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.

This paper reviews the influencing factors and intervention of post-traumatic growth of breast cancer patients. The influencing factors include demographic factors, disease treatment related factors, intimate relationships, psychological resilience, rumination, cognitive evaluation and so on. Intervention measures involve conducting group psychotherapy, enhancing positive motivational effects between partners, carrying out emotional cognitive training and exercise therapy. In summary, this paper aims to provide ideas for actively implementing interventions for post-traumatic growth in clinical nursing.

Abstract Deviant behaviors among adolescents is widespread and have substantial impacts on family and society. Increasing evidence has shown that adolescents who experienced traumatic stress events and suffered from post traumatic stress disorder are at significantly higher risk of deviant behaviors than their healthy peers and have their personal lives negatively affected. In this review, the effect of PTSD on deviant behaviors in adolescents is summarized, in which adolescent deviant behaviors are mainly classified into extroverted, introverted, and academic deviant behavior, as well as deviant habits. Meanwhile, aims to explore the neural mechanism linking PTSD and adolescent deviant behaviors, and to provide suggestions for intervention of deviant behaviors.

Dysregulated crosstalk between different signaling pathways contributes to tumor development, including resistance to cancer therapy. In the present study, we found that the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase (ERK) signaling. In particular, the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling pathways. Furthermore, the combination of the two inhibitors resulted in a reduced tumor burden in mice. Our evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC) cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.

Objective:To establish an index system of population based SARS-CoV-2 nucleic acid screening, and provide reference to determine the screening coverage appropriately.Methods:The literature review and brain storming sessions were used to develop the basic frame and index system of population based SARS-CoV-2 nucleic acid screening. Based on Delphi method and Analytic Hierarchy Process, 21 domestic experts were selected for two rounds of consultation to determine the index system of population based SARS-CoV-2 nucleic acid screening and its weight.Results:The positive indexes of experts in two rounds of consultations were both 100%. The experts' authority coefficients ( Cr) were 0.88±0.08 and 0.89±0.07, respectively. And the range of coefficient of variation ( CV) were (0.08, 0.24), (0.09, 0.25). The Kendall's W coordination coefficients were 0.34 and 0.22 respectively, which were statistically significant. The index system of population based SARS-CoV-2 nucleic acid screening was established, which had 4 first-level indexes, 11 second-level indexes and 58 third-level indexes. Besides, the weight of each index was determined. Conclusion:The index system of population based SARS-CoV-2 nucleic acid screening has been established, which can provide scientific reference for the health administration to determine the coverage of population based SARS-CoV-2 nucleic acid screening when local COVID-19 epidemic occurs.

Objective: To study the role of corticotropin-releasing hormone (CRH) system in locus ceruleus (LC) in irritable bowel syndrome (IBS) and to explore its molecular mechanism. Methods: The IBS rat was established by maternal separation following with postnatal stress. The tissues sample of LC was obtained by micropunched nuclei. The expression of c-Fos, CRH and its receptors including corticotropin-releasing hormone receptor (CRHR) 1 and CRHR2 of rats’ LC tissues of control group and IBS group was detected by quantitative polymerase chain reaction(PCR). The expression of DNA methyltransferase (DNTM) 1, DNMT3a and DNMT3b at the mRNA level were also measured. In addition, the expression of histone methyltransferase ASH2-like protein (ASH2L) and SET and MYND domain containing 2 (SMYD2) was determined by Western blotting. T test was used for statistical analysis. Results: The rectal pneumatic pressure of IBS group was lower than that of control group ((69.82±5.47) mmHg vs. (86.86±5.98) mmHg; 1 mmHg=0.133 kPa), however compared with that of control group, the expression of c-Fos at the mRNA level increased (2.11±0.44 vs.1.00±0.19), and the differences were statistically significant (t=6.215 and 2.321, P<0.01 and 0.05). In addition, compared with that of control group, the expression of CRH at the mRNA level increased (1.99±0.35 vs.1.00±0.13), and the difference was statistically significant (t= 2.797, P<0.05). Compared with that of control group, the expression of SMYD2 at the protein level up-regulated (1.04±0.21 vs. 0.61±0.12), and the difference was statistically significant (t=4.451, P<0.01). However, there were no statistically significant differences in the expression of CRHR-1, CRHR2, DNMT1, DNMT3a, DNMT3b at the mRNA level, and the expression of ASH2L between IBS group and control group (0.96±0.13 vs. 1.00±0.26, 1.35±0.63 vs. 1.00±0.43, 1.40±0.61 vs.1.00±0.19, 1.39±0.58 vs. 1.00±0.21, 1.45±0.71vs.1.00±0.39 and 0.80±0.19 vs. 1.05±0.26, respectively; all P>0.05). Conclusions Maternal separation combined with postnatal stress affect the transcription of Crh gene in LC and cause the activation of the stress regulation network CRH and norepinephrine system, resulting in the increase of the visceral sensitivity of rats. The abnormal transcription of Crh gene may be related with SMYD2-mediated histone H3K36 methylation, but not related with the modification of DNA methylation.

Objective:To understand the prevalence and epidemiological characteristics of glaucoma among people over 40 years old in rural areas of Chongqing.Methods:From August to October 2018, a stratified cluster random sampling method was used to investigate the cases of glaucoma among people over 40 years old in a rural population of the Rongchang and Qijiang Districts in Chongqing.The subjects had been living in the local area for over ten years.Basic information for each patient, including gender and age was documented, and their visual acuity and intraocular pressure were routinely measured.The Van Herick method was used to evaluate the depth of the central and peripheral anterior chamber, a preset lens was used to examine the fundus, and the cup to disc ratio(C/D) of the optic disc was emphasized.All suspected glaucoma patients underwent further standard glaucoma examinations.This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Army Medical University.Results:A total of 4 680 people were identified, and 4 073 respondents participated in the survey, and the response rate was 87%.The prevalence of glaucoma was 1.72% (70/4 073). There were no significant differences in the prevalence of primary angle-closure glaucoma (PACG) and primary open angle glaucoma (POAG) between different genders ( χ2=0.042, P=0.837; χ2=2.838, P=0.092). The prevalence of glaucoma in people over 70 years old was 2.5%, significantly higher than that in other age groups.In patients with glaucoma, the rate of visual impairment was 68.57%(48/70), and the rate of blindness was 47.14%(33/70). There was no significant difference in the incidence of low vision between different types of glaucoma ( χ2=2.785, P=0.248), but there was a significant difference in the rate of blindness ( χ2=10.668, P=0.005). The highest rate of blindness was found in secondary glaucoma.The detection rate of intraocular pressure, anterior chamber depth and C/D was statistically significant ( χ2=43.325, P<0.001), and the positive rate of C/D was the highest.When the factors of intraocular pressure, and C/D were considered jointly, the detection rate of glaucoma could be increased to 55.88%. Conclusions:The prevalence of glaucoma is 1.72% among people over 40 years old in rural areas of Chongqing, the prevalence of PACG is lower than previously recorded, but the proportion of glaucoma-induced visual impairment is higher.In field screening, the morphological examination of the fundus optic nerve is very important for the diagnosis of glaucoma.

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

Objective:To explore a new way of pharmaceutical service mode for disease treatment. Methods:Clinical pharmacists actively participated in the pharmaceutical care for a patient with mixed liver injury, and provided clinical pharmaceutical services through the adverse reaction analysis,etiological mechanisms exploration,therapeutic drugs selection and risk factors prevention. Re-sults:Clinical pharmacists cooperating closely with physicians helped to identify problems in time,and then the medication analysis in the fields of drug selection, dose determination, efficacy evaluation and indicators detection was performed, so that the strategies on medicine treatment could be adjusted timely as the disease progressed. With the gradual recovery of liver function, the patient dis-charged after the conditions were improved. Conclusion:By participating in pharmaceutical practice,clinical pharmacists can provide clinical pharmaceutical service,which is helpful to safety improvement and efficiency of drug administration. It is also an effective way to enhance the learning ability of pharmacists,and cultivate their clinical thinking and practice capacity.

Objective To study the clinicopathologic features,immunophenotype,diagnosis and differential diagnosis,prognosis and treatment of solid papillary carcinoma(SPC)of breast.Methods A retrospective study was performed to analyse the clinicalpathologic features and immunophenotype of 52 case of SPC,with or without invasion. The cytokeratins(CK),myoepithelial markers,neuroendocrine markers,proliferation marker Ki -67,estrogen receptor (ER),progesterone receptor(PR),HER2,ect were detected by immunohistochemical staining,and HER2 was detected by FISH.All patients were followed up.Results All the patients were females with a mean age of (66.76 ±10.19)years. The incidence of SPC among all the breast cancers in this department was 0.99%.The presenting symptoms was a painless mass with or without nipple discharge in the central of breast.All of them accepted surgical resection,13 cases were administrated with chemotherapy after surgery,6 cases were radiotherapy.Metastasis was observed four in 34 cases who had undergone axillar lymph node dissection.General observation tumor was substantive and nodular lesions,may be accompanied by cyst formation,microscopy tumor for swelling,substantive nodules within only fine fiber vascular axis,and lacked obvious nipples and screen structure.The cells were lack of atypia,adhesive in cells nest,35 patients were accompanied with mucus secretion.Immunohistochemical study show that the tumor cells experssed CK8 /18,ER and PR,but not basal cell cytokertin CK5 /6 and 34βE12.Positivity for CK5 /6,34βE12 and P63 were 5.78%, 9.62% and 7.69% in the myoepithelial layers of axis of papillary,and were 21.15%,38.46% and 19.23% in cell nests and tumor peripheral myoepithelial,respectively.Positivity for CgA,Syn,NSE,CD56 were 82.69%,88.46%, 94.23% and 90.38%,respectively.The staining of HER2 oncoprotein was most negative,and 23 cases of FISH detection were all negative.The average positive index of Ki -67 was 4.28%.47 cases received follow -up of patients(90.38%),only 1 case death,1 case recurrence the rest were no tumor recurrence or metastasis,disease -free survival.Conclusion SPC of breast,a rare pathologic type,usually occurs in old females.The diagnosis depends on pathological characteristics and its unique immune phenotypic characteristics,is closely associated with mucinous carcinoma and neuroendocrine carcinoma,and the treatment is given priority tosurgery with a relatively inert biological behaviour.