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OBJECTIVE To establish the project approval evaluation system for traditional Chinese medicine （TCM） preparations in medical institutions guided by new drug conversion， to improve the success rate of approval for TCM preparations in medical institutions and lay the foundation for the later drug conversion. METHODS Research and development team used the literature research method and brainstorming method to list and organize relevant elements of project evaluation and determine the initial indicator system. Experts were consulted using the Delphi method to confirm the evaluation index. The weights were calculated based on the proportion of importance scores for each indicator and assigned specific scores to each item. The indicator system was used to evaluate 31 TCM preparations applied for filing by various departments of our hospital from April to July 2023. RESULTS After two rounds of 17 experts’ consultation， the final TCM preparation system included five primary indicators， i.e. theoretical basis， clinical research foundation， pharmaceutical foundation， prescription， and clinical value， as well as 17 secondary indicators including prescription source， traditional Chinese medicine theory， clinical positioning and so on. Human experience was considered as the item which would be rejected as one vote. Based on the above indicator system， our hospital further improved the filing and project approval process for TCM preparations in medical institutions. Among the 31 TCM preparations applied for filing by various departments from April to July 2023， 8 TCM preparations with a score ≥65 were selected for development. CONCLUSIONS The evaluation system is objective， comprehensive， and highly operable. It is suitable for the selection of TCM preparations in medical institutions before research and development.
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AIM: To observe the multimodal imaging characteristics of Best vitelliform macular dystrophy(BVMD).METHODS:The clinical data of 30 patients(60 eyes)diagnosed as BVMD at stage Ⅰ to Ⅳ in Nanjing Medical University Affiliated Eye Hospital from June 2016 to October 2022 were collected for a retrospective analysis, and all patients are binocular involved. All patients underwent best corrected visual acuity(BCVA), slit lamp microscopy, indirect ophthalmoscopy, intraocular pressure, fundus photography, spectral-domain optical coherence tomography(SD-OCT), fundus autofluorescence(FAF), fundus fluorescein angiography(FFA), electro-oculogram(EOG)and optical coherence tomography angiography(OCTA).RESULTS: A total of 30 patients(60 eyes)were included, with 8 eyes at stage Ⅰ, 24 eyes at stage Ⅱ, 22 eyes at stage Ⅲ and 6 eyes at stage Ⅵ. The imaging characteristics of fundus photography, FAF, FFA and SD-OCT were basically consistent with previous literature reports. EOG showed Arden ratio <1.55. OCTA could detect early lesions, observe the location of vitelliform substance, external segment of photoreceptor, fluid and choroidal neovascularization(CNV).CONCLUSION: Multimodal imaging assisted in diagnosing BVMD, reducing missed diagnosis and misdiagnosis, among which OCTA had significant advantages over other examinations, and fast and non-invasive were its biggest advantages.
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Malignant tumors have surpassed stroke and coronary heart disease to become the main cause of death before the age of 70 in the world. The incidence of malignant tumors is increasing year by year， which seriously affects the living standards and social and economic development of Chinese people. Surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy are the main means of Western medicine to intervene in tumors， which are of great significance for prolonging the survival time of patients. However， there are many disadvantages such as adverse reactions and drug resistance. Traditional Chinese medicine has become a research hotspot in recent years because of its definite curative effect and wide application in tumor treatment. Xiao Chaihutang is derived from the Treatise on Febrile and Miscellaneous Diseases. It is composed of Bupleuri Radix， Scutellariae Radix， Ginseng Radix， Pinelliae Rhizoma， Glycyrrhizae Preparata Radix， Ginger， and Jujube. It has the effects of reconciling Shaoyang， reconciling cold and heat Yin and Yang， soothing the liver， and relieving depression. This prescription and the prescriptions based on it are widely used in various stages of tumors. This study summarized the Chinese and foreign research of Xiao Chaihutang in the field of tumors in the past 10 years and explored the role and mechanism of Xiao Chaihutang in blocking precancerous lesions， controlling the development of malignant tumors， reducing the occurrence of adverse reactions after intervention， and alleviating common complications， with a view to expanding the clinical medication ideas.
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Objective To investigate the expression level and diagnostic value of serum DNA polymerase α(DNA pol α)in Alzheimer's disease(AD),and analyze its diagnostic efficacy in AD.Methods A total of 100 patients of dementia of Alzheimer's type(DAT)and 43 patients of mild cognitive impairment(MCI)from Xuanwu Hospital Capital Medical University from March 2019 to April 2023 were included in this study,and 68 healthy individuals of the same age group were collected as the HC group.The expression level of DNA pol α was detected in each group,and the diagnostic value of DNA pol α in AD was analyzed by receiver oper-ating characteristic(ROC)curve.Results The expression level of DNA pol α in DAT group was higher than those in the MCI group(P＜0.05)and the HC group(P＜0.001).The expression level of DNA pol α showed an increasing trend as AD progressed.The expression level of DNA pol α was negatively correlated with Mini Intelligent Mental State Examination Scale(MMSE)score and Montreal Cognitive Assessment Scale(MoCA)score(r=-0.155 3,-0.203 7,P＜0.05).The area under the curve(AUC)of DNA pol α for diagnosing DAT was 0.682,and the sensitivity was 0.900.The AUC for diagnosing MCI was 0.546,and the sensitivity was 0.977.The AUC for differential diagnosis of MCI and DAT was 0.664,the sensitivity was 0.780,and the specificity was 0.535.Conclusion The expression level of DNA pol α is significantly increased in AD patients with DAT,and its expression level is related to the progression of AD,suggesting that DNA pol α has the pos-sibility to be a potential blood biomarker for the diagnosis of AD.
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Objective To study the effect of NAD(P)H:quinone oxidoreductase 1(NQO1)expression lev-el on prognosis in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Methods A total of 103 patients with HBV-HCC underwent surgical treatment in Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine from March 2019 to January 2020 were enrolled.The cancer tissue and adjacent normal tissues were extracted during surgery.Immunohistochemical staining was used to detect the expression of NQO1 in tissues.The clinical and pathological data of patients were collected,and the rela-tionships between high and low expression of NQO1 and pathological characteristics were discussed.A 3-year follow-up was conducted,and the Kaplan-Meier survival curve was drawn and Log-rank test was conducted on median survival time.Then COX model analysis was used to analyze the factors affecting the prognosis of HBV-HCC patients.Results The positive rate of NQO1 in HBV-HCC tissues was 84.47％(87/103)and the high expression rate was 59.22％(61/103).The positive rate and the high expression rate of NQO1 in HBV-HCC tissues were higher than those in adjacent normal tissues(P＜0.05).There were statistically significant differences in tumor maximum diameter,number of lesions,American Joint Committee on Cancer(AJCC)staging,and vascular invasion between patients with high and low expression of NQO1(P＜0.05).The 3-year follow-up results denoted that the median survival time of patients was 37 months,and no cases were lost in follow-up.Among 103 patients,there were 34 dead cases with an overall survival rate of 66.99％(69/103)and 42 recurrence cases with a recurrence-free survival rate of 59.23％(61/103).Kaplan-Meier survival curve re-sults showed that the overall survival rate and recurrence-free survival rate were 52.46％(32/61)and 50.82％(31/61)in NQO1 high expression group,which were lower than 88.10％(37/42)and 71.43％(30/42)in NQO1 low expression group(P＜0.05).COX model analysis results showed that high expression of NQO1,tumor maximum diameter ≥5 cm,multiple lesions,AJCC stage Ⅲ to Ⅳ and vascular invasion were independ-ent risk factors for prognosis(P＜0.05).Conclusion NQO1 is highly expressed in HBV-HCC tissue,and is related to the clinicopathological characteristics of patients,so it could be used as an independent biomarker for evaluating prognosis.
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Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.
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Acute kidney injury(AKI)is a global public health problem with high morbidity,high mortality and costly treatment cost.The pathogenesis of AKI is very complex,and the treatment strategies for AKI are lim-ited,then it is very matter to explore the pathophysiological mechanism and potential therapeutic targets of acute kidney injury.N6-methyladenosine(m6A)is the most abundant and extremely conservative epigenetic modification in eukaryotic,which is a dynamic and reversible process involving in splicing,nuclear export,translation,stabil-ity,and higher structure of RNA,and regulated by three regulatory factors:methyltransferase,demethylase and methylated reading protein.Current studies have found that m6A plays an important regulatory role in AKI and can be a potential therapeutic target for AKI.In this review,we provide a brief description of m6A and summarize the impact of m6A on AKI and possible future study directions for this research.
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Overweight/obesity has become an increasingly serious global public health problem. Studies have shown that many factors caused by overweight/obesity are involved in the occurrence of atherosclerosis, including adipokines, inflammatory factors and overweight/obesity related metabolic syndrome. This paper reviews the research progress on overweight/obesity and atherosclerosis from the above perspectives, aiming to provide reference for the prevention of overweight/obesity-related atherosclerosis.
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AIM: To observe the distribution of cone in the macular of healthy adult in different ages using adaptive optics scanning laser ophthalmoscope(AO-SLO)system, and analyze its relationship with age.METHODS: A total of 100 healthy examinees(200 eyes)in our hospital from June to July 2023 were selected, and they were divided into four groups according to their age, with 25 cases(50 eyes)in each group, including 18-30 years in group A, 31-40 years in group B, 41-50 years in group C, 51-65 years in group D. AO-SLO was performed in both eyes and cone density was measured.RESULTS: The density of cone in the foveal eccentricity of 3° and 2.4°×2.4° in each group was different(P<0.001), and the cone density in each area showed a relatively regular distribution characteristics, with the highest density in the temporal side, and the temporal>nasal>inferior>superior sides from high to low. The mean cone density in the macular area of both eyes was 14 144.38±1 082.40, 13 241.24±535.32, 12 930.29±727.73, and 10 907.50±490.86 cell/mm2, respectively(P<0.001), indicating that the cone density decreased with age. The correlation analysis showed that the mean cone density in the macular area was negatively correlated with age(r=-0.578, P<0.001).CONCLUSION: AO-SLO is a quantitative non-invasive detection of cones, and there is a negative correlation between cone density and age in healthy human. Furthermore, density of cone in healthy people over 50 years was significantly decreased.
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Cardiovascular diseases are preventable and controllable, and the disease burden caused by them can be reduced after preventive intervention. Attentions should be paid to the prevention of disease causes. For high-risk population, it is necessary to conduct early screening of cardiovascular diseases, control risk factors, reduce exposure level, prevent and control the occurrence or progression of diseases. Clinical prevention services are to evaluate risk factors of health in clinical sites, which can prevent diseases by personalized intervention measures. Clinical prevention services for high-risk population with cardiovascular diseases are generally at a low level in China. This article reviews the early screening, risk factors and clinical prevention services for high-risk population with cardiovascular diseases.
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BACKGROUND:Immunotherapy enhances the anti-cancer immune response in many ways,so combined immunotherapy is a better choice.Ultrasound-targeted microbubble destruction technique delivers drugs,genes,antibodies and cytokines directly to the cytoplasm of immune cells and enhances the immune response.However,the application of ultrasound-targeted microbubble destruction technique in the treatment of ovarian cancer with both CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody has not been reported. OBJECTIVE:To investigate the effect of ultrasound irradiation on the proliferation and migration of ovarian cancer cells with CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody double targeted nanobubbles. METHODS:IOSE-80 normal ovarian epithelial cells,SKOV3 and CAOV3 ovarian cancer cells were cultured and expanded.Double labeling fluorescence immunoassay was used to co-locate CXC chemokine receptor 4 and programmed death-ligand 1 protein.Western blot assay was used to detect the relative expression of CXC chemokine receptor 4 and programmed death-ligand 1 protein in three kinds of cells and screen out the experimental cells,i.e.,pure nanobubbles,nanobubbles carrying CXC chemokine receptor 4 antibody,nanobubbles carrying CXC chemokine receptor 4 and programmed death-ligand 1 antibody.SKOV3 ovarian cancer cells in the logarithmic growth phase were taken and divided into six groups for treatment.Group A was added with McCoy's 5A medium.Group B was added with McCoy's 5A medium containing stromal cell-derived factor-1.Group C was added with pure nanobubble solution and McCoy's 5A medium containing stromal cell-derived factor-1.Group D was added with nanobubble solution containing CXC chemokine receptor 4 antibody and McCoy's 5A medium containing stromal cell-derived factor-1.Group E was added with nanobubble solution containing CXC chemokine receptor 4 and programmed death-ligand 1 antibody and McCoy's 5A medium containing stromal cell-derived factor-1.Pure nanobubble solution was added in group F.After ultrasonic irradiation for 120 seconds and incubation for 48 hours,the survival rate of cells was measured by CCK-8 assay,and the healing and migration ability of cells in groups B-E were measured by wound healing test. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that CXC chemokine receptor 4 and programmed death-ligand 1 protein could be expressed in all three kinds of cells.Western blot assay showed that the expression levels of CXC chemokine receptor 4 and programmed death-ligand 1 in SKOV3 and CAOV3 ovarian cancer cells were significantly higher than those in IOSE-80 normal ovarian epithelial cells(P<0.05).(2)CCK-8 assay results exhibited that the cell survival rate of group B was higher than that of group A(P<0.05).The cell survival rate of group F was lower than that of group A(P<0.05).The cell survival rate of groups B-E decreased gradually,and there were significant differences between the two groups(P<0.05).(3)Wound healing test demonstrated that the cell healing rate of groups B-E decreased gradually,and there were significant differences between the two groups(P<0.05).(4)The results show that the use of CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody double targeted nanobubbles under ultrasound-targeted microbubble destruction can significantly inhibit the proliferation and migration of ovarian cancer cells.
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Objective To explore the protection effect and mechanism of preoperative ultrasound-guided stellate ganglion block(SGB)on lung in patients undergoing one-lung ventilation(OLV)during thoracoscopic surgery.Methods Eighty-four patients who underwent OLV during thoracoscopic lobectomy at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2021 to April 2022 were selected as research subjects,and the patients were divided into the observation group and control group by using a random number table,with 42 patients in each group.Patients in the observation group received ultrasound-guided SGB before anesthesia induction,while patients in the control group did not undergo puncture procedures.Patients in both groups received the same anesthesia induction and maintenance protocols.Hemodynamic,respiratory and arterial blood gas parameters were recorded at various time points:upon entering the operating room(T0),before OLV(T1),30 minutes after OLV initiation(T2),60 minutes after OLV initiation(T3),completion of surgery(T4),and 30 minutes after extubation(T5).Oxygenation index(OI),intrapulmonary shunt rate(Qs/Qt)and pH values of patients in the two groups were compared at these time points.Venous blood were collected from patients in both groups at T0,T3 and T5,and enzyme-linked immunosorbent assay was employed to measure the levels of surfactant protein-A(SP-A),superoxide dismutase(SOD),malondialdehyde(MDA),interleukin-6(IL-6)and interleukin-10(IL-10).Postoperative SGB-related complications and pulmonary complications within 72 hours were recorded.Results The mean arterial pressure(MAP)and heart rate(HR)in both groups were significantly lower at T,,T2,and T3 compared to T0(P＜0.05);the MAP and HR at T4 and T5 had no statis-tically significant difference compared to those at T0(P＞0.05);there was no significant difference in MAP and HR at other time points(P＞0.05).MAP in the observation group at T1,T2 and T3 was significantly lower than that in the control group(P＜0.05),and HR in the observation group at T2 and T3 was significantly lower than that in the control group(P＜0.05);there were no significant differences in MAP and HR between the two groups at other time points(P＞0.05).There were no significant differences in pulse oxygen saturation(SpO2)between the two groups at T0-T5(P＞0.05).At T2 and T3,peak airway pressure(Ppeak)and respiratory rate(RR)were significantly higher than those at T,and T4,and tidal volume(TV)was significantly lower than that at T,and T4 in both groups(P＜0.05).Ppeak and TV in the observation group at T2 and T3 were significantly lower than those in the control group(P＜0.05);there were no significant differences in Ppeak and TV between the two groups at T1 and T4(P＞0.05).RR and partial pressure of end-tidal carbon dioxide(PetCO2)at T1-T4 showed no significant differences between the two groups(P＞0.05).The pH values at T0-T5 showed no significant differences between the two groups(all P＞0.05).The OI at T,had no significant difference compared to that at T0 in both groups(P＞0.05);OI at T2-T5 in both groups was significantly lower than that at T0(P＜0.05);OI in the observation group at T2-T5 was significantly higher than that in the control group(P＜0.05).Qs/Qt at T2-T5 was significantly higher than that at T0 and T1 in both groups(all P＜0.05);Qs/Qt in the observation group at T2-T5 was significantly lower than that in the control group(P＜0.05).At T3 and T5,serum SP-A and IL-6 levels in both groups were significantly higher than those at T0(P＜0.05);serum SP-A and IL-6 levels in the observation group at T3 and T5 were significantly lower than those in the control group(P＜0.05).At T3 and T5,serum IL-10 level in the control group were significantly lower than that at T0,while serum IL-10 level in the observation group were significantly higher than that at T0(P＜0.05).Serum IL-10 level in the observation group at T3 and T5 were higher than that in the control group(P＜0.05).At T3 and T5,serum MDA level in the control group was significantly higher than that at T0(P＜0.05);serum MDA level in the observation group showed no significant difference compared to that at T0(P＞0.05);serum MDA level in the observation group was significantly lower than that in the control group(P＜0.05).At T3 and T5,serum SOD level in the control group was significantly lower than that at T0,while serum SOD level in the observation group was significantly higher than that at T0(P＜0.05);serum SOD level in the observation group was significantly higher than that in the control group(P＜0.05).Four patients in the observation group experienced symptoms of unilateral recurrent laryngeal nerve block,and one patient experienced brachial plexus nerve block,but all improved within 24 hours after surgery.No other adverse reactions were observed during follow-up.Within 72 hours postoperatively,one patient in the control group experienced hypoxemia.Conclusion Preoperative ultrasound-guided SGB has lung-protective effects on patients undergoing OLV in thoracoscopic surgery,which significantly improves OI,reduces intrapulmonary shunts,and inhibits inflammatory response and oxidative stress.
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Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.
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ObjectiveTo determine the influence of COVID-19 prevention and control on the epidemic characteristics and dynamics of notifiable infectious diseases in the first quarters， Zhejiang Province， and to explore more effective countermeasures against infectious diseases. MethodsDescriptive epidemiology was conducted to determine the change in notifiable infectious diseases during the prevention and control of COVID-19 in Zhejiang Province by retrieving the data of notifiable infectious diseases from 2017 to 2022 in the Chinese information system for disease control and prevention. Cumulative reported new cases of notifiable infectious diseases in the first quarters of 2017‒2019 were compared with that of 2020‒2022. ResultsA total of 546 753 cases of notifiable infectious diseases were newly reported in the first quarters of 2017‒2019， with an average incidence of 321.92/105. In contrast， a total of 509 908 cases of notifiable infectious diseases were newly reported in the first quarters of 2020‒2022， during which the COVID-19 epidemic occurred， with an average incidence of 270.39/105. The incidence in 2020‒2022 significantly declined by 51.53/105， compared with that in 2017‒2019 （χ²=8 072.06， P<0.001）. In the first quarters of 2020‒2022， the average incidence of zoonotic diseases and vector-borne diseases decreased by more than 50%. In addition， the incidence of respiratory， enteric， blood-borne， and sexually transmitted diseases declined to certain degree. ConclusionThe decline in the newly reported cases of non-COVID-19 notifiable infectious diseases in the first quarters of 2020‒2022 indicates that the countermeasures against COVID-19 epidemic， such as multi-disease co-prevention， multi-sectoral collaboration， societal mobilization and personal hygiene and protection， may also decrease the incidence of multiple infectious diseases. It suggests the countermeasures are effective， which would provide evidence for routine prevention and control of infectious diseases in future.
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AIM:To investigate the changes in the macular microvasculature in eyes with central retinal artery occlusion(CRAO)and paracentral acute middle maculopathy(PAMM).METHODS: Retrospective study. A total of 27 cases(27 eyes)who diagnosed with CRAO-PAMM and 29 patients(29 eyes)diagnosed as CRAO but with no PAMM were hospitalized in our hospital from January 2020 to December 2021. There were 33 normal people(33 eyes)who underwent physical examination in our hospital selected as control group. Optical coherence tomography angiography(OCTA)was used to measure retinal blood flow and thickness parameters in the 3 mm×3 mm area of the macula. The correlation among macular retinal blood flow density, retinal thickness, foveal avascular zone(FAZ)area, FAZ perimeter, acircularity index(AI), flow density in a 300-μm-wide region around the FAZ(FD-300)and lesion area, best corrected visual acuity(BCVA)in the CRAO-PAMM group was analyzed.RESULTS: Among the three groups, there were significant differences in the overall and parafoveal blood flow density of superficial capillary layer(SCP)and deep capillary layer(DCP), foveal thickness, FAZ area, FAZ perimeter, AI and FD-300(all P<0.05). In the CRAO-PAMM group, the lesion area was negatively correlated with DCP overall and parafoveal blood flow density(r=-0.569, P=0.002; r=-0.543, P=0.004), and positively correlated with the parafoveal thickness(r=0.606, P=0.001); BCVA(LogMAR)was negatively correlated with DCP foveal and parafoveal blood flow density(r=-0.433, P=0.024; r=-0.515, P=0.006), and positively correlated with FAZ area, perimeter and lesion area(r=0.484, P=0.011; r=0.531, P=0.004; r=0.417, P=0.030).CONCLUSION:Patients with CRAO and PAMM have lower macular blood flow density, heavier macular edema and poorer visual acuity, and BCVA may be influenced by both lesion area and FAZ area.
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With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.
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Humanos , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Biliar , Cálculos Biliares , Laparoscopía , Resultado del Tratamiento , Envejecimiento , Estudios RetrospectivosRESUMEN
OBJECTIVE@#To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities.@*METHODS@#A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay.@*RESULTS@#WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3).@*CONCLUSION@#The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
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Niño , Femenino , Humanos , Masculino , Embarazo , Exones , Discapacidad Intelectual/genética , Madres , Mutación , Quinasas p21 Activadas/genética , Padres , Empalme del ARNRESUMEN
OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1).@*METHODS@#A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected.@*RESULTS@#After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05).@*CONCLUSIONS@#Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
Asunto(s)
Animales , Femenino , Masculino , Conejos , Electroacupuntura , Músculo Esquelético , Atrofia Muscular/terapia , FN-kappa B/genética , Traumatismos de los Nervios Periféricos , Ratas Sprague-Dawley , Nervio CiáticoRESUMEN
It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.
Asunto(s)
Ratas , Animales , Ratas Endogámicas SHR , Núcleo Hipotalámico Paraventricular/fisiología , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Ratas Endogámicas WKY , Hormona Liberadora de Corticotropina/metabolismo , Neuronas/fisiología , Hipertensión , Sistema Nervioso SimpáticoRESUMEN
This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.