Objective To explore the therapeutic effect and mechanism of electroacupuncture on depressive model mice based on the phosphatase and tensin homolog-induced kinase 1(PINK1)/Parkin pathway.Methods Specific pathogen-free grade male C57BL/6J mice were used.For experiment 1,60 mice were randomly divided into blank,model,sham electroacupuncture,and electroacupuncture groups using the random number table method,with 15 rats per group.For experiment 2,30 mice were randomly divided into normal,cyclosporine A(CsA),and electroacupuncture+CsA groups using the same method,with 10 rats per group.The chronic restraint stress(CRS)was used to establish a depression model.After successful modeling,CRS was continued to maintain model stability.After modeling,1 h before daily CRS stimulation,the electroacupuncture and electroacupuncture+CsA groups received electroacupuncture interventions at the"Baihui"(GV20)and"Zusanli"(ST36)acupoints,using continuous wave stimulation at a frequency of 2 Hz and an intensity of 1 mA for 20 min,once daily for 7 consecutive days.Mice in the sham electroacupuncture group received superficial needling at non-meridian,non-acupoint locations under the axilla 1 h before CRS,with the electroacupuncture device connected but not powered on once a day for 7 consecutive days.Mice in the CsA and electroacupuncture+CsA groups received an intraperitoneal injection of CsA solution(0.2 mg/g)30 min before electroacupuncture intervention,once daily for 7 consecutive days.In experiment 1,depressive-like behavior was assessed using the open field,tail suspension,and sucrose preference tests.The spontaneous excitatory postsynaptic currents(sEPSC)and spontaneous inhibitory postsynaptic currents(sIPSC)parameters of hippocampal neurons were evaluated using brain slice patch clamp techniques.Western blotting was conducted to measure the expression levels of mitochondrial autophagy-related proteins PINK 1,phosphorylated PINK1(p-PINK1),Parkin,microtubule-associated protein 1A/1B-light chain 3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),ubiquitin-binding protein(p62),and mitochondrial markers,including translocase of outer mitochondrial membrane 20(TOMM20),heat shock protein 60(HSP 60),and cytochrome c oxidase Ⅳ(COX Ⅳ).Immunofluorescence was used to detect PINK1 protein expression in the CA3 region of the hippocampus.Transmission electron microscopy was used to examine the ultrastructure of mitochondria in hippocampal neurons.On the basis of experiment 1,experiment 2 evaluated depressive-like behavior in mice using sucrose preference,open field,and tail suspension tests;Western blotting was used to detect the expressions of PINK1,p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,p62,TOMM20,HSP 60,and COX Ⅳ proteins of hippocampus in mice.The mitochondrial ultrastructure was observed in hippocampal neurons using transmission electron microscopy.Results In experiment 1,compared with the blank group,the model and sham electroacupuncture groups exhibited a decrease in sucrose consumption rate,a decrease in the time spent in the center area,a reduced proportion of distance moved in the center area,and an increase in immobility time of tail suspension(P＜0.05).The sEPSC and sIPSC in hippocampal neurons decreased in both amplitude and frequency(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus were reduced,whereas the p62 expression level was increased(P＜0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus decreased(P＜0.05).The number of healthy mitochondria in hippocampal neurons was reduced,with numerous damaged mitochondrial structures observed.Compared to the model and sham electroacupuncture groups,the electroacupuncture group showed an increased in the time spent in the center area,a higher proportion of distance moved in the center area,and an elevated sucrose consumption rate.In contrast,the immobility time in the tail suspension test decreased(P＜0.05),whereas the amplitude and frequency of sEPSC and sIPSC in hippocampal neurons increased(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus increased,whereas the p62 expression level decreased(P＜0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus increased(P＜0.05).Additionally,mitochondrial damage in hippocampal neurons was alleviated,and a notable presence of autophagosomes mitophagy lysosomes was observed.In experiment 2,compared with the normal group,the mice in the CsA and electroacupuncture+CsA groups showed a decrease in the time spent in the center area and the proportion of distance moved in the center area,a decrease in sucrose consumption rate,and an increase in the immobility time in the tail suspension test(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COX Ⅳ expression levels in the hippocampus decreased,whereas p62 expression increased(P＜0.05).Many damaged mitochondria were observed in hippocampal neurons.Conclusion Electroacupuncture may exert its antidepressant effects by promoting PINK1/Parkin pathway-mediated mitophagy to eliminate damaged mitochondria,thereby restoring the function of hippocampal neurons in depressive model mice.

Objective To explore the therapeutic effect and mechanism of electroacupuncture on depressive model mice based on the phosphatase and tensin homolog-induced kinase 1(PINK1)/Parkin pathway.Methods Specific pathogen-free grade male C57BL/6J mice were used.For experiment 1,60 mice were randomly divided into blank,model,sham electroacupuncture,and electroacupuncture groups using the random number table method,with 15 rats per group.For experiment 2,30 mice were randomly divided into normal,cyclosporine A(CsA),and electroacupuncture+CsA groups using the same method,with 10 rats per group.The chronic restraint stress(CRS)was used to establish a depression model.After successful modeling,CRS was continued to maintain model stability.After modeling,1 h before daily CRS stimulation,the electroacupuncture and electroacupuncture+CsA groups received electroacupuncture interventions at the"Baihui"(GV20)and"Zusanli"(ST36)acupoints,using continuous wave stimulation at a frequency of 2 Hz and an intensity of 1 mA for 20 min,once daily for 7 consecutive days.Mice in the sham electroacupuncture group received superficial needling at non-meridian,non-acupoint locations under the axilla 1 h before CRS,with the electroacupuncture device connected but not powered on once a day for 7 consecutive days.Mice in the CsA and electroacupuncture+CsA groups received an intraperitoneal injection of CsA solution(0.2 mg/g)30 min before electroacupuncture intervention,once daily for 7 consecutive days.In experiment 1,depressive-like behavior was assessed using the open field,tail suspension,and sucrose preference tests.The spontaneous excitatory postsynaptic currents(sEPSC)and spontaneous inhibitory postsynaptic currents(sIPSC)parameters of hippocampal neurons were evaluated using brain slice patch clamp techniques.Western blotting was conducted to measure the expression levels of mitochondrial autophagy-related proteins PINK 1,phosphorylated PINK1(p-PINK1),Parkin,microtubule-associated protein 1A/1B-light chain 3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),ubiquitin-binding protein(p62),and mitochondrial markers,including translocase of outer mitochondrial membrane 20(TOMM20),heat shock protein 60(HSP 60),and cytochrome c oxidase Ⅳ(COX Ⅳ).Immunofluorescence was used to detect PINK1 protein expression in the CA3 region of the hippocampus.Transmission electron microscopy was used to examine the ultrastructure of mitochondria in hippocampal neurons.On the basis of experiment 1,experiment 2 evaluated depressive-like behavior in mice using sucrose preference,open field,and tail suspension tests;Western blotting was used to detect the expressions of PINK1,p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,p62,TOMM20,HSP 60,and COX Ⅳ proteins of hippocampus in mice.The mitochondrial ultrastructure was observed in hippocampal neurons using transmission electron microscopy.Results In experiment 1,compared with the blank group,the model and sham electroacupuncture groups exhibited a decrease in sucrose consumption rate,a decrease in the time spent in the center area,a reduced proportion of distance moved in the center area,and an increase in immobility time of tail suspension(P＜0.05).The sEPSC and sIPSC in hippocampal neurons decreased in both amplitude and frequency(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus were reduced,whereas the p62 expression level was increased(P＜0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus decreased(P＜0.05).The number of healthy mitochondria in hippocampal neurons was reduced,with numerous damaged mitochondrial structures observed.Compared to the model and sham electroacupuncture groups,the electroacupuncture group showed an increased in the time spent in the center area,a higher proportion of distance moved in the center area,and an elevated sucrose consumption rate.In contrast,the immobility time in the tail suspension test decreased(P＜0.05),whereas the amplitude and frequency of sEPSC and sIPSC in hippocampal neurons increased(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus increased,whereas the p62 expression level decreased(P＜0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus increased(P＜0.05).Additionally,mitochondrial damage in hippocampal neurons was alleviated,and a notable presence of autophagosomes mitophagy lysosomes was observed.In experiment 2,compared with the normal group,the mice in the CsA and electroacupuncture+CsA groups showed a decrease in the time spent in the center area and the proportion of distance moved in the center area,a decrease in sucrose consumption rate,and an increase in the immobility time in the tail suspension test(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COX Ⅳ expression levels in the hippocampus decreased,whereas p62 expression increased(P＜0.05).Many damaged mitochondria were observed in hippocampal neurons.Conclusion Electroacupuncture may exert its antidepressant effects by promoting PINK1/Parkin pathway-mediated mitophagy to eliminate damaged mitochondria,thereby restoring the function of hippocampal neurons in depressive model mice.

ObjectiveTo explore the relationship between smoking behavior and related factors among the adult residents in Fengxian District,so as to provide an evidence for carrying out tobacco control and other health promotion work. MethodsA multi-stage stratified cluster random sampling method was used to select 2 272 community residents aged between 15 and 69 yeas to carry out the questionnaire survey. ResultsIn 2020, the smoking rate of adult residents in Fengxian District was 23.50%. Smoking behavior was statistically correlated with age, gender, household registration, chronic disease, occupation and educational level. Smoking behavior was inversely correlated with educational level. Smoking rate of male residents was significantly higher than that of female residents, smoking rate of residents with chronic diseases was significantly higher than that of those without suffering from chronic diseases, and smoking rate of permanent registered residents was significantly higher than that of those non-locals. The highest smoking prevalence was among retired and freelancers, followed by staff of government agencies and public institutes, while the lowest was among students, followed by intellectuals. Multivariate logistic regression analysis showed that gender, age and education level were the main factors affecting the smoking prevalence level. ConclusionThe general　smoking rate of adult residents in Fengxian District was higher than the average level in Shanghai but lower than the national level. Male residents aged ≥25 years and with lower education level are the key invention targets for tobacco control.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Objective:To explore the diagnostic value of laparoscopy in the postoperative recurrence of peritoneal metastasis in gastric cancer, and to investigate the efficacy of bidirectional intraperitoneal and systemic (BIPS) chemotherapy for the recurrence.Methods:The descriptive case series study was conducted. Case inclusion criteria: (1) gastric cancer patients without synchronous distant metastasis received D2 radical gastrectomy; (2) postoperative adjuvant chemotherapy was administered; (3) no other distant metastasis except recurrence of peritoneal metastasis; (4) age of 18-75 years; (5) Eastern Cooperative Oncology Group (ECOG) performance-status score≤2; (6) pretreatment evaluation suggested that surgery and chemotherapy could be tolerated. Eight consecutive gastric cancer patients with postoperative recurrence of peritoneal metastasis who met the above criteria at Department of Gastrointestinal Surgery of Ruijin Hospital from September 2015 to September 2016 were enrolled into the study. There were 6 males and 2 females with the median age of 52 (38-68) years. They received laparoscopy or laparotomy first, and then were evaluated with reference to the Sugarbaker peritoneal cancer index (PCI) and the peritoneal metastasis classification of gastric cancer developed by the Japanese Gastric Cancer Research Association. A peritoneal access port was implanted in the subcutaneous space of the lower abdomen and the patients received chemotherapy for 21 days as a course of treatment. All the patients received intraperitoneal 20 mg/m 2 of paclitaxel (PTX) via implanted subcutaneous peritoneal access ports and intravenous 50 mg/m 2 of PTX at day 1 and day 8, meanwhile 80 mg/m 2 of Tigio was orally administered per day for 14 consecutive days, followed by 7 days of interval. Follow-up ended on December 15, 2019. Results:Of these 8 patients with recurrence of peritoneal metastasis after gastric cancer surgery, 1 case underwent laparotomy and loop stoma of terminal ileum because of complete colonic obstruction, and the remaining 7 cases underwent laparoscopy successfully and the recurrence of peritoneal metastasis was clearly diagnosed. Two patients with ovarian metastasis underwent laparoscopic bilateral adnexectomy. The median follow-up time was 17.5 (1.5 to 39.0) months, the median number of BIPS chemotherapy course was 11 (1 to 30), and the median survival time (MST) after BIPS chemotherapy was 17.0 months. The major adverse reaction in BIPS treatment was mainly myelosuppression, of which grade 3/4 leukopenia and neutropenia developed in 1 and 2 cases respectively. No BIPS-related death occurred. The MST of gastric cancer after radical gastrectomy was 40.0 months.Conclusions:Laparoscopy is a safe and feasible method for diagnosing the recurrence of peritoneal metastasis of gastric cancer. BIPS chemotherapy is effective and safe for its treatment and deserves further study.

Objective:To explore the diagnostic value of laparoscopy in the postoperative recurrence of peritoneal metastasis in gastric cancer, and to investigate the efficacy of bidirectional intraperitoneal and systemic (BIPS) chemotherapy for the recurrence.Methods:The descriptive case series study was conducted. Case inclusion criteria: (1) gastric cancer patients without synchronous distant metastasis received D2 radical gastrectomy; (2) postoperative adjuvant chemotherapy was administered; (3) no other distant metastasis except recurrence of peritoneal metastasis; (4) age of 18-75 years; (5) Eastern Cooperative Oncology Group (ECOG) performance-status score≤2; (6) pretreatment evaluation suggested that surgery and chemotherapy could be tolerated. Eight consecutive gastric cancer patients with postoperative recurrence of peritoneal metastasis who met the above criteria at Department of Gastrointestinal Surgery of Ruijin Hospital from September 2015 to September 2016 were enrolled into the study. There were 6 males and 2 females with the median age of 52 (38-68) years. They received laparoscopy or laparotomy first, and then were evaluated with reference to the Sugarbaker peritoneal cancer index (PCI) and the peritoneal metastasis classification of gastric cancer developed by the Japanese Gastric Cancer Research Association. A peritoneal access port was implanted in the subcutaneous space of the lower abdomen and the patients received chemotherapy for 21 days as a course of treatment. All the patients received intraperitoneal 20 mg/m 2 of paclitaxel (PTX) via implanted subcutaneous peritoneal access ports and intravenous 50 mg/m 2 of PTX at day 1 and day 8, meanwhile 80 mg/m 2 of Tigio was orally administered per day for 14 consecutive days, followed by 7 days of interval. Follow-up ended on December 15, 2019. Results:Of these 8 patients with recurrence of peritoneal metastasis after gastric cancer surgery, 1 case underwent laparotomy and loop stoma of terminal ileum because of complete colonic obstruction, and the remaining 7 cases underwent laparoscopy successfully and the recurrence of peritoneal metastasis was clearly diagnosed. Two patients with ovarian metastasis underwent laparoscopic bilateral adnexectomy. The median follow-up time was 17.5 (1.5 to 39.0) months, the median number of BIPS chemotherapy course was 11 (1 to 30), and the median survival time (MST) after BIPS chemotherapy was 17.0 months. The major adverse reaction in BIPS treatment was mainly myelosuppression, of which grade 3/4 leukopenia and neutropenia developed in 1 and 2 cases respectively. No BIPS-related death occurred. The MST of gastric cancer after radical gastrectomy was 40.0 months.Conclusions:Laparoscopy is a safe and feasible method for diagnosing the recurrence of peritoneal metastasis of gastric cancer. BIPS chemotherapy is effective and safe for its treatment and deserves further study.

Objective: To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) among sonographers in a province of China and influencing factors for WMSDs, and to provide a practical basis for the prevention and treatment of WMSDs in sonographers. Methods: From November 2016 to February 2017, stratified cluster sampling was used to select 700 sonographers from 50 hospitals in this province. A self-designed questionnaire for WMSDs in sonographers was used to investigate general data and the prevalence of WMSDs, and the influencing factors for the prevalence of WMSDs were analyzed. Results: The prevalence rate of WMSDs among these sonographers was 80.22%, and the prevalence rates of WMSDs in the shoulder, the neck, the waist, the back, the wrist, the elbow, the hip, the knee, and the ankle were 74.55%, 68.87%, 63.44%, 57.26%, 53.16%, 45.22%, 37.88%, 30.44%, and 29.24%, respectively. There was a significant difference in the prevalence rate of WMSDs between the sonographers with different ages and working years, and the prevalence rate of WMSDs tended to increase with the increase in age and working years (χ²=20.86 and 18.52, P<0.01) . The multivariate logistic regression analysis showed that female sex (odds ratio [OR]=1.798) , working years >16 (OR=1.004) , weekly working hours >40 (OR=1.616) , poor physical conditions (OR=1.690) , and high work fatigue (OR=1.302) were risk factors for WMSDs in sonographers. Conclusion There are high prevalence rates of WMSDs in the shoulder, the neck, the waist, the back, the wrist, and the elbow. Sonographers should strengthen self-protection awareness, and effective preventive measures should be adopted to reduce the prevalence rate of WMSDs.

Mass spectrometry and database searching are necessary to identify proteins and peptides. With the rapid development of mass spectrometry technology, mass spectrometry data in proteomics are acquired very quickly, providing a powerful method to identify large-scale proteins and peptides, making mass spectrometry data-based proteomics research more and more into the mainstream. The traditional database searching method has many limitations to identify post-translational modifications of peptides. This paper systematically reviews the development, theoretical concept and applications of spectral network method, and the advantages of spectral network library to identify peptides.

OBJECTIVETo identify potential mutation in a Chinese family affected with Charcot-Marie-Tooth disease(CMT).

METHODSClinical data of the family was collected, and genomic DNA was extracted from peripheral blood samples of the family members. Seventy-two candidate genes of the proband were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The protein structure was predicted with PyMOL-1 software.

RESULTSA homozygous missense mutation c.1894G>A(p.E632K) was identified in the exon 11 of the SH3TC2 gene in the proband. Heterozygous c.1894G>A mutation was also detected in the proband's father, mother and daughter, but not in the healthy family members and 300 normal controls. Retrieval of the NCBI, HGMD and 1000 genome databases has verified the c.1894G>A to be as a novel mutation. Computer simulation has suggested that the mutation has altered the 3D structure of the SH3TC2 protein.

CONCLUSIONThe proband was diagnosed as CMT4C, for which the underlying gene was SH3TC2. This finding has expanded the spectrum of SH3TC2 mutation in association with CMT4C.

Adult ; Aged ; Base Sequence ; Charcot-Marie-Tooth Disease ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; Models, Molecular ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Proteins ; genetics ; Young Adult

Objective To explore the multi-modal MRI characteristics of breast cancers in dense breasts.Methods 120 patients with breast cancer shown on mammography underwent breast MRI,which were solitary and confirmed by pathological examination. According to the BI-RADS classification of breast,the 120 cases were divided into two groups including dense type breast and non-dense type one.The differences in morphological features,ADC values (b=1 000 s/mm2 )and time-signal intensity curve (TIC)of the lesions between two groups were analyzed and compared.Statistical analysis was performed using SPSS1 6.0.Results The breast cancers in dense breast were vulnerable to have a spiculated margin (44/68 in the dense breast group vs.1 6/52 in the non-dense breast group,P =0.000).The size of the lesion in dense breast (1.83 ±0.98)cm was bigger than that in non-dense breast (1.40±0.46)cm (P =0.005).The non-mass-like enhancement of the lesion in dense breast was much more than that in non-dense breast (P =0.000).In addition,the average ADC values of the lesion in dense breast (0.89±0.12)×10 -3 mm2/s were lower than in non-dense breast (0.95±0.10)×10 -3 mm2/s(P =0.01 6).Conclusion The breast cancer in the dense breast has different MRI findings in comparison with non-dense breast.