Objective To investigate the prevailing situation concerning psychological crisis intervention abilities of college staff,and provide countermeasures and suggestions for further strengthening the psychological crisis intervention abilities of college counselors.Methods A"Questionnaire on the Structure of Psychological Crisis Intervention Ability of College Counselors,"was conducted among 120 college counselors and 240 college students from eight colleges in Shenyang.A total of 92 counselors and 199 college students'responses were collected,with an effective recovery rate of 80.83%.Results There were statistical differences between male counselors and female counselors in personality trait dimension(t=-2.156,P＜0.05).There were also statistical differences between counselors who had dealt with students'psychological crises and those who had not in terms of the knowledge(t=-2.786,P＜0.01)and ability dimen-sions(t=-2.151,P＜0.05).Statistical differences were also observed in the evaluation of counselors'crisis intervention ability between students who had experienced psychological crisis events and those who had not.Lastly,there were statistical differences in the empathy(t=-3.176,P＜0.01)and personality trait dimensions(t=-2.424,P＜0.05)between counselors'self-evaluation and students'evaluation.Conclusion At present,college counselors have improved intervention capacity in dealing with students'psychological crises,but it is still necessary to strengthen the preventive role in psychological crisis intervention.Universities need to strengthen speciali-zed training on psychological crisis intervention and provide resources and support for counselors.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To observe the protective effect of 2% taurine on corneal endothelial cells injured by benzalkonium chloride in rats. Methods Six piece of corneal endodermis and elastic layer tissue slices were prepared from 6 eyes of 3 SPF SD rats and randomly divided into three groups. The corneal endothelial cells of rats were cultured by tissue block culture for 1 day, then the control group cells were added with 2% taurine solution, while the experimental group cells were added with 2% taurine solution and 0.01% or 0.03% benzalkonium chloride solution. After 1, 2, 4, 5, 6 and 8 days of continuous culture, the growth of corneal endothelial cells in each group was observed under an inverted microscope, and the morphology of endothelial cells was observed under an optical microscope after Wright staining. Results Treated with 0.01% benzalkonium chloride and 2% taurine for 1 day, polygonal endothelial cells appeared on the edge of corneal tissue mass, and the cells were transparent. After 2 days, the number of polygonal cells increased, and there was no fusion growth between cells. After 3 days, the number of polygonal cells decreased and no mitotic signs were observed in endothelial cells. After 4 days, the endothelial nuclei were deeply stained and polygonal cells were rare. After 5 days, the number of endothelial cells decreased, and cell body shrinkage and death occurred. In the experimental group treated with 0.03% benzalammonium chloride and 2% taurine for 1 day, no endothelial cell growth was observed and the cells were sparsely-scattered. In control group, polygonal endothelial cells and a few endothelium-like polygon cells appeared at the edge of tissue blocks after 1 day. After 3 days, the number of polygonal cells at the edge of tissue blocks increased, and there was a phenomenon of gradual fusion growth. After 5 days, the number of endothelial cells increased, and the cells were mostly hexagonal. After 8 days, the endothelial cells formed large sheets, the cell bodies were hexagonal or round, and the nuclei were divided. The growth of corneal endothelial cells in the left and right eyes was uniform, and there was no significant difference in the morphology of the left and right eye endothelial cells in the 0.01% and 0.03% benzalammonium chloride treatment groups and the control group. Conclusion 2% taurine had no protective effect on corneal endothelial cells injured by benzalammonium chloride.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective:To investigate postoperative pathological diagnosis upgrade of high-grade cervical squamous intraepithelial lesions (HSIL) in postmenopausal women and its influencing factors.Methods:Clinicopathologic data of 378 post-menopausal women with HSIL who underwent cervical conization or total hysterectomy in Shanxi Bethune Hospital between January 2017 and December 2021 were retrospectively analyzed. According to whether the pathological diagnosis was upgraded after operation, they were divided into upgraded group and non-upgraded group. The clinicopathological characteristics of both groups were compared. Multivariate logistic regression was used to analyze the influencing factors of postoperative pathological upgrade.Results:Among 387 patients, 28 patients (7.2%) were postoperatively upgraded to cervical cancer. Compared with the non-upgraded group, the proportions of the following indexes in the upgraded group were higher [the proportion of HSIL detected by cervical thinprep cytologic test (TCT): 57.1% (16/28) vs. 44.6% (160/359); the proportion of HSIL detected by colposcopic impression: 89.3% (25/28) vs. 59.3% (213/359); the proportion of glandular involvement: 46.4% (13/28) vs. 24.0% (86/359); the number of lesion involvement ≥ 2: 82.1% (23/28) vs. 59.6% (214/359); the proportion of positive endocervical curettage (ECC): 64.3% (18/28) vs. 46.0% (165/359)]; and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in the proportions of patients stratified by menopausal duration, colporrhagia, gravidity frequency, reproductive frequency, human papillomavirus (HPV) 16/18 infection and multiple HPV infection (all P > 0.05). Multivariate logistic analysis found that colposcopic impression of HSIL ( OR = 6.195, 95% CI 1.432-26.804), glandular involvement ( OR = 2.468, 95% CI 1.050-5.801), and ECC positive ( OR = 3.477,95% CI 1.028-11.764) were independent risk factors for postoperatively upgraded to cancer for postmenopausal HSIL patients in women (all P < 0.05). Conclusion:For post-menopausal women, patients with colposcopic impression of HSIL, glandular involvement and ECC positive should be alert to the risk of postoperatively pathological upgrade.

Objective To investigate the inhibitory effect of anti interleukin(IL)-8 monoclonal antibodies on the growth and metastasis of cervical cancer. Methods Involved cervical cells included CaSki cells with high expression of IL-8 and SiHa cell lines with IL-8 plasmid transfected (pcDNA3.1-IL-8-SiHa). Cervical cancer animal model was established on nude mice. Boyden method was used in vitro study to observe the effects of anti IL-8 antibodies on the chemotaxis of high-expressed IL-8 cervical cancer cells. The effect of anti IL-8 antibodies on the growth of cervical cancer cells and nude mice transplantation tumor was observed by the experiment in vivo through reverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA), TUNEL method. Cell line (CaSki and pcDNA3.1-IL-8-SiHa) modeled nude mice were divided into 5 groups with 5 animals in each group. The blank control group (group Ⅰ) was given the equal volume of phosphate buffer solution (PBS). Negative control group (group Ⅱ) was injected with IgG at the same volume of IgG. Treatment group (group Ⅲ) was injected with anti IL-8 antibodies at dose of 100 μg for once and intervals for once 2 days. Treatment group (group Ⅳ) was injected with anti IL-8 antibodies at dose of 500 μg for once and intervals for once 3 days. Treatment group (group V) was injected with anti IL-8 antibodies at dose of 1 000 μg for once and intervals for once 1 week.Results Experiments in vitro showed that the cell chemotaxis ability of anti IL-8 antibody in CaSki cells and pcDNA3.1-IL-8-SiHa cells was lower than that in the blank control group(CaSki cells:F=289.6,P =0.000; pcDNA3.1-IL-8-SiHa cells:F=79.0,P=0.005).GroupⅣwas taken as the example for its best anti-tumor effect in experiments in vivo. The tumor weight in groupⅣwas lower than that in groupⅠ[CaSki cells: (0.172±0.031) g vs. (0.735± 0.015) g, P＜ 0.05; pcDNA3.1-IL-8-SiHa cells: (0.400±0.029) g vs. (1.430±0.199) g, P＜ 0.05]. The tumor volume in groupⅣwas less than that in groupⅠ[CaSki cells:(0.049±0.028)cm3vs.(0.214±0.016) cm3,P＜0.05;pcDNA3.1-IL-8-SiHa cells:(0.063±0.022)cm3vs.(0.600±0.072)cm3,P＜0.05].The tumor growth curve also showed that tumor growth was slow, and the time of tumor formation as well as survival time was prolonged in anti IL-8 antibody treated group. The expression of mRNA in IL-8 in group IV was lower than that in group Ⅰ (CaSki cells: 0.58±0.06 vs. 1.15±0.13, P＜ 0.05; pcDNA3.1-IL-8-SiHa cells: 0.69±0.08 vs. 1.16±0.13,P＜0.05).The protein expression of IL-8 in groupⅣwas lower than that in groupⅠ(CaSki cells:126±29 vs.411±112,P＜0.05;pcDNA3.1-IL-8-SiHa cells:134±47 vs.327±69,P＜0.05).Apoptotic index in groupⅣwas higher than that in groupⅠ(CaSki cells:81.8±3.0 vs.26.0±5.6,P＜0.05;pcDNA3.1-IL-8-SiHa cells: 84.4±3.6 vs. 32.0±4.9, P＜0.05). Conclusion Anti IL-8 antibody can inhibit cell migration of human cervical cancer in vitro, inhibit growth and metastasis of transplantation tumor in vivo, and promote apoptosis and necrosis with a dose-dependent way in vivo.

Objective To study the distribution of connexin 43 (Cx43) in cervical cancer HeLa cells, and to verify the localization of Cx43 in mitochondria. Methods HeLa cells were segregated into cytoplasm, cell nucleus, mitochondria and supernatant after segregation by using the method of homogenate and centrifuge. Immunoelectron microscope was used to observe the morphology of mitochondria and the localization as well as the distribution of Cx43 in HeLa cells. Voltage-dependent anion channel 1 (VDAC1) was used to confirm the localization of mitochondria. Immunofluorescence was used to costain HeLa cells with Cx43 and mitochondrial marker VDAC1 to verify mitochondria localization of Cx43 in cervical cancer HeLa cells. Then Western blot was used to quantify the expression of Cx43 in fractions (cytoplasmic fraction,nuclear, mitochondria and post mitochondrial supernatant). Mitochondrial markers including VDAC1 and cytochrome c oxidaseⅣ(COXⅣ) were used to confirm mitochondria. Plasma membrane marker (LHR) was used to confirm plasma membrane. Results Immunoelectron microscope confirmed that the normal mitochondria or cystic swollen one could be seen in the complete HeLa cells and the detached HeLa cells mitochondria, with the presence of Cx43 and VDAC1 in detached mitochondria. Immunofluorescence showed Cx43 colocalized with VDAC1. There was a significant difference in the Cx43 expressions of the subcellular structure in the HeLa cells [cytoplasm (1.23±0.11), cell nucleus (0.39±0.09), mitochondria (3.67±0.59), supernatant after segregation (0.16±0.06); F =84.17, P ＜0.05]. It also showed that the relative amount of Cx43 in mitochondria was enriched. Conclusions Cx43 is enriched in mitochondria in cervical cancer HeLa cells. Therefore, Cx43 in mitochondria might be a potential target in diagnosis, therapy and prognosis of cervical cancer.

Objective To compare the different doses of low-temperature plasma (LTP) on wound healing in BALB/c mice so as to discuss the effects of the optimal dose of low-temperature plasma dealing with wound in mice and the acting mechanism of wound healing.Methods Adoptatmospheric pressure plasma jet discharged by the dielectric barrier was used to treat mouse skin wound.According to the processing time, the wounds were divided into 10s, 20s, 30s, 40s and 50s experimental groups, while naturally healing wounds served as negative controls and the wounds dealt with recombinant human epidermal growth factor served as positive controls.We recorded the wound size every day, observed the histopathological changes, the expression level of type Ⅰ collagen by immunofluorescence, and analyzed the composition of low-temperature plasma jet.Results The wounds with plasma treatment time of 10s, 20s, 30s, and 40s showed significant daily improvement and almost complete closure at days 12, 10, 7, 13, respectively.However, the wounds with plasma treatment time of 50s remained unhealed atday 14.The wounds in positive control group all healed, and the wound healing effect in positive control group could be achieved in 30s group.HE staining and immunofluorescence staining assays showed the optimal result of epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition in histological aspect at day 7 in 30 s group.The low-temperature plasma jet contained highly reactive free radicals of nitrogen and oxygen, which play an important role in wound healing process.Conclusion Appropriate doses of cold plasma can accelerate wound healing whereas over-doses of plasma can suppress wound healing.The process of wound healing may be related to reactive oxygen and nitrogen species in LTP.

Objective To introduce the concept of health promotion to brucellosis comprehensive prevention and control and then the effect was evaluated.We expect this article could provide scientific basis for prevention and control of brucellosis.Methods The study began in March 2014,a high-incidence district of brucellosis in Dali County was selected.Our study populations were divided to primary target groups and secondary target groups by the extent of exposure to sheep.We implemented general health campaigns,targeted health education,intervention and inducement,promotion of establish leading groups,and released relevant policies and rules for target population.According to the information from the questionnaire survey designed by us,before and after the intervention,the difference between the awareness rate of knowledge on brucellosis control,the health behavior formation rate and the effects of different intervention measures in primary target groups,were compared.The correct diagnostic rate in time (in 3 months),the eligible rate of trained health works,the change of the incidence of brucellosis in human cases,the perfection of the relevant policies on brucellosis control were analyzed,and the effectiveness of comprehensive prevention and control and health promotion strategies were evaluated.Results The disease awareness rate of target audience was 62.49％ (12 695/20 315) after the intervention which was 20.23％ (3 746/18 517) before the intervention.The awareness rate of primary target groups and secondary target groups was increased by 39.69％ [before intervention:33.75％ (1 624/4 812),after intervention:73.44％ (3 569/4 860)] and 43.57％ [before intervention:15.48％ (2 122/13 705),after intervention:59.05％ (9 126/15 455)],respectively.South of Luohe and north of Luohe increased by 37.70％ [before intervention:36.81％ (731/1 986),after intervention:74.51％ (1 453/1 950)] and 35.86％ [before intervention:35.06％ (711/2 028),after intervention:70.92％ (1 366/1 926)] after the intervention.The success rate of prevention and control skill on brucellosis in medical staff was 88.52％ (594/671);the correct diagnostic rate of new cases was 93.73％ (370/383).The proportion of new cases in the selected county in 2014 was 18.26％ (269/1 473) of the whole Shaanxi Province,the ratio decreased compared to that of the previous year.The proportion of new cases in 2015 was 6.14％ (75/1 221).The proportion of new cases in 2016 was 3.48％ (33/948).Conclusions Through the implementation of health promotion,health education and health promotion comprehensive measures,the disease awareness rate in target population has increased substantially.These measures are also able to lead focused population to develop health behavior and to decrease the incidence of brucellosis among people,and to realize the sustainable control of human brucellosis.

Objective To discuss on nursing of patients multiple- patient burn- blast combined injury, the cooperation of processes and quality control. Methods For 35 cases of burn- blast combined injury, emergency plan was initiated immediately, including staffing allocation, supplies allocation, nursing quality control and monitoring the inpatient areas, etc. Results 35 cases of burn- blast combined injury acquired immediate treatment of burn shock and nursing. Rescue rate of multiple- patient burn blast arrived 77.14%(27/35), with no case of nursing complication. Conclusions Timely allocation of nursing staff, rational quantity and structure, forceful organization and coordination, complete and timely supplies, correct quality control of emergence nursing and beneficial solutions are keys to ensure successive nursing of intensive patients of burn-blast combined injury, and also reflection of nursing quality guarantee.