ObjectiveTo evaluate the effect of sex on phenotypic stability in mouse models of chemotherapy-induced alopecia (CIA) induced by cyclophosphamide (CYP) or paclitaxel (PTX), and to explore potential mechanisms underlying phenotypic heterogeneity in female mice. MethodsTwenty-eight wild-type specific pathogen-free (SPF) C57BL/6J mice (half male and half female) aged 6-8 weeks were selected for synchronous back hair removal. On the 9th day after hair removal (T0), the mice were randomly divided into a wild-type female CYP group, a wild-type male CYP group, a female negative control group and a male negative control group. Mice in the CYP groups were intraperitoneally injected with a single dose of 120 mg/kg CYP, and mice in the negative control groups were intraperitoneally injected with the same volume of normal saline. Subsequently, the phenotypic changes of the CIA model induced by CYP were continuously observed and photographed. Eleven 6-week-old SPF female C57BL/6J mice underwent bilateral ovariectomy (OVX group). Following successful surgery, these mice and five XY (Sry⁻) mice bred from Four Core Genotypes breeding stock were used to establish the chemotherapy-induced alopecia (CIA) model using the same protocol. Serum was collected from mice in the OVX group, wild-type female CYP group, and wild-type male CYP group on T7 after CYP administration for steroid hormone analysis by mass spectrometry to evaluate the effects of gonadal estrogen and sex chromosome background changes on the stability of the CYP-induced female alopecic phenotype. Finally, twenty SPF C57BL/6J mice aged 6-8 weeks (half male and half female) were randomly divided into a PTX low-dose group and a PTX high-dose group. On the 9th day after simultaneous hair removal, PTX was injected intraperitoneally at a single dose of 80 mg/kg or 120 mg/kg, respectively. Mice from the PTX low-dose group and the PTX high-dose group were continuously observed and photographed to compare the intra-group consistency of the phenotypes of female and male mice. Six SPF C57BL/6J mice (half male and half female) aged 6-8 weeks were used to repeat the construction method of the PTX low-dose group, and the hair follicle histological examination was performed at T0, T4, T7, T14 and T21, respectively, to observe the damage caused by PTX to hair follicle regeneration. ResultsThe phenotypes of CYP-induced male CIA mice are stable and reproducible. There are obvious individual differences in the alopecia phenotype in the CYP-induced female CIA model mice, which may be mainly caused by the differences in the relevant estrogens in the estrous cycle. The difference between OVX+CYP group and XY (Sry⁻) +CYP group disappeared, suggesting that ovarian-derived hormones and XY (Sry⁻) sex chromosome background may be involved in the formation of phenotypic heterogeneity of CYP-induced alopecia in female mice. The mice in the high-dose PTX group and the low-dose PTX group showed a relatively consistent alopecia and regrowth process, and there was no significant sex difference. ConclusionCYP-induced CIA is strongly influenced by sex, and ovariectomy or alteration of the sex chromosome background can improve the consistency of CYP-induced alopecic phenotypes in female mice. PTX-induced CIA shows good phenotypic consistency in both female and male mice, indicating broad applicability across sexes. Taken together, the choice of animal sex in CIA model construction, mechanistic studies, and evaluation of anti-alopecia interventions should take into account the type of chemotherapeutic agent, the study objective, and the required degree of phenotypic stability. Sex should therefore be considered an important variable in model standardization and interpretation of experimental findings.

Objective:To study the life characteristics and related risk factors of patients with depression in Shandong Province.Methods:Based on the 2015 mental epidemiological survey database in Shandong Province,a total of 832 patients with depression,807 high-risk individuals with depression,and 819 low-risk individuals were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)and the Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders,Research Version(SCID-I/P).In 2020,SCID-I/P was used for re diagnosis,and the General Health Questionnaire(GHQ-12),Simple Quality of Life question-naire,Pittsburgh sleep quality index(PSQI),Childhood Trauma Questionnaire(CTQ),Social Support Rating Scale(SSRS),Global Pain Scale(GPS),Montreal Cognitive Assessment(MoCA),Simplified Coping Style Question-naire(SCSQ)were used for evaluation.Compare changes in the quality of life of depression patients and construct a risk factor model.Results:Patients with depression had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in the high-and low-risk groups,those in remission of depression had higher scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in non-re-mission,and those with new-onset disorder in the high-and low-risk groups had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those with no-onset disorder(Ps＜0.001).Depres-sion diagnosis and PSQI scale scores at baseline negatively predicted at retest after 5 years(β=-0.06,-0.15),while coping style tendencies at baseline positively predicted(β=0.06).The simple quality of life questionnaire at baseline negatively predicted depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,and PSQI scale scores at retest after 5 years(β=-0.11,-0.17,-0.09),while the simple quality of life question-naire at baseline positively predicted coping style tendencies at retest after 5 years(β=0.13).Depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,PSQI scale scores at retest after 5 years,coping style tendencies at retest after 5 years,SSRS scale scores,CTQ scale scores,GPS scale scores,and the simple quality of life questionnaire at baseline all influenced the simple quality of life questionnaire at retest after 5 years through ei-ther direct or indirect pathways.Conclusion:It suggest that the quality of life is lower in patients with depression than in the general population.Depression diagnosis,sleep,mental health,pain,social support,childhood trauma and coping are direct and indirect risk factors affecting life.

Radiotherapy is the most common treatment for nasopharyngeal carcinoma, and the radiotherapy technique is essential for the prognosis of nasopharyngeal carcinoma. Due to the complexity of the structure of the intensity-modulated device and the accuracy of the clinical requirements of radiotherapy, it is inevitable that higher requirements will be imposed on the process of intensity-modulated radiotherapy. Currently, gaps exist in the radiotherapy equipment and personnel qualification among radiotherapy units, and thus the homogenization in the radiotherapy remains to be strengthened in China. With the application of radiotherapy information management system, digital medicine and artificial intelligence technologies in the field of radiotherapy, the original process fails to meet the application needs of the new precise radiotherapy technology. Therefore, this process is designed based on the existing radiotherapy procedures for nasopharyngeal carcinoma in combination with the latest developments in the field of radiotherapy, aiming to establish a novel standard process recommendation, ensuring the standardization and homogenization of radiotherapy and achieve the individualized intensity-modulated radiotherapy for nasopharyngeal carcinoma patients.

Objective To evaluate the effects of sevoflurane preconditioning on wnt/glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling pathway during myocardial ischemia-reperfusion (I/R) injury in rats in vitro.Methods Ault male Wistar rats,weighing 220-280 g,were heparinized and anesthetized with intraperitoneal 3％ pentobarbital 30 mg/kg.Their hearts were rapidly excised and perfused in a langendorff apparatus with oxygenated (95％ O2-5％ CO2) K-H solution at 37 ℃.After 15 min of equilibration,36 isolated hearts were randomly divided into 3 groups (n=12 each) using a random number table:sham operation group (group S),group I/R and sevoflurane preconditioning group (group SP).After 30 min of equilibration,the hearts were continuously perfused for 150 min in group S.The isolated hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion.In SP group,the hearts were perfused for 15 min with K-H solution containing 2.4％ sevoflurane,followed by 5 min washout before reperfusion.At the end of equilibration and 30 min of reperfusion,HR,left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP) and ± dp/dtmax were recorded.The severity of arrhythmias was assessed during reperfusion.At 60 min of reperfusion,3 hearts in each group were chosen for measurement of expression of wnt3a,phosphor-GSK-3β (p-GSK-3β) and β-catenin (by Western blot).At 120 min of reperfusion,6 hearts in each group were chosen for determination of myocardial infarct size by TTC staining.Results Compared with group S,HR,LVDP,+dp/dtmax and -dp/dtmax were significantly decreased,and LVEDP was increased at 30 min of reperfusion,arrhythmia scores and the percentage of myocardial infarct size were increased,and the expression of wnt3a,p-GSK-3β and β-catenin was down-regulated in I/R group.Compared with group I/R,HR,LVDP,+dp/dtmax and-dp/dtmax were significantly increased,and LVEDP was decreased at 30 min of reperfusion,arrhythmia scores and the percentage of myocardial infarct size were decreased,and the expression of wnt3a,p-GSK-3β and β-catenin was up-regulated in group SP.Conclusion Sevoflurane preconditioning attenuates myocardial I/R injury by activating wnt/GSK-3β/β-catenin signaling pathway in isolated rat hearts.

Objective:To explore the value of matrix metalloproteinase (MMP)‐7 ,MMP‐10 and tissue inhibitor of matrix metalloproteinase(TIMP)‐1 ,TIMP‐2 in the differential diagnosis of benign and malignant pleural effusion .Methods :The concentrations of MMP‐7 ,MMP‐10 ,TIMP‐1 and TIMP‐2 in 38 cases of malignant pleural effusion and 50 cases of benign pleural effusion were detected by enzyme‐linked immunosorbent assay(ELISA) .Results:(1)The concentrations of MMP‐7 , MMP‐10 and the MMPs/TIMPs ratios were higher in malignant pleural effusion than those in benign pleural effusion (P<0 .01) .There was no significant difference in the concentrations of TIMP‐1 ,TIMP‐2 between benign pleural effusion and malignant pleural effusion(P> 0 .05) .(2)While single‐index were used in the differential diagnosis of benign and malignant pleural effusion ,MMP‐7 ,MMP10 and the MMPs/TIMPs ratios showed good diagnostic efficiency .The demarcation points of MMP‐7 ,MMP‐10 ,MMP‐7/TIMP‐1 ratio ,MMP‐10/TIMP‐1 ratio ,MMP‐7/TIMP‐2 ratio and MMP‐10/TIMP‐2 ratio were 328 .17 ng/mL ,246 .13 ng/mL ,0 .635 ,0 .478 ,0 .564 ,0 .438 , respectively . The corresponding sensitivities of them were 81 .6% ,97 .4% ,81 .6% ,89 .5% ,78 .9% ,74 .2% ,respectively .The corresponding specificities of them were 66 .0% ,60 .0% , 80 .0% ,70 .0% ,68 .0% , 72 .0% , respectively . Conclusions :M M P7 ,M M P‐10 are closely related to the development of malignant pleural effusion .The imbalance of MMPs/TIMPs ratio plays a great role in the pathogenesis of malignant pleural effusion .To detect MMP7 ,MMP‐10 and MMPs/TIMPs ratio of pleural effusion is conducive to the differential diagnosis of benign and malignant pleural effusion .

Objective To evaluate the effects of sevoflurane preconditioning on zonula occludens-1 (ZO-1) during myocardial ischemia-reperfusion (I/R) in rats in vitro.Methods Adult male Wistar rats,weighing 250-300 g,were anesthetized with intraperitoneal pentobarbital 30 mg/kg and heparinized.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃.Eighteen isolated rat hearts were randomly assigned into 3 groups (n =6 each) using a random number table:control group (group C),group I/R and sevoflurane preconditioning group (group S).At 10 min of equilibration,the hearts were perfused with K-H solution for 110 min in group C,the hearts were perfused with K-H solution for 20 min,and then subjected to 30 min of ischemia followed by 60 min of reperfusion in group I/R,and the hearts were perfused with K-H solution saturated with 3％ sevoflurane for 15 min followed by 5 min washout,and then subjected to 30 min of ischemia followed by 60 min of reperfusion in group S.At the end of equilibration,immediately before ischemia,and at 15 and 60 min of reperfusion (T1,2),HR,left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),+ dp/dtmax and-dp/dtmax were recorded.The development of arrhythmias was recorded during reperfusion and scored.At 60 min of reperfusion,myocardial specimens were obtained from the apex of heart for determination of the expression of ZO-1 in myocardial tissues (by Western blot) and for observation of distribution of ZO-1 and connexin43 (Cx43) (by immunofluorescence).Results Compared with group C,HR,LVDP,+ dp/dtmax and-dp/dtmax were significantly decreased and LVEDP was increased at 15 and 60 min of reperfusion,scores of arrhythmia was increased,and ZO-1 expression was down-regulated in I/R group.Compared with group I/R,HR,LVDP,+ dp/dtmax and-dp/dtmax were significantly increased and LVEDP was decreased at 15 and 60 min of reperfusion,arrhythmia was decreased,and ZO-1 expression was up-regulated in group S.ZO-1 and Cx43 were co-localized at the intercalated disk.ZO-1 was redistributed in the lateralization of the membrane and co-localized with Cx43 in group I/R.The incidence of ZO-1 lateralization was significantly decreased in group S.Conclusion The mechanism by which sevoflurane preconditioning decreases reperfusion arrhythmia is related to inhibition of down-regulation of expression and redistribution of ZO-1 and inhibition of redistribution of Cx43 in rats.

Objective To investigate the epidemiology of viral infection in elderly patients to contract acute exacerbations of chronic obstructive pulmonary disease (AECOPD)in Minhang district of Shanghai from 2010 to 2012,and to study the relationships between viral infection and clinical features.Methods The elderly patients (age >70 year old)with AECOPD admitted from September 2010 to November 2012 were enrolled for study.The patients who couldn't complete lung function test were excluded.The pharyngeal swabs (PS)were taken from each patient within the first 24 h after admission.Nine respiratory viruses and their subtypes from pharyngeal swabs were detected by the nested multiplex polymerase chain reaction (PCR)method,including influenza virus A (FluA),2009 influenza A (H1N1 )virus (09FluH1 ), influenza virus B (FluB),respiratory syncytial virus A (RSVA)and B (RSVB),human coronavirus-229E (hCOV-229E),human coronavirus-NL63 (hCOV-NL63 ),human coronavirus-OC43 (hCOV-OC43 ), human coronavirus-HKU1 (hCOV-HKU1),human parainfluenza virus 1-4 (hPIV1-4),human adenovirus (hAdV),human boca virus (hBoV),human metapneumo-virus (hMPV)and human rhinovirus (hRV). According to the PCR results,all patients were divided into positive viral infection group and negative viral infection group.The relationships between viral infection and clinical features were analyzed.Results Sixty patients were eligible for study.Of them,14 patients were found to be positive for virus infection including a triple infected patient (FluB,hRV and hROV)and 46 patients were negative for virus infection.The viral pathogens detected in the positive viral group were:9 cases of hRV (15.00%),2 cases of hPIV (3.33%),2 cases of hCOV (3.33%),2 cases of FluB (3.33%)and 1 cases of RSV (1.67%).The mortality in the positive viral group was higher than that in the negative viral group.However,the other clinical characteristics between the two groups had no significant differences. Conclusions Human rhinovirus was the most common viral pathogen in elderly patients with AECOPD.Viral infection might be associated with the prognosis.However,the patients with viral infection are lack of specific clinical characteristics,therefore,the prompt diagnosis before careful study would be difficult.

Objective To evaluate the relationship between calmodulin protein kinase Ⅱ (CaMK Ⅱ) and levosimendan against arrhythmias induced by myocardial ischemia-reperfusion (I/R) in rats in vitro.Methods Thirty male Wistar rats,weighing 250-300 g,were randomly divided into 3 groups (n =10 each) using a random number table:control group (group C),I/R group and levosimendan group (group L).Their hearts were rapidly excised and perfused in a langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 36.5-37.5 ℃.At 20 min of equilibration,the hearts were perfused with K-H solution for 60 min in group C.The hearts were subjected to 30 min of ischemia followed by 30 min reperfusion with K-H solution in group I/R.The hearts were subjected to 30 min of ischemia followed by 30 min reperfusion with K-H solution containing 300 nmol/L levosimendan in group L.Left ventricle developed pressure (LVDP),left ventricle end-diastolic pressure (LVEDP),+ dP/dt-dP/dtmax and heart rate (HR) were recorded immediately before ischemia and at 15 and 30 min of reperfusion.Arrhythmia was recorded during reperfusion and scored.Specimens were obtained from the apex of heart at 30 min of reperfusion for determination of the intracellular calcium concentration ([Ca2 +] i).Myocardial specimens were obtained from the left ventricle at 30 min of reperfusion to detect CaMK Ⅱ activity.Results Compared with group C,arrhythmia score,[Ca2+]i and CaMK [Ⅱ activity were significantly increased,and LVDP,+ dP/dtmax,-dP/dtmax and HR were decreased,and LVEDP was increased at 15 and 30 min of reperfusion in group I/R.Compared with group I/R,the number of ventricular premature beat,arrhythmia score,[Ca2+] i and CaMK Ⅱ activity were significantly decreased,and LVDP,+ dP/dtmax,-dP/dtmax and HR were increased,and LVEDP was decreased at 15 and 30 min of reperfusion in group L.Conclusion Inhibition of CaMK Ⅱ activity is involved in the mechanism by which levosimendan decreases the development of arrhythmias induced by myocardial I/R in rats.

This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was
12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .

ObjectiveTo investigate the protective effect of sevoflurane postconditioning (Sevo-Postcon)on the hearts isolated from rats with diabetes mellitus (DM) of different duration against ischemia-reperfusion (I/R)injury.MethodsSeventy-two pathogen-free male SD rats weighing 200-240 g were randomly divided into 3 groups ( n =24 each):group Ⅰ rats without DM (C) ; group Ⅱ rats with 2 week DM (2w DM) and group Ⅲ rats with 6 week DM (6w DM).DM was produced by intraperitoneal (IP) 1％ streptozocin (STZ) 60 mg/kg and confirmed by fasting blood glucose concentration ＞ 16.7 mmol/L in groups Ⅱ and Ⅲ.Hearts were isolated from rats and perfused with Krebs-Henseleit buffer (KHB) in a Langendorff apparatus.After a 15 min stabilization period,the isolated hearts were subjected to 30 min of global no-flow ischemia followed by 75 min of reperfusion.Twelve hearts in each group were perfused after ischemia with KHB saturated with 3％ Sevo for 15 min followed by perfusion with regular KHB for 60 min.LVEDP,LVDP, ± dp/dt and HR were measured and recorded after 15 min stabilization (T0,baseline) and at 15 and 75 min of reperfusion (T1,2 ).Myocardial specimens were obtained at 15 min of reperfusion (T1) for detection of p-Akt expression (by Western blot analysis).Infarct size was determined at 75 min of reperfusion (T2).ResultsSevo-Postcon significantly improved cardiac function,reduced infarct size and up-regulated p-Akt expression in groups Ⅰ (C) and Ⅱ (2w DM),while in group Ⅲ (6w DM) Sevo-Postcon did not cause any change in cardiac function,infarct size and p-Akt expression as compared with the isolated hearts without Sevo-Postcon.ConclusionThe cardioprotective effect of Sevo-Postcon can be attenuated with increasing duration of DM by impairing PI3K/Akt signaling pathway.