group was higher than that [(1.0±0.5) months] of palliative therapy group in 29 children suffering from relapsed disease ( P<0.05). However, there was no significant diffe-rence of expected 2-year survival rate between the 2 groups ( P=0.292). Conclusions:An attempt may be made to expand the application scope of Methotrexate in therapy of children suffering from malignant solid tumors.Individualized therapy based on the target detection of chemosensitivity can increase the overall survival rate of patients with refractory malignant solid tumors.However, treatment methods for children with recurrence disease still need further researches.

[Objective] To investigate the characteristics of PD-1/PD-L1 expressed on T cell and bladder cancer cell and clinical significance.[Methods] 64 patients with primary bladder cancer were into experiment group and 10 normal people were into control group.Peripheral bloods were used to test the PD-1 expressed on CD8+ T lymphocytes by flow cytometry.Immunohistochemistry staining was used to detect the PD-L1 expression in tumor and normal specimen.[Results] PD-1 expressed on CD8+T lymphocytes was (2.25 ± 0.60)％ in experiment group and (0.68 ± 0.17)％ in control group,respectively (P ＜ 0.001).And the PD-1 expression on T cell in invasive bladder cancer patient was significant higher than superficial bladder cancer patients [(3.04 ± 0.46)％ vs (0.68± 0.17)％,P ＜ 0.001].The expression of PD-L1 in experiment group was higher than control group,(26/64 vs 0/15,P ＜ 0.001).But there was no different between invasive and superficial bladder cancer patients,(41.3％ vs 38.8％,P ＞ 0.01).[Conclusions] Expression of negative stimulatory molecule PD-1 in CD8+T lymphocytes of peripheral blood is significantly correlated with bladder cancer advanced.Bladder cancer cell was strongly expressed PD-L1,and this expression is not related to cancer advanced.

Objective:To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI).Methods:A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis.Results:During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH 2O, 1 cmH 2O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH 2O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH 2O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ 2 = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment. Conclusion:Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.

Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P＜0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.

Objective: To preliminarily develop Health Literacy Scale for pupils, providing a tool for dynamic monitoring and related health literacy research among pupils. Methods: Through policy and literature review, the health literacy evaluation index system of pupils was established. Through two rounds of expert consultation, the evaluation index system and scale item pool of three levels in primary school were formed, and "Evaluation Scale 1.0" was developed. Through two panel discussions, health education experts, teachers and students were invited to provide advices on the content, expression and structure of scale 1.0, turning it into "Evaluation Scale 2.0", and completing the preliminary development of the scale. Results: The health literacy assessment index system of primary school students includes three levels，including level-1 was Grade 1-2, level-2 was Grade 3-4,level-3 was Grade 5-6, covering two level indexes. The scale for primary school students contained five horizontal dimensions and four vertical dimensions. In the Delphi consultation, the response rate was 100%, and the authority coefficient was 0.85. After item selection and modification, the final version of level-1, level-2 and level-3 scales contained 36, 44 and 50 items respectively. Conclusion The development of Health Literacy Evaluation Scale for pupils has high applicability and practical value.

Objective:To investigate the combined effect of noise and hand-transmitted vibration on noise-induced hearing loss (NIHL) in the automobile manufacturing industry.Methods:From September 2018 to January 2019, cluster sampling was used to select 998 workers in an automobile factory as study subjects, among whom 352 workers exposed to noise alone were enrolled as noise group, 342 workers exposed to noise and hand-transmitted vibration were enrolled as combined effect group, and 304 workers without exposure to occupational hazardous factors were enrolled as control group. A questionnaire survey and pure tone audiometry were performed for all study subjects. An analysis of variance was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; a ordinal polytomous logistic regression analysis was used to investigate the influencing factors for NIHL (with 0.05 as the inclusion criteria and 0.10 as the exclusion criteria for independent variables) .Results:There was a significant difference in L Aeq, 8 h between groups ( P<0.05) ; the noise group and the combined effect group had a significantly higher L Aeq, 8 h than the control group ( P<0.05) , while there was no significant difference in L Aeq, 8 h between the noise group and the combined effect group ( P>0.05) . The control group had a significantly lower detection rate of hearing loss than the noise group and the combined effect group ( P<0.0125) , and the combined effect group had a significantly higher detection rate of hearing loss than the noise group ( P<0.0125) . The ordinal polytomous logistic regression analysis showed that after adjustment for confounding factors such as age, working years, sex, smoking, and drinking, both noise exposure and exposure to both noise and hand-transmitted vibration had an influence on workers' hearing ( P<0.05) , and the workers exposed to both noise and hand-transmitted vibration had a higher risk of hearing loss than those exposed to noise alone. Conclusion:There may be a combined effect of noise and hand-transmitted vibration in the automobile manufacturing industry, which can increase the risk of NIHL in workers.

Objective:To investigate the combined effect of noise and hand-transmitted vibration on noise-induced hearing loss (NIHL) in the automobile manufacturing industry.Methods:From September 2018 to January 2019, cluster sampling was used to select 998 workers in an automobile factory as study subjects, among whom 352 workers exposed to noise alone were enrolled as noise group, 342 workers exposed to noise and hand-transmitted vibration were enrolled as combined effect group, and 304 workers without exposure to occupational hazardous factors were enrolled as control group. A questionnaire survey and pure tone audiometry were performed for all study subjects. An analysis of variance was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; a ordinal polytomous logistic regression analysis was used to investigate the influencing factors for NIHL (with 0.05 as the inclusion criteria and 0.10 as the exclusion criteria for independent variables) .Results:There was a significant difference in L Aeq, 8 h between groups ( P<0.05) ; the noise group and the combined effect group had a significantly higher L Aeq, 8 h than the control group ( P<0.05) , while there was no significant difference in L Aeq, 8 h between the noise group and the combined effect group ( P>0.05) . The control group had a significantly lower detection rate of hearing loss than the noise group and the combined effect group ( P<0.0125) , and the combined effect group had a significantly higher detection rate of hearing loss than the noise group ( P<0.0125) . The ordinal polytomous logistic regression analysis showed that after adjustment for confounding factors such as age, working years, sex, smoking, and drinking, both noise exposure and exposure to both noise and hand-transmitted vibration had an influence on workers' hearing ( P<0.05) , and the workers exposed to both noise and hand-transmitted vibration had a higher risk of hearing loss than those exposed to noise alone. Conclusion:There may be a combined effect of noise and hand-transmitted vibration in the automobile manufacturing industry, which can increase the risk of NIHL in workers.

Objective To investigate the clinicopathological features and key points of diagnosis and treatment of malignant perivascular epithelioid cell tumor(PEComa)to increase awareness of the disease.Methods The clinicopathological data of 2 patients with malignant PEComa treated in our hospital were retrospectively analyzed,and relevant literatures were reviewed.Results Both patients were male,aged 53 and 16 years,respectively.The sites of occurrence were in the retroperitoneum and pelvis,respectively.Both tumors were resected surgically,and the diagnosis was confirmed with postoperative pathology.Under the microscope,the tumor tissue of one patient was mainly composed of smooth muscle-like cells,and that of the other patient was composed of epithelioid cells,both showing pathological mitotic images and expressing HMB45,Melan-A,SMA and CD34,no tumor recurrence or metastasis was observed during the follow-up.The literatures collected involved 15 patients with retroperitoneal or pelvic PEComa,including 3 males and 12 females,of which 9 were malignant.The clinical manifestations were abdominal pain,bloating,or lower back pain.Some cases were detected during physical examinations.Conclusion Malignant PEComa is difficult to be diagnosed before surgery and easy to be misdiagnosed.The confirmed diagnosis depends on the postoperative pathological results.The preferred treatment is complete resection of tumor.Long-term follow-up is needed.

Objective To explore the risk factors that affect the outcome of testicular torsion in patients with testicular resection,to provide ideas for clinical management.Methods The clinical data of 117 patients with testicular torsion treated in our hospital during Jan.1,2012 and Mar.1,2023 were retrospectively analyzed,43 of whom underwent testicular detorsion and orchidopexy,and 74 underwent orchiectomy.The correlation between preoperative inflammatory and coagulation-related indicators,testicular torsion angle,TWIST score and orchiectomy was analyzed with univariate analysis.The independent risk factors for testicular torsion patients with testicular resection as the outcome were analyzed with binary logistic regression.The predictive value of each factor for orchiectomy was assessed with receiver operating characteristic(ROC)curve.Results Binary logistic regression analysis indicated that long duration of onset(OR=1.841,P=0.036),large torsion angle(OR=1.005,P=0.016),high TWIST score(OR=2.225,P=0.003)and elevated FIB level(OR=2.489,P=0.049)were independent risk factors for testicular torsion patients with testicular resection as the outcome.ROC curve analysis showed that the best cut-off value of the above 4 factors to predict orchiectomy were 1.75 days,225°,3.5 and 3.155 g/L;the area under the ROC curve(AUC)were 0.893,0.718,0.812 and 0.770,respectively.Conclusion The duration of onset,torsion angle,TWIST score,and FIB level are independent risk factors for testicular torsion patients with testicular resection as the outcome,and these indicators have certain predictive value.

Objective:To retrospectively analyze the screening results for genetic metabolic diseases among newborns from Changsha in order to determine the prevalence of single diseases and their mutational spectrum.Methods:352 449 neonates born from January 2016 to December 2021 in Changsha were subjected to tandem mass spectrometry. Suspected cases were further analyzed by biochemical and genetic testing.Results:Among the 352 449 newborns, 6 170 were positive for the screening, which yielded a positive rate of 1.75%. 5 437 cases were recalled, and 92 were confirmed, with the overall prevalence being 1∶3 831 and positive predictive value of 1.69%. Eighteen genetic metabolic diseases were detected among the 92 children, including 33 amino acid metabolic disorder, among which 20 were phenylalanine hydroxylase deficiency (60.60%). 17 cases had organic acid metabolic disorders, among which 4 were 2-methyl-dehydrogenase deficiency (23.50%). 42 had fatty acid metabolic disorders, among which 27 (64.30%) were primary carnitine deficiency and 12 were short-chain acyl-CoA dehydrogenase deficiency (28.60%). In total 90 genetic variants were identified, with the most common ones including c. 51C>G, c. 1400C>G, c. 760C>T, c. 1031A>G and c. 1165A>G.Conclusion:The common neonatal genetic metabolic diseases in Changsha include primary carnitine deficiency, phenylalanine hydroxylase deficiency and short-chain acyl-CoA dehydrogenase deficiency. The preliminary delineation of mutational spectrum for genetic metabolic diseases in Changsha can facilitate early diagnosis and intervention, so as to improve the quality of newborn population.