Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Objective:To investigate the value of using ultrasound excited contrast agents to assess extracorporeal hydrostatic pressure on the basis of ultrasound contrast imaging.Methods:An extracorporeal hydrostatic pressure evaluation system was established. The changes in contrast intensity was first evaluated for the same concentration of microbubble contrast agent at ambient pressures of 20, 25, 30, 35, 40, and 45 cmH 2O. Contrast agents with the same initial intensity were placed at different pressures for 1 s, 3 s, and 5 s, and the percentage change in contrast agent intensity was analyzed to select the optimal excitation time. Finally, the contrast agent at different pressures was stimulated using an acoustic excitation device, and correlation analysis was performed using the Pearson product moment correlation coefficient. Linear regression analysis was used to establish the relationship between different pressures and the percentage change in intensity. Results:When the ambient pressure was varied under 6 gradients of 20, 25, 30, 35, 40, and 45 cmH 2O, the contrast strength decreased with the pressure increased, and there was a negative correlation between contrast strength and the pressure ( r=-0.971, P<0.001). Under different pressures, the contrast agent intensity showed different degrees of natural decrease in 1 s, 3 s, and 5 s. The difference in the percentage change in contrast agent intensity in each pressure gradient was not statistically significant in 1 s ( P>0.05), whereas the differences in the percentage change in contrast agent intensity in 3 s and 5 s were statistically significant in each pressure gradient (all P<0.05). After microbubble contrast agent was stimulated by ultrasound excitation for 1s, the percentage change in contrast agent intensity was significantly correlated with ambient pressure ( r=-0.976, P<0.001). A linear regression model was fitted with the percentage change in contrast agent intensity after 1 s of stimulation as the independent variable and the pressure as the dependent variable, with the model equation: y=60.075-2.559×x1, where x1 is the percentage change in contrast agent ( R2=0.952, P<0.001). Conclusions:The percentage change in contrast intensity after 1 s of ultrasound excitation of microbubble contrast agent is a favorable predictor of hydrostatic pressure at 6 pressure gradients of 20, 25, 30, 35, 40, and 45 cmH 2O, which may provide a new method for noninvasive monitoring of portal vein pressure for clinicans.

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

Objective:To investigate the effect of cesarean scar defect and endometrial cavity fluid on the pregnancy outcomes of infertility patients with previous cesarean scar uterus undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods:This was a retrospective cohort study. Totally 732 cases of patients with previous cesarean scar uterus were selected from frozen-thawed embryo transfer (FET) cycles in the Fertility Center, Shenzhen Zhongshan Urology Hospital from January 2019 to March 2020. They were divided into four groups: group A ( n=39) including patients with previous cesarean scar defect and without endometrial cavity fluid; group B ( n=82) including patients with previous cesarean scar defect and with endometrial cavity fluid; group C ( n=495) including patients without previous cesarean scar defect and without endometrial cavity fluid; group D ( n=116) including patients without previous cesarean scar defect and with endometrial cavity fluid. The general data and pregnancy outcomes were compared among these groups. Multivariate logistics regression analysis of pregnancy outcome indexes was performed. Results:The transplantation age of group A was higher than that of group B [(38.33±3.55) years vs. (36.93±3.59) years, P=0.045], the endometrial thickness of luteal transformation day and the rate of good-quality embryo transplantation of group C were higher than those of group D [(9.40±1.56) mm vs. (9.03±1.59) mm, P=0.025; 75.76% (375/495) vs. 65.52% (76/116), P=0.024]. The egg retrieval age of group A was higher than that of group C [(37.72±3.55) years vs. (36.25±4.52) years, P=0.049], but the endometrial thickness of luteal transformation day was thinner [(8.74±1.58) mm vs. (9.40±1.56) mm, P=0.012], and the differences were statistically significant. The implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group C were higher than those of group D [34.23% (230/672) vs. 22.58% (35/155), P=0.007; 48.28% (239/495) vs. 37.93% (44/116), P=0.044; 42.83% (212/495) vs. 30.17% (35/116), P=0.012]. The early abortion rate in group D was higher than that in group B [40.00% (14/35) vs. 17.24 % (5/29), P=0.047], the difference was statistically significant. Multivariate logistics regression analyses were used with adjustment for possible confounders: the maternal age at embryo transfer, the maternal age at egg retrieval, anti-Müllerian hormone (AMH),antral follicle count (AFC), basic follicle-stimulating hormone (FSH), endometrial CD138 results, FET protocol, and embryo attributes, the number of embryos transferred, embryo quality, the endometrial thickness and the progesterone value on the day of luteal transformation, the result showed that the implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group D were lower than those of group C [22.58% (35/155) vs. 34.23% (230/672), P=0.006; 37.93% (44/116) vs. 48.28% (239/495), P=0.047; 30.17% (35/116) vs. 42.83% (212/495), P=0.022] and the differences were statistically significant. The implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group B were higher than those of group D [29.52% (31/105) vs. 22.58% (35/155), P=0.049; 48.78% (40/82) vs. 37.93% (44/116), P=0.012; 35.37% (29/82) vs. 30.17% (35/116), P=0.030] and the differences were statistically significant. Conclusion:Endometrial cavity fluid is the main factor that obviously affects the pregnancy outcome of infertility patients with previous cesarean scar uterus undergoing FET cycles.

Objective:To investigate the effect of cesarean scar defect and endometrial cavity fluid on the pregnancy outcomes of infertility patients with previous cesarean scar uterus undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods:This was a retrospective cohort study. Totally 732 cases of patients with previous cesarean scar uterus were selected from frozen-thawed embryo transfer (FET) cycles in the Fertility Center, Shenzhen Zhongshan Urology Hospital from January 2019 to March 2020. They were divided into four groups: group A ( n=39) including patients with previous cesarean scar defect and without endometrial cavity fluid; group B ( n=82) including patients with previous cesarean scar defect and with endometrial cavity fluid; group C ( n=495) including patients without previous cesarean scar defect and without endometrial cavity fluid; group D ( n=116) including patients without previous cesarean scar defect and with endometrial cavity fluid. The general data and pregnancy outcomes were compared among these groups. Multivariate logistics regression analysis of pregnancy outcome indexes was performed. Results:The transplantation age of group A was higher than that of group B [(38.33±3.55) years vs. (36.93±3.59) years, P=0.045], the endometrial thickness of luteal transformation day and the rate of good-quality embryo transplantation of group C were higher than those of group D [(9.40±1.56) mm vs. (9.03±1.59) mm, P=0.025; 75.76% (375/495) vs. 65.52% (76/116), P=0.024]. The egg retrieval age of group A was higher than that of group C [(37.72±3.55) years vs. (36.25±4.52) years, P=0.049], but the endometrial thickness of luteal transformation day was thinner [(8.74±1.58) mm vs. (9.40±1.56) mm, P=0.012], and the differences were statistically significant. The implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group C were higher than those of group D [34.23% (230/672) vs. 22.58% (35/155), P=0.007; 48.28% (239/495) vs. 37.93% (44/116), P=0.044; 42.83% (212/495) vs. 30.17% (35/116), P=0.012]. The early abortion rate in group D was higher than that in group B [40.00% (14/35) vs. 17.24 % (5/29), P=0.047], the difference was statistically significant. Multivariate logistics regression analyses were used with adjustment for possible confounders: the maternal age at embryo transfer, the maternal age at egg retrieval, anti-Müllerian hormone (AMH),antral follicle count (AFC), basic follicle-stimulating hormone (FSH), endometrial CD138 results, FET protocol, and embryo attributes, the number of embryos transferred, embryo quality, the endometrial thickness and the progesterone value on the day of luteal transformation, the result showed that the implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group D were lower than those of group C [22.58% (35/155) vs. 34.23% (230/672), P=0.006; 37.93% (44/116) vs. 48.28% (239/495), P=0.047; 30.17% (35/116) vs. 42.83% (212/495), P=0.022] and the differences were statistically significant. The implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group B were higher than those of group D [29.52% (31/105) vs. 22.58% (35/155), P=0.049; 48.78% (40/82) vs. 37.93% (44/116), P=0.012; 35.37% (29/82) vs. 30.17% (35/116), P=0.030] and the differences were statistically significant. Conclusion:Endometrial cavity fluid is the main factor that obviously affects the pregnancy outcome of infertility patients with previous cesarean scar uterus undergoing FET cycles.

Objective:To investigate the effects of quaternary ammonium salt of chitosan combined with closed irrigation on ischemia-reperfusion injury (I/R) in rat skin flap.Methods:Fourty-five adult male SD rats were randomly divided into 3 groups: sham-operated group, I/R group and chitosan group. Before operation, collection of arterial blood for testing PCT and hs-CRP were used as basic values. Right low abdominal island flap fed by the superficial epigastric artery was created in rats of all three groups. After operation, we flushed and dressed the wound with 10% saline of sham-operated group and I/R group. Quaternary ammonium salt of chitosan combined with closed irrigation were used in chitosan group. Flaps were assessed histologically at 3 d, 5 d and 7 d of reperfusion. The tissue was collected to make the SOD, MDA and PCT, hs-CRP testing, pathological section observation and to calculate the flap survival rate.Results:Marked neutrophil infiltration and edema were observed in I/R group, while less neutrophil infiltration was observed in chitosan group. Compared with the sham-operated group, the PCT and hs-CRP levels of the I/R group after modeling for 3 and 5 days were significantly increased. There were statistically significant differences ( P<0.05); Compared with the sham-operated group, the PCT and hs-CRP levels of the Chitosan group after modeling for 3 days, 5 days were significantly increased. There were statistically significant differences ( P<0.05); Compared with the I/R group, the PCT and hs-CRP levels of the Chitosan group after modeling for 3 and 5 days were significantly induced. There were statistically significant differences ( P<0.05); after modeling for 7 days, the values between all groups were no statistically significant differences ( P>0.01). Compared with the sham-operated group, the SOD level of the I/R group after modeling for 3, 5 and 7 days was significantly induced. MDA level was significantly increaesd; compared with the sham-operated group, the SOD level of the Chitosan group after modeling for 3, 5 and 7 days were significantly induced. MDA level was significantly increaesd; Compared with the I/R group, the SOD level of the chitosan group after modeling for 3, 5 and 7 days were significantly increased. MDA level was significantly induced. They all had statistically significant differences ( P<0.05). In the chitosan group, the survival of flaps was (85.34±10.02)%, which was significantly greater than the I/R group, in which only (41.11±14.17)% of the flap survived ( P<0.05). Conclusions:Quaternary ammonium salt of chitosan combined with closed irrigation can significantly improve flap survival, reduce I/R in transplanted rats＇ skin flaps.

Objective To understand the cognitive level of chronic obstructive pulmonary disease (COPD) disease management and pulmonary rehabilitation among medical staff in the respiratory departments and community of public health institutions in Panyu of Guangzhou, in order to assess the status of prevention and treatment of COPD in this area. Methods From March to October 2017, a questionnaire survey was conducted among 339 medical staff in Panyu, including respiratory doctors, nurses and therapists of four tertiary hospitals, five secondary hospitals, and three first-level hospitals, GPs, nurses and therapists at 16 community health service centres, among them, there are 147 respiratory and general practitioners (hereinafter referred to as doctors), 171 respiratory and general nurses (hereinafter collectively referred to as nurses), and 22 rehabilitation therapists (hereinafter collectively referred to as therapists). Using Epidata software to create questionnaire database entry data. Results The awareness rate of COPD airflow limitation severity of nurses was only 19.9％, which was lower than that of doctors (39.7％) and therapists (22.7％). Doctors, nurses, and therapists are familiar with the low percentage of the GOLD guidelines, which are respectively only 12.3％, 7.6％, and 4.5％. Nurses were diagnosed with pulmonary function as a basis for COPD, and the awareness rate was only 60.2％ lower than that of doctors (82.9％) and therapists (81.8％). In alleviating COPD patients′shortness of breath, only 31.8％therapists chose short-acting beta-agonists, lower than doctors (61％) and nurses (45％). There is disagreement about the long-term use of inhaled corticosteroids in COPD. Medical staff have the highest awareness of lip-reducing and abdominal breathing, followed by Taiji and Ba Duan Jin exercises, and low awareness of modern rehabilitation programs such as elastic bands, upper and lower limb exercises. The effective pulmonary rehabilitation program should last at least 8 weeks, and the awareness rate of this therapy practice was 40.9％, higher than doctors (13.7％) and nurses (18.1％). Medical staff believe that the main factors affecting patient compliance are the cost of the drug and the patient′s lack of understanding of the benefits of the treatment. Additionally, 40.4％ of doctors, 51.5％ of nurses, and 54.5％of therapists believe that community health services cannot manage COPD. The reasons that affect community management of COPD, doctors believe that patient compliance and lack of man power, nurses believe that the main shortage of manpower and equipment, the therapist believes that the lack of medical awareness and poor patient compliance. Conclusion Doctors, nurses, and therapists have inconsistent understandings of COPD disease management and pulmonary rehabilitation, and each has its own focus. It is necessary to strengthen learning exchanges for each weak knowledge point. The awareness rate of modern rehabilitation exercise for pulmonary rehabilitation is not as high as that of traditional Chinese medicine. It is necessary to pay attention to the promotion of the benefits and significance of COPD pulmonary rehabilitation treatment and improve compliance.

Objective: To evaluate the consistency between prostate biopsy and postoperative pathological grade, analyze the influencing factors that may lead to upgrade or downgrade, and to establish a prediction model. Methods: The clinical data of biopsy GS3+ 3=6(GR1, 330 cases) and GS3+ 4=7(GR2, 340 cases) patients from January 2013 to December 2018 in the first affiliated hospital, College of Medicine of Zhejiang university were retrospectively analyzed. The median age was 67 years old(ranging 35 to 100 years old). The median BMI was 23.74 kg/m²(ranging 16.22-38.74 kg/m²). The Median tPSA was 10.266 ng/ml(ranging 0.017-147.575 ng/ml). The median prostate volume was 29.43 ml(5.92-187.20 ml). The median PSAD was 0.34 (ranging 0.01-4.02). The median percentage of positive puncture cores was 0.25 (ranging 0.08-1.00). There were 161 patients in clinical stage ≤T_1c, 344 patients in T_2a-T_2c and 165 patients in clinical stage ≥T₃. 670 cases all accepted the radical prostatectomy. Consistency of prostate biopsy and radical prostatectomy Gleason grade was recorded. If the postoperative Gleason grade was higher than that in biopsy, it was defined as upgrade. Otherwise, it was defined as downgrade. Multivariate logistic regression model was used to evaluate the influencing factors leading to upgrades in GR1 patients or downgrades in GR2 patients. Nomograms were drawn based on the models with AUC and Horsmer-Lemeshaw test conducted to test the discrimination and calibration of the models. Results: Among the 670 patients included, 165 cases (50.0% of GR1) upgrades and 27 cases (7.9% of GR2) downgrades. PSAD≥0.25(OR=3.015) and clinical stage≥T_2b(OR=7.185)were independent influencing factors for the upgrade in GR1 patients, while PSAD<0.15(OR=4.208) and clinical stage≤T_1c(OR=4.530) were independent influencing factors for downgrade. The nomograms were drawn with the above variables. The AUC of the model (0.781 for GR1 group, 0.741 for GR2 group) and the hosmer-remeshaw test results (P=0.993 for GR1 group, P=0.234 for GR2 group) show that the nomograms have good discrimination and calibration. Conclusions PSAD and clinical stage are independent influencing factors for the upgrade or downgrade. Nomograms may provide help for clinicians to judge the accuracy of prostate biopsy. However, the nomograms still needs to be verified in clinical practice

Objective To evaluate the clinical and pathological features of patients with prostate cancer who were diagnosed by single positive core biopsy and treated by radical prostatectomy (RP).Methods Between July 2012 and June 2016,164 patients with prostate cancer diagnosed by single positive core biopsy underwent RP.The mean age was 66.3 years old (ranged 41-82 years old),and the mean PSA level was 12.3 ng/ml (ranged 0.6-59.5 ng/ml).The biopsy Gleason score showed 6 scores in 113 cases,3 + 4 =7 scores in 21 cases,4 + 3 =7 scores in 18 cases,≥8 scores in 12 cases.Clinical stage was cT1 in 71 cases,cT2 in 92 cases,and cT3 in 1 case.The patients were divided into subgroups according to age,preoperative PSA level,biopsy Gleason score and clinical stage,and the pathological results were compared among these subgroups.Results Of the 164 patients,67 cases had Gleason score ≤ 6,52 cases Gleason score 3 + 4 =7,24 case Gleason score 4 + 3 =7,and 11 cases Gleason score ≥ 8.Ten patients had pT0 disease according to the RP specimen,3 had extraprostatic extensions,5 had seminal vesicle invasions,and 24 had positive surgical margins.Compared to the biopsy,the Gleason score of RP specimens was higher in 53 cases,concordant in 77 cases,and lower in 24 cases.There was no significant difference in the postoperative pathological features between the age group ＜ 70 years and the group ≥ 70 years.Compared with PSA ＜ 10 ng/ml,the likelihood of postoperative Gleason score ＞ 7 was significantly increased in PSA ≥10 ng/ml group [41.4％ (36/87) vs.66.2％ (51/77),P＜0.05].When the biopsy Gleason score was divided into four groups (6,3 + 4 =7,4 + 3 =7,≥ 8),there were significant differences in postoperative pathological stages among the four groups (P ＜ 0.05),and the patients with biopsy Gleason score 6 were more likely to have no residual cancer (stage T0) when compared with other Gleason scores [8.8％ (10/113) vs.0,P =0.09].The probability of no residual cancer in clinical T1 stage patients was significantly higher than that in T2 stage [11.3％ (8/71) vs.2.8％ (2/92),P =0.02],while the probability of Gleason score upgrading was significantly lower [23.9％ (17/71) vs.39.1％ (36/92),P ＜ 0.05].Conclusions Most single core prostate cancer have clinically significant disease.The treatment plan must be evaluated individually for patients with single core prostate cancer.