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.

Respiratory syncytial virus(RSV)is a major cause of severe lower respiratory disease and can infect all populations,posing a significant health threat to infants and the elderly.After more than 60 years of research,there are only 2 RSV vaccines and 2 preventive monoclonal antibodies be licensed,but the use of the population is severely limited,expensive and difficult to large-scale popularization.RSV vaccine development faces a number of obstacles,such as the lack of animal models,avoidance of RSV immunity,and short duration of immunity.Since the failure of formalin inactivated RSV vaccine trials,RSV vaccine development has become more cautious and difficult.This article briefly reviews the research status of RSV vaccines,and introduces several representative vaccines currently under development,in order to facilitate researchers to review the latest progress and contribute to promoting vaccine research.

Respiratory syncytial virus(RSV)is a major cause of severe lower respiratory disease and can infect all populations,posing a significant health threat to infants and the elderly.After more than 60 years of research,there are only 2 RSV vaccines and 2 preventive monoclonal antibodies be licensed,but the use of the population is severely limited,expensive and difficult to large-scale popularization.RSV vaccine development faces a number of obstacles,such as the lack of animal models,avoidance of RSV immunity,and short duration of immunity.Since the failure of formalin inactivated RSV vaccine trials,RSV vaccine development has become more cautious and difficult.This article briefly reviews the research status of RSV vaccines,and introduces several representative vaccines currently under development,in order to facilitate researchers to review the latest progress and contribute to promoting vaccine research.

Objective:To evaluate the effects of intrathecal infusion chemotherapy on intracranial pressure (ICP) in non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM) by ultrasound measurement of the optic nerve beside the bed of optic nerve sheath diameter (ONSD) .Methods:A total of 31 NSCLC-LM patients who underwent intrathecal infusion chemotherapy at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from June 10, 2021 to December 25, 2022 were collected. The ONSD values were measured before and after the first lumbar puncture by bedside optic nerve ultrasound, and measured dynamically 30 min before intrathecal infusion chemotherapy (T0) , 30 min (T1) , 1 h (T2) , 2 h (T3) , 4 h (T4) , 6 h (T5) , and 24 h (T6) after intrathecal infusion chemotherapy. ICP ONSD was calculated, with differences between ICP LP and ICP ONSD, and differences between ONSD and ICP ONSD series at different time being compared separately. Mean arterial pressure (MAP) , heart rate, and headache score were assessed and compared respectively at T0, T1, T2, T3, T4, T5 and T6. Spearman analysis was used to evaluate the correlation between the response assessment in neuro-oncology (RANO) score and ICP. Results:Before the first lumbar puncture for cerebrospinal fluid drainage, ICP LP was (218.55±63.83) mmH 2O, left eye, right eye, and binocular eyes ICP ONSD were (217.28±57.17) mmH 2O, (223.64±51.13) mmH 2O, and (220.46±52.50) mmH 2O respectively, in NSCLC-LM patients, with no statistically significant difference ( F=0.77, P=0.463) . After first lumbar puncture for cerebrospinal fluid drainage, ICP LP was (214.68±58.01) mmH 2O, left eye, right eye, and binocular eyes ICP ONSD were (216.71±48.96) mmH 2O, (216.62±47.18) mmH 2O, and (216.67±47.86) mmH 2O respectively, with no statistically significant difference ( F=0.12, P=0.757) . At T0, T1, T2, T3, T4, T5, and T6, the MAP during intrathecal infusion chemotherapy was 89.80 (83.40, 93.67) mmHg, 95.00 (80.83, 99.37) mmHg, 91.86 (79.88, 100.14) mmHg, 90.15 (79.04, 100.55) mmHg, 105.14 (88.55, 114.74) mmHg, 98.96 (81.72, 111.81) mmHg, and 89.29 (85.45, 100.38) mmHg, with a statistically significant difference ( χ2=16.11, P=0.013) ; heart rates were 80.00 (75.00, 84.50) times/min, 80.00 (72.50, 87.50) times/min, 74.00 (66.00, 87.50) times/min, 82.00 (72.00, 90.00) times/min, 80.00 (70.50, 90.00) times/min, 77.00 (68.00, 91.00) times/min, 77.00 (71.50, 88.50) times/min, with no statistically significant difference ( χ2=2.18, P=0.902) ; headache scores were 2.00 (0.50, 3.00) score, 2.00 (1.00, 3.00) score, 2.00 (2.00, 3.00) score, 2.00 (1.00, 3.00) score, 2.00 (1.00, 2.00) score, 2.00 (1.00, 2.00) score, and 2.00 (0.00, 2.00) score, with no statistically significant difference ( χ2=11.64, P=0.071) . At T0, T1, T2, T3, T4, T5, and T6, left eye, right eye, and binocular ONSD were (5.85±0.64) mm, (5.72±0.68) mm, (7.11±1.11) mm, (6.42±0.78) mm, (5.69±0.63) mm, (5.61±0.64) mm, (5.65±0.88) mm, (5.85±0.12) mm, (5.89±0.12) mm, (6.93±0.20) mm, (6.40±0.14) mm, (5.71±0.12) mm, (5.66±0.12) mm, (5.33±0.14) mm, (5.85±0.64) mm, (5.81±0.64) mm, (7.02±1.03) mm, (6.41±0.75) mm, (5.70±0.63) mm, (5.64±0.63) mm, (5.49±0.76) mm, with statistically significant differences ( F=58.48, P<0.001; F=49.34, P<0.001; F=78.05, P<0.001) ; ICP ONSD were (222.81±56.81) mmH 2O, (211.89±60.29) mmH 2O, (335.12±98.32) mmH 2O, (274.17±68.87) mmH 2O, (208.77±56.12) mmH 2O, (201.75±56.79) mmH 2O, (205.59±78.36) mmH 2O, (223.26±58.33) mmH 2O, (227.08±61.68) mmH 2O, (319.36±101.10) mmH 2O, (272.33±69.61) mmH 2O, (211.21±57.73) mmH 2O, (206.51±57.22) mmH 2O, (177.22±68.98) mmH 2O, (223.03±57.24) mmH 2O, (219.49±57.24) mmH 2O, (327.24±91.56) mmH 2O, (273.25±67.04) mmH 2O, (209.99±56.26) mmH 2O, (204.13±56.29) mmH 2O, (191.40±67.95) mmH 2O, with statistically significant differences ( F=58.48, P<0.001; F=49.34, P<0.001; F=78.13, P<0.001) . The ONSD of the left eye, right eye, and binocular eyes and the corresponding ICP ONSD increased significantly at T2 compared with T0, T1, T3, T4, T5, and T6, with statistically significant differences (all P<0.05) . Pre- and post-treatment RANO scores were 4.00 (3.00, 7.00) score and 3.00 (2.00, 6.00) score respectively. Pre- and post-treatment RANO scores were positively correlated with ICP ONSD in the left eye ( r=0.55, P=0.001; r=0.60, P<0.001) , right eye ( r=0.54, P=0.001; r=0.46, P=0.009) and binocular eyes ICP ONSD ( r=0.45, P=0.010; r=0.37, P=0.043) . Conclusion:Intrathecal infusion chemotherapy for NSCLC-LM patients can cause a transient increase in ONSD and ICP, with the greatest effect at 1 hour after intrathecal infusion chemotherapy. RANO score is positively correlated with ICP ONSD before and after treatment, which can provide an important reference for evaluating the efficacy of intrathecal infusion chemotherapy.

Druggability is crucial in pharmaceutical drug development as the source of drug research. Druggability research will face greater challenges because Chinese materia medica (CMM) is the multicomponent drug. In this paper, ideas and methods of study on CMM druggability were mainly proposed in combination with the chemical material basis of muticomponents of CMM.

Objective To develop a rapid kit applied to the field for detection of antibody to schistosome in human sera. Methods A new kit for rapid detection of antibody to schistosome was developed through improving the dot immunogold filtration assay (DIGFA). A total of 100 cases of sera from chronic schistosomiasis patients and 140 from healthy people, HBV patients and the people infected with other parasites were detected by the kit. The sensitivity, specificity, Youden's index and Kappa value were utilized as the evaluation standard. Results The sensitivity of detecting antibody to schistosome, specificity, Youden's index and Kappa value were 92% , 95.08% , 0.87 and 0.87, respectively. The cross reaction to patients with clonorchiasis was 5%. Conclusion DICFA kit is practical for antibody to schistosome detection in the field because of its advantages such as smaller serum needed and faster in reaction.