Objective To design and synthesize the conjugate (compound 1) of chlorin e₆ (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH₃OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P₂S₅ in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N₂H₄·H₂O) in CH₃OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 17¹- and 15² cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC₅₀ value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, ¹H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development.

Objective:To construct an evaluation the index system of entrustable professional activities for resident training doctors in psychiatric department,and to provide reference for formulating training strategies and assessment standards.Entrustable professional activities refers to the ability of trainees to perform and complete spe-cific clinical tasks independently after they have been trusted.Methods:Through documental analysis and semi-structured interviews,the item database of entrustable professional activities for psychiatric resident training physi-cians was established.Delphi consultation was conducted among 63 experts in the field of psychiatry from 7 national resident training bases and 3 medical colleges in China.Indicators were comprehensively screened and sorted out,and indicators at all levels and their weights were determined by the analytic hierarchy process.Results:A hierarchi-cal evaluation index system of entrustable professional activities for psychiatric resident training doctors was con-structed,including 4 first-level indicators,17 second-level indicators and 68 third-level indicators.The weights of the first-level,second-level and third-level indicators were determined.Conclusion:The evaluation index system of en-trustable professional activities is comprehensive and systematic,which is suitable for clinical work and convenient for practical application.It could provide quantitative standards for the assessment of psychiatric residents and pro-mote the improvement of training quality.

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Objective: To investigate the social support of medical students during the outbreak of COVID-19 and its mediating effect on the correlation between epidemic exposure and depression with anxiety. Methods: A total of 5 593 medical students were enrolled, and Social Support Rating Scale(SSRS), Patient Health Questionnaire-9 and 7-tiem Generalize Anxiety Disorder Scale were used to measure. Results: The social support score of SSRS of male students was lower than that of female students (t=-4.36, P<0.05) and juniors and seniors scored lower than other grades(F=4.84, P<0.05). Epidemic exposure proportion was positively correlated with both depressive proportionand anxiety proportion(r=0.05, 0.06, P<0.01), while epidemic exposure and depressive proportion and anxiety proportion were negatively correlated with social support score(r=-0.05, -0.25, -0.19, P<0.01). After controlling for gender and grade, the mediating effect of social support in the correlation between epidemic exposure and depression accounted for 26.6% of the total effect, and the mediating effect of subjective support and supportive utilization was 32.3% and 25.7% respectively. After controlling for gender and grade, the mediating effect of social support in the correlation between epidemic exposure and depression accounted for 20.0% of the total effect, and the mediating effect of subjective support and supportive utilization was 15.9% and 12.2% respectively. Conclusion Social support has partially mediating effect in the correlation between epidemic exposure with depression and anxiety.

Objective To designe, synthesize a series of chlorin p₆ ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p₆ trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH₂N₂. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by ¹H-NMR, ¹³C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p₆ ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.

ObjectiveTo investigate the value of peripheral blood long non-coding RNA-LET (lncRNA-LET) in the diagnosis of chronic hepatitis B (CHB) cirrhosis, and to provide a basis for early clinical diagnosis and treatment of liver cirrhosis. MethodsA total of 175 CHB patients who attended The Affiliated Hospital of Chengde Medical University from March 2017 to May 2019 were enrolled, among whom 52 patients with hepatitis B cirrhosis were enrolled as cirrhosis group and 123 patients without the pathological changes of liver cirrhosis were enrolled as non-cirrhosis group. A total of 40 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as normal control group. Liver function parameters and the level of lncRNA-LET in peripheral blood were measured for all subjects. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of ranked data. A Pearson correlation analysis was performed to investigate correlation. The receiver operating characteristic (ROC) curve was used to investigate the value of peripheral blood lncRNA-LET in predicting liver cirrhosis. Results Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly higher serum levels of the liver function parameters total bilirubin (TBil), total bile acid (TBA), albumin (Alb), and alanine aminotransferase (ALT) (all P＜0.05) and a significantly lower serum level of cholinesterase (ChE) (P＜0.05); compared with the non-cirrhosis group, the cirrhosis group had significantly higher serum levels of TBil, TBA, Alb, and ALT (all P＜0.05) and a significantly lower serum level of ChE (P＜0.05). Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood (P＜0.05), and the cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood than the non-cirrhosis group (P＜0.05). The relative expression of lncRNA-LET decreased significantly with the increase in liver fibrosis stage (P＜0.05). In the patients with CHB, the relative expression of lncRNA-LET in peripheral blood was negatively correlated with liver fibrosis stage, TBil, TBA, Alb, and ALT (r=-0.352,-0.372,-0.364, and -0.410, all P＜0.001) and was positively correlated with ChE (r=0.340, P＜0.001). The ROC curve was used to analyze the value of peripheral blood lncRNA-LET in predicting liver cirrhosis, and the area under the ROC curve was 0934, with an optimal cut-off value of 0.833, a sensitivity of 84.57%, and a specificity of 80.57%. ConclusionThe expression level of lncRNA-LET in peripheral blood decreases with the progression of liver fibrosis and has a good value in the diagnosis of CHB cirrhosis, and therefore, it can be used as a potential biological indicator for the diagnosis of liver cirrhosis.

Objective:To evaluate the feasibility of placement of S 2 alar iliac screw (S 2AI) using free-hand technique for sacrapelvic fusion in lumbar degenerative scoliosis. Methods:Eighteen patients with Lumbar Degenerative Scoliosis treated by S 2AI screw fixation at Department of Orthopedics, General Hospital of Southern Theater Command of People′s Liberation Army and Department of Orthopedics, 89th hospital of People′s Liberation Army from August 2014 to October 2018 were analyzed retrospectively. There were 5 males and 13 females, aged 63.2 years old (range:55 to 71 years old).Parameters of spine including: Cobb Angle, C 7 plumb line -center sacral vertical line (C 7PL-CSVL), lumbar lordosis(LL), sagittal vertical axis(SVA), pelvic incidence(PI), pelvic tilt(PT), sacral slope (SS) and pI-LL were measured on the whole spine X-ray before operation and at final follow-up. Pelvic CT scan was performed postoperatively to assess the accuracy of S 2AI placement. Oswestry disability Index (ODI) was also recorded. The data were compared by paired t test or Wilcoxon tests. Results:All patients were followed up for 23.7 months (range: 12~62 months).At the last follow up, Cobb Angle decreased from (32.28±4.97) °preoperative to (6.56±3.20) ° ( t=41.142, P<0.01) and C 7PL-CSVL deceased from (1.11±2.07) cm preoperative to (0.18±1.08) cm ( t=41.142, P=0.06) .LL improved from (-22.39±13.07) °preoperative to (-36.39±4.29) ° ( t=4.470, P<0.01) , PI-LL decreased from (26.83±14.83)°preoperative to (13.72±8.3)° ( t=4.396, P<0.01) , PT decreased from (27.94±4.26) °to (23.39±6.08) ° ( t=2.680, P=0.02) , and SS increased from (22.22±6.36) °to (26.28±7.24) ° ( t=-2.178, P=0.04) .SVA decreased from (6.54±4.51) cm preoperative to (2.62±1.29) cm ( t=3.052, P=0.01) .ODI decreased from 0.58(0.40) ( M( QR)) to 0.18 (0.15) ( Z=-4.567, P<0.01) .No complications such as nerve and blood vessel injury occurred during the operation. A total of 32 S 2AI screws were placed, 3 screws were placed with mild to moderate cortical breaches, 2 were perforated the pelvis ventrally, 1 was perforated posteriorly, with no clinically notable neurovascular or visceral complications. Eight patients finished the SRS-22 questionnaire, with mean score of 4.4 in terms of satisfaction with management. Conclusions:Free-hand technique of S 2AI screw placement for sacrapelvic fusion in degenerative lumbar scoliosis is safe and feasible.S 2AI fixation in DLS can provide great correction of deformity, maintain the stability of lumbo-pelvic area and improve the clinical symptoms.

Objective:To evaluate the feasibility of placement of S 2 alar iliac screw (S 2AI) using free-hand technique for sacrapelvic fusion in lumbar degenerative scoliosis. Methods:Eighteen patients with Lumbar Degenerative Scoliosis treated by S 2AI screw fixation at Department of Orthopedics, General Hospital of Southern Theater Command of People′s Liberation Army and Department of Orthopedics, 89th hospital of People′s Liberation Army from August 2014 to October 2018 were analyzed retrospectively. There were 5 males and 13 females, aged 63.2 years old (range:55 to 71 years old).Parameters of spine including: Cobb Angle, C 7 plumb line -center sacral vertical line (C 7PL-CSVL), lumbar lordosis(LL), sagittal vertical axis(SVA), pelvic incidence(PI), pelvic tilt(PT), sacral slope (SS) and pI-LL were measured on the whole spine X-ray before operation and at final follow-up. Pelvic CT scan was performed postoperatively to assess the accuracy of S 2AI placement. Oswestry disability Index (ODI) was also recorded. The data were compared by paired t test or Wilcoxon tests. Results:All patients were followed up for 23.7 months (range: 12~62 months).At the last follow up, Cobb Angle decreased from (32.28±4.97) °preoperative to (6.56±3.20) ° ( t=41.142, P<0.01) and C 7PL-CSVL deceased from (1.11±2.07) cm preoperative to (0.18±1.08) cm ( t=41.142, P=0.06) .LL improved from (-22.39±13.07) °preoperative to (-36.39±4.29) ° ( t=4.470, P<0.01) , PI-LL decreased from (26.83±14.83)°preoperative to (13.72±8.3)° ( t=4.396, P<0.01) , PT decreased from (27.94±4.26) °to (23.39±6.08) ° ( t=2.680, P=0.02) , and SS increased from (22.22±6.36) °to (26.28±7.24) ° ( t=-2.178, P=0.04) .SVA decreased from (6.54±4.51) cm preoperative to (2.62±1.29) cm ( t=3.052, P=0.01) .ODI decreased from 0.58(0.40) ( M( QR)) to 0.18 (0.15) ( Z=-4.567, P<0.01) .No complications such as nerve and blood vessel injury occurred during the operation. A total of 32 S 2AI screws were placed, 3 screws were placed with mild to moderate cortical breaches, 2 were perforated the pelvis ventrally, 1 was perforated posteriorly, with no clinically notable neurovascular or visceral complications. Eight patients finished the SRS-22 questionnaire, with mean score of 4.4 in terms of satisfaction with management. Conclusions:Free-hand technique of S 2AI screw placement for sacrapelvic fusion in degenerative lumbar scoliosis is safe and feasible.S 2AI fixation in DLS can provide great correction of deformity, maintain the stability of lumbo-pelvic area and improve the clinical symptoms.

Objective To establish a quality standard of huangqi baoxin mixture and improve its quality control system. Methods The qualitative analysis of Astragalus membranaceus,Salvia miltiorrhiza,Forsythia,and Angelica were performed by TLC.The content determination of astragalosideⅣin the huangqi baoxin mixture was conducted by HPLC-ELSD. Results As-tragalus membranaceus,Salvia miltiorrhiza,Forsythia,and Angelica in the huangqi baoxin mixture could be accurately identified by TLC.The linear range of astragaloside Ⅳ was 1.224-10.20 μg (r=0.999 5).RSDs of precision,stability,and reproducibility tests were lower than 3.0%;the recovery was 96.2%-102.9% with RSD at 2.20% (n=6). Conclusion The established quan-titative method is simple,accurate,and reliable with high specificity which can be used to control the quality of huangqi baoxin mixture.

Objective To investigate the influencing factors of the cognitive deficits in schizophrenic patients with diabetes.Methods 578 inpatients with schizophrenia and 400 healthy adults were collected.578 schizophrenic patients were divided into schizophrenia group with type 2 diabetes (combined group,n=277) and schizophrenia without type 2 diabetes (single disease group,n=301).The cognitive function of all subjects were examined by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).The clinical symptoms of patients with schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS).Fasting glucose,lipids,hemoglobin A1c (HbA1c) and insulin levels were measured.Results The total score and factor scores of RBANS in the combined group were lower than those in the healthy control group (total score (70.51 ± 14.43) vs (80.04 ± 15.14),immediate memory (62.65 ± 16.81) vs (75.66± 17.33),visual span(83.60±20.81) vs (87.61 ± 15.61),verbal function(85.58± 14.64) vs (93.88± 13.10),attention function (73.66± 17.52) vs (87.42±20.37),delayed memory(75.27± 17.80) vs (86.27± 15.27),all P＜0.05).The total score of RBANS,immediate memory and attention function factor were lower in the combined group than that in the single disease group ((70.51±14.43) vs (75.02±15.25),(62.65±16.81) vs (67.37±19.12),(73.66±17.52) vs (84.17±15.22),all P＜0.05).Multiple linear stepwise regression analysis showed that education,negative symptoms,positive symptoms,BMI,HbAc 1,course of disease and antipsychotic type were the influencing factors of cognitive impairment in schizophrenic patients with diabetes.Conclusion The cognitive impairment of schizophrenic patients with diabetes is more serious and affected by many factors.Targeted early intervention can help reduce cognitive impairment.