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With the increasing incidence of diabetes mellitus in recent years， cardiomyopathy caused by diabetes mellitus has aroused wide concern and this disease is characterized by high insidiousness and high mortality. The early pathological changes of diabetic cardiomyopathy （DCM） are mitochondrial structural disorders and loss of myocardial metabolic flexibility. The turbulence of mitochondrial quality control （MQC） is a key mechanism leading to the accumulation of damaged mitochondria and loss of myocardial metabolic flexibility， which， together with elevated levels of oxidative stress and inflammation， trigger changes in myocardial structure and function. Qi deficiency and stagnation is caused by the loss of healthy Qi， and the dysfunction of Qi transformation results in the accumulation of pathogenic Qi， which further triggers injuries. According to the theory of traditional Chinese medicine （TCM）， DCM is rooted in Qi deficiency of the heart， spleen， and kidney. The dysfunction of Qi transformation leads to the generation and lingering of turbidity， stasis， and toxin in the nutrient-blood and vessels， ultimately damaging the heart. Therefore， Qi deficiency and stagnation is the basic pathologic mechanism of DCM. Mitochondria， similar to Qi in substance and function， are one of the microscopic manifestations of Qi. The role of MQC is consistent with the defense function of Qi. In the case of MQC turbulence， mitochondrial structure and function are impaired. As a result， Qi deficiency gradually emerges and triggers pathological changes， which make it difficult to remove the stagnant pathogenic factor and aggravates the MQC turbulence. Ultimately， DCM occurs. Targeting MQC to treat DCM has become the focus of current research， and TCM has the advantages of acting on multiple targets and pathways. According to the pathogenesis of Qi deficiency and stagnation in DCM and the modern medical understanding of MQC， the treatment should follow the principles of invigorating healthy Qi， tonifying deficiency， and regulating Qi movement. This paper aims to provide ideas for formulating prescriptions and clinical references for the TCM treatment of DCM by targeting MQC.
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Objective:To explore the correlation between c-myc and glutaminase(GLS)and glutamine synthase(GS)in oral epider-moid carcinoma cells in animal models.Methods:Immunohistochemistry was used to detect the expression of c-myc,GLS and GS in clinical samples of oral cancer.KB cell model with stable and high expression of c-myc was established and verified,then the KB cells were transplanted into nude mice to establish mouse tumorigenic models.The cells and nude mouse models were respectively diveded into 3 groups(n=6):normal cotnrol,empty vector and c-myc overexpression groups.The tumor growth was observed.The expression of c-myc,GLS and GS in the cells and the tumor samples was detected by immunohistochemistry.Results:c-myc,GLS and GS were highly expressed in clinical samples of oral cancer.In the cells of c-myc overexpression group c-myc mRNA expression level was sig-nificantly higher than that of empty vector control group.The tumorigenic models were formed in all nude mice of the groups,and the volume and weight of the c-myc overexpression group increased more significantly(P＜0.01),in the c-myc overexpression group c-myc was overexpressed,the expression of GLS and GS was significantly higher than that in the other 2 groups.Conclusion:c-myc is highly expressed in oral cancer,and may up-regulate GLS and GS expression.
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Objective To explore the effect of individualized positive end expiratory pressure guided by driving pressure on lung protection after laparoscopic radical gastrectomy for elderly patients.Methods A total of 64 patients underwent elective laparoscopic radical gastrectomy for gastric cancer in the Second Affiliated Hospital of Anhui Medical University were selected.According to the random number table method,patients were divided into the driving the pressure guided individualized positive end-expiratory pressure(PEEP)group(experimental group)and the fixed PEEP group(control group),32 cases in each group.In the control group,PEEP = 5 cmH2O.In the experimental group,PEEP titration was performed according to the increasing method,and the PEEP corresponding to the lowest driving pressure was selected until extubation.Peak airway pressure(Ppeak),plateau airway pressure(Pplat)and PEEP were recorded at 5 min after intubation(T1),immediately after PEEP titration(T2),1 h after operation(T3),2 h after operation(T4),and 10 min after pneumoperitoneum release(T5).Driving pressure(ΔP)and lung dynamic compliance(Cdyn)were calculated.Arterial blood was collected at T1-5 for blood gas analysis,arterial partial pressure of oxygen(PaO2)was recorded,and oxygenation index(OI)was calculated.The occurrence of pulmonary complications(PPCs)within 7 days after operation was recorded.Modified clinical pulmonary infection score(mCPIS)was recorded on the second day after operation.The pulmonary function was evaluated before operation,1 day,3 days and 5 days after operation.Results Compared with T1,Ppeak,Pplat and ΔP were increased and Cdyn was decreased at T2-5,while OI was decreased at T4 in control group(P＜0.05).Compared with the control group,Ppeak,Pplat and Cdyn in the experimental group were increased at T2-5,ΔP was decreased,and OI was increased at T3-5(P＜0.05).Compared with the preoperative results,FVC at 1,3 and 5 days after surgery was decreased,and FEV1 and maximum expiratory flow(PEF)were decreased 1 and 3 days after surgery in the experimental groups(P＜0.05).Compared with the control group,FVC,FEV1 and PEF were higher 1 day after operation in the experimental group(P＜0.05).Compared with the preoperative results,mCPIS scores of the two groups were higher on the second day after surgery(P＜0.05).Compared with the control group,the mCPIS score was lower on day 2 after surgery in the experimental group(P＜0.05).The incidence of PPCs within 7 days after surgery was lower in the experimental group than that in the control group(15.6%vs.40.6%).Conclusion Individualized PEEP guided by drive pressure can improve lung compliance,reduce drive pressure,improve oxygenation function and early postoperative lung function,reduce the incidence of postoperative lung complications,and has a certain lung protection effect.
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Objective:To analyze the clinical symptoms and laboratory characteristics of patients with brucellosis combined with osteoarthritis.Methods:A retrospective analysis was conducted on the medical records of 168 patients with brucellosis who were hospitalized at the Jining Public Health Medical Center, Shandong Province from January 2021 to December 2022. Based on the imaging examination results, they were divided into combined osteoarthritis group and non combined osteoarthritis group. The demographic characteristics, clinical symptoms, and laboratory test results of the two groups of patients were compared and analyzed.Results:Among 168 patients with brucellosis, there were 83 patients with concurrent osteoarthritis, 85 patients without concurrent osteoarthritis, the males and females ratio was 2.73 ∶ 1.00 (123 ∶ 45), and the age was 56 (46, 64) years old. The median age of patients in combined osteoarthritis group was higher than that of patients in non combined osteoarthritis group (58 years vs 53 years, Z = - 2.89, P = 0.004). In clinical symptoms, the incidence of back pain, fatigue, and joint muscle pain in patients of combined osteoarthritis group was significantly higher than that in the non combined osteoarthritis group [75.9% (63/83) vs 56.5% (48/85), 30.1% (25/83) vs 15.3% (13/85), 47.0% (39/83) vs 17.6% (15/85), χ 2 = 7.07, 5.27, 16.58, P < 0.05]. In laboratory tests, the erythrocyte sedimentation rate (ESR) and hypersensitive C-reactive protein (hs-CRP) levels in patients of combined osteoarthritis group were higher than those in the non combined osteoarthritis group [27.0 (17.0, 34.0) mm/h vs 21.0 (10.5, 34.0) mm/h, 22.7 (14.3, 43.4) mg/L vs 17.9 (10.8, 34.2) mg/L, Z = - 2.51, - 2.00, P < 0.05]. Among patients with combined osteoarthritis, combined spondylitis accounted for the highest proportion (55.4%, 46/83), followed by peripheral arthritis (51.8%, 43/83). Conclusion:Osteoarthritis is a common complication of brucellosis, and patients of brucellosis with concurrent osteoarthritis have clinical features such as lower back pain, fatigue, and joint muscle pain, with significantly elevated of ESR and hs-CRP level.
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Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m2) vs. (60±15) mL/(min·1.73 m2), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.
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Objective:To explore any effect of following an individualized exercise program on the cardio-pulmonary health of elderly persons with stable chronic obstructive pulmonary disease (COPD).Methods:A total of 120 elderly COPD patients were randomly divided into an experimental group and a control group, each of 60. Both groups were given medication and routine rehabilitation treatment for 3 months, but the experimental group also followed an individualized exercise program based on the cardiopulmonary exercise test. Before and after the treatment, Borg scoring was used to assess the subjects′ degree of dyspnea. Forced expiratory volume (FEV 1), forced vital capacity (FVC), maximum oxygen uptake (VO 2max), anaerobic threshold (AT), heart rate (HR) and a heart index (CI) were also recorded. The 6-minute walk test (6 MWD) was administered to evaluate the rehabilitation effect. Results:There were no significant differences in the average Borg scores, cardiopulmonary function indexes or 6MWD distances between the two groups before treatment. After the treatment significant improvement was observed in all of the measurements in both groups, but at that point all of the experimental group′s averages were better than those of the control group.Conclusion:Individualized exercise based on the cardiopulmonary exercise test can alleviate the symptoms of dyspnea in elderly COPD patients, improve their cardiopulmonary functioning and exercise endurance and improve the rehabilitation effect.
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Objective @#To develop an endoscopic automatic detection system in early gastric cancer (EGC) based on a region-based convolutional neural network ( Mask R-CNN) ．@*Methods @# A total of 3 579 and 892 white light images (WLI) of EGC were obtained from the First Affiliated Hospital of Anhui Medical University for training and testing，respectively．Then，10 WLI videos were obtained prospectively to test dynamic performance of the RCNN system．In addition，400 WLI images were randomly selected for comparison with the Mask R-CNN system and endoscopists．Diagnostic ability was assessed by accuracy，sensitivity，specificity，positive predictive value ( PPV) ， and negative predictive value (NPV) . @*Results @# The accuracy，sensitivity and specificity of the Mask R-CNN system in diagnosing EGC in WLI images were 90. 25% ，91. 06% and 89. 01% ，respectively，and there was no significant statistical difference with the results of pathological diagnosis．Among WLI real-time videos，the diagnostic accuracy was 90. 27%．The speed of test videos was up to 35 frames / s in real time．In the controlled experiment， the sensitivity of Maks R-CNN system was higher than that of the experts (93. 00% vs 80. 20% ，χ2 = 7. 059，P < 0. 001) ，and the specificity was higher than that of the juniors (82. 67% vs 71. 87% ，χ2 = 9. 955，P＜0. 001) ， and the overall accuracy rate was higher than that of the seniors (85. 25% vs 78. 00% ，χ2 = 7. 009，P＜0. 001) . @*Conclusion@#The Mask R-CNN system has excellent performance for detection of EGC under WLI，which has great potential for practical clinical application.
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Purpose To investigate the clinicopathological characteristics and prognostic correlation of the WHO(2021)new grading system of invasive pulmonary adenocarcinoma in stageⅠ pulmonary adenocarcinoma.Methods The clinical data of 447 patients with stage Ⅰ pulmonary adenocarcinoma were collect-ed,and all cases were evaluated according to the new grading system for invasive pulmonary adenocarcinoma.The immunohis-tochemical EnVision two-step method and elastic fiber staining were used to analyze the clinicopathological features with review of the relevant literature.Results In 447 patients with stage Ⅰlung adenocarcinoma,Napsin A and TTF-1 expression were posi-tive,p40 expression was negative,and Ki-67 proliferation index was higher than 5％in 177 patients(39.6％).There were 39 cases(8.7％)of positive pleural invasion in the visceral layer revealed by elastic fiber staining.The pleural invasion in stage Ⅰpulmonary adenocarcinoma patients was significantly higher than that in grades 2 and 3,the difference was statistically significant(P＜0.05).Patients with different grades of stage Ⅰ pulmonary adenocarcinoma were associated with gender,smoking history,surgical mode,chemotherapy,targeted medication,clinical stage,pathological classification,degree of differentiation,tumor size,vascular invasion,visceral pleural invasion,spread through air space(STAS)and Ki-67 index(P＜0.05).Survival analy-sis showed that there were statistically significant differences in disease free survival(DFS)and overall survival(OS)among different grades(grade 1＞grade 2＞grade 3)(P＜0.05).Cox regression analysis showed that WHO(2021)new grading of invasive pulmonary adenocarcinoma,visceral pleural invasion and Ki-67 proliferation index were independent risk factors for prognosis of patients with stage Ⅰ pulmonary adenocarcinoma.Conclusion The WHO(2021)new grading system of invasive pulmonary adenocarcinoma has good prognostic significance for stage Ⅰ pulmonary adenocarcinoma,and appropriate intervention for high-risk patients.It can effectively assist its postoperative treatment and has application value.
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Objective:To investigate the molecular epidemiological characteristics of HIV-1 infection among men who have sex with men (MSM) in Jiaxing city, and provide methods and ideas for the prevention and control of HIV-1 infection.Methods:This study retrospectively collected the blood samples from all newly reported cases of HIV-1 infection among MSM without antiviral treatment from 2020 to 2022. HIV-1 pol genes in the blood samples were amplified and sequenced. MEGA v6.0 software was used to analyze nucleic acid sequences. A phylogenetic tree was constructed to analyze HIV-1 subtypes. The calibrated population resistance program (CPR) was used to detect drug-resistant mutations. After calculating the genetic distance between gene sequences, molecular transmission networks were constructed using Cytoscape v3.6.0 software. Results:A total of nine genetic subtypes were identified, with CRF07_BC (43.3%) and CRF01_AE (36.9%) accounting for the most. The recombinant forms that were not clustered with the reference subtype accounted for 5.0%. Drug-resistant mutations were identified in 21 cases (7.0%), and the mutation rates among strains of CRF07_BC and CRF01_AE subtypes were 8.2% and 7.8%, respectively. The detection rates of drug-resistant mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors were 1.7%, 0.7% and 4.7%, respectively. The optimal genetic distance threshold of the molecular network was 0.018. At this genetic distance, the molecular network access rate was 43.3%, and 38 molecular clusters (ranging from 2 to 26 nodes per cluster) were included. Cases with ≥6 homosexual partners and a degree value of ≥4 were more likely to access the active molecular cluster. The population of high-risk transmission cases with TNS>0.75 were mainly nonlocal residents and commercial service providers. The recombinant forms showed high similarity in sequences with the strains from other provinces.Conclusions:The distribution of HIV-1 subtypes in MSM in Jiaxing city was complex. Given the increasing detection rate of recombinant forms, the high transmission rate of drug-resistant mutations, and the active molecular clusters and high-risk transmission clusters mainly detected in nonlocal residents and commercial service providers, strengthened surveillance and intervention are needed.
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Objective:To evaluate balloon compression-assisted endoscopic injection sclerotherapy (bc-EIS) for the treatment of esophageal varices.Methods:From June 2019 to November 2020, cirrhotic patients with esophageal varices who received endoscopic injection sclerotherapy (EIS) in the First Affiliated Hospital of Anhui Medical University were enrolled in the study. The patients were randomly divided into the bc-EIS group and the traditional EIS group. The number of treatments to eradicate varicose veins, the dose of sclerosing agent used in the first treatment, the number of injection points in the first treatment, the rebleeding rate within 10 months after the operation and the incidence of complications or adverse reactions were compared between the two groups.Results:Ninety-two cases were initially included in the study, and 7 cases were excluded based on exclusion criteria. Finally, 85 cases were included in the data analysis, 47 in the bc-EIS group and 38 in the traditional EIS group. The first eradication rate, the second cumulative eradication rate and the third cumulative eradication rate were 82.98% (39/47), 91.49% (43/47) and 100.00% (47/47) in the bc-EIS group, and they were 10.53% (4/38) ( χ 2=44.125, P<0.001), 31.58% (12/38) ( χ 2=33.023, P<0.001) and 63.16% (24/38) ( χ 2=20.730, P<0.001), respectively in the traditional EIS group, and the differences were statistically significant. The treatment times of eradicating varicose veins in the bc-EIS group and the traditional EIS group were 1.25±0.60 and 3.21±1.41, respectively, with significant difference. The dosage of sclerosing agent in first treatment in the bc-EIS group and the traditional EIS group was 17.66±7.14 mL and 22.92±6.84 mL, respectively ( t=3.441, P=0.001). The numbers of initial injection points in the bc-EIS group and the traditional EIS group were 2.70±0.86 and 2.78±1.04, respectively and the difference was not statistically significant ( t=1.847, P=0.065). The rebleeding rates of the two groups within 10 months after the operation were 2.13% (1/47) and 18.42% (7/38) respectively ( χ 2=4.771, P=0.029). There were no serious complications in the two groups. The incidences of retrosternal pain, nausea and vomiting, abdominal distension and ulcer were 2.13% (1/47), 2.13% (1/47), 4.26% (2/47) and 0.00% (0/47) in the bc-EIS group, and in the traditional EIS group, they were 5.26% (2/38) ( χ 2=0.035, P=0.851), 5.26% (2/38) ( χ 2=0.035, P=0.851), 7.89% (3/38) ( χ 2=0.060, P=0.806) and 7.89% (3/38) ( χ 2=1.877, P=0.171), respectively, without significant difference. Conclusion:Bc-EIS is more effective than traditional EIS for the treatment of esophageal varices with lower postoperative rebleeding rate, which shows better clinical application value.
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Objective To prepare specific mouse monoclonal antibody (mAb) against human adenovirus type 55 Hexon protein (HAdV55 Hexon). Methods The Hexon genes of HAdV55, 3, 4, 7, 16 and 21 were chemically synthesized as templates for PCR amplification. The prokaryotic expression plasmids pET28a-HAdV55 Hexon and eukaryotic expression plasmids pCAGGS-HAdV3, 4, 7, 16, 21 and 55 Hexon were constructed respectively. The pET28a-HAdV55 Hexon plasmid was transformed into E. coli competent cell BL21 (DE3) and was induced by IPTG. After the purified inclusion body was denatured and renatured, Hexon55 protein was purified by tangential flow filtration system. pCAGGS-HAdV55 Hexon was used to immunize BALB/c mice by cupping, and HAdV55 Hexon protein was used to booster immunization. The anti-HAdV55 Hexon mAb was prepared by hybridoma technique and the titer and subclass were determined. The specificity of antibody was identified by Western blot using HEK293T cells transfected with pCAGGS-HAdV55 Hexon and by immunofluorescence assay (IFA) using BHK cells transfected with pCAGGS-HAdV55 Hexon. Both clones with high titer were selected, and the cross-reactivity of pCAGGS-HAdV3, 4, 7, 16, 21 and 55 Hexon transfected cells were analyzed by Western blot analysis and IFA. Results PET28a-HAdV55 Hexon and pCAGGS-HAdV55 Hexon, 3, 4, 7, 16 and 21 expression plasmids were successfully constructed. BL21 transformed with pET28a-HAdV55 Hexon was induced by IPTG. The HAdV55 Hexon protein was mainly expressed in the form of inclusion body. After denaturation and renaturation, the purified HAdV55 Hexon protein was obtained by ultrafiltration. Six hybridoma cell lines secreting HAdV55 Hexon mAb were obtained. The antibody subclass analysis showed that 2 strains were IgG2a subtypes and 4 strains were IgG2b. Two specific HAdV55 Hexon antibodies with high titer were obtained, and there was no cross-reactivity with HAdV3, 4, 7, 16, 21 Hexon. Conclusion The specific mice mAb against HAdV55 Hexon provides an experimental basis for establishing its antigen detection method.
Asunto(s)
Animales , Ratones , Humanos , Adenovirus Humanos/genética , Escherichia coli/genética , Células HEK293 , Isopropil Tiogalactósido , Western Blotting , Inmunoglobulina G , Anticuerpos Monoclonales , Especificidad de Anticuerpos , Ratones Endogámicos BALB CRESUMEN
Objective:To investigate the disease spectrum referred from the community health service centers to the district tertiary hospital in the region.Method:The data of the referred patients from the community health service centers to Shanghai Yangpu District Hospital-a tertiary hospital in the region from January 2016 to December 2019 were collected. The composition and characteristics of the disease spectrum of the referred patients were analyzed.Results:The number of patient visits to the community health service centers in the region was increased from 4 684 938 in 2016 to 4 776 921 in 2019. The number of patient referral from the community centers to Yangpu Hospital was increased from 3 125 in 2016 to 6 853 in 2019. There were total 18 308 patients referred in 4 years, including 8 012 males (43.8%) and 10 296 females (56.2%). The age range of referred patients was from 1 to 99 years, including 53 referred patients aged ≤ 18 (0.3%), 927 aged 19-39 (5.1%), 2 831 aged 40-59 (15.5%), 4 424 aged 60-79 (62.2%) and 1 209 aged ≥ 80 (17%). The top five systems of diseases, which accounted more than 60% of total diseases, were circulatory system, endocrine nutrition and metabolic system, urogenital system, eye and appendage, and digestive system. Compared with male patients, more female patients with urogenital diseases were referred.Conclusion:The referral rate of community health service centers were increased from 2016 to 2019. The referred patients cover all age groups, more frequently in age group 60-79. The diseases of referred patients cover all system, and are different between males and females.
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Objective:To analyze the current situation of public health management and public health services in public hospitals at the second level and above in Anhui Province, for references for the government to formulate relevant policies.Methods:A stratified whole-group random sampling method was used to investigate the current status of public health services provided by 55 public hospitals at the second level and above in Anhui Province. The contents of the questionnaire included the establishment of public health management departments, operation and public health services. Descriptive analysis was conducted for all data, and chi-square test was used for comparison between groups.Results:Of the 55 hospitals, only one tertiary hospital had a separate public health department, while the public health management works of the other hospitals were scattered among the hospital infection department, medical affairs department, preventive health department and so on. 32 hospitals putted the public health services into their performance appraisal. Among the public health services provided by hospitals, the management of infectious disease diagnosis and treatment presented the best performance, as 55 hospitals had established relevant management systems, processes, business training, infectious disease reporting and other information systems. Mental health service presented the poorest performance, as only 36 hospitals had established relevant management systems.Conclusions:The public health management and service level of public hospitals in Anhui Province needed to be further improved. The government authorities should strengthen their top-level design and coordinate the public health department setup and performance evaluation mechanism of public hospitals from the institutional level. On the other hand, the public hospitals should constantly optimize their content of public health services, complement the weaknesses, and effectively improve the level of public health services based on respective conditions of the hospitals.
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Objective To investigate the predictive and diagnostic value of absolute value and function of different lymphocyte subsets in evaluating the risk of early viral infection after kidney transplantation. Methods Ninety-five kidney transplant recipients were enrolled in this prospective observational cohort study, and divided into the stable group (n=77) and infection group (n=18) according to postoperative immune status. Peripheral blood samples were collected for flow cytometry before operation, and 2 weeks, 1 month, 2 months and 6 months after operation. The dynamic changes of the absolute values of CD4+T cells, CD8+T cells and natural killer (NK) cells were compared between two groups. The function of lymphocyte subsets in two groups was evaluated by detecting the proportion of interferon (IFN)-γ+CD4+T cells, IFN-γ+CD8+T cells and IFN-γ+NK cells. The value of the absolute values and function of lymphocyte subsets in predicting and diagnosing viral infection in the early stage after kidney transplantation was evaluated. Results During viral infection, the absolute values of CD4+T cells, CD8+T cells and NK cells in the infection group were at a relatively low level. At 2 months after operation, the absolute values of CD4+T cells and NK cells in the infection group were lower than those in the stable group. At 6 months after operation, the absolute values of CD4+T cells and CD8+T cells in the infection group were significantly lower compared with those in the stable group (all P < 0.05). During viral infection, the proportion of IFN-γ+CD4+T cells, IFN-γ+CD8+T cells and IFN-γ+NK cells in the infection group were all at a relatively low level, especially that of IFN-γ+CD8+T cells decreased most significantly. At postoperative 2 months, the proportion of IFN-γ+CD8+T cells and IFN-γ+NK cells in the infection group was significantly higher than those in the stable group. At 6 months after operation, the proportion of IFN-γ+CD4+T cells and IFN-γ+CD8+T cells in the infection group was significantly higher than those in the stable group (all P < 0.05). Logistic regression analysis showed that the increasing proportion of IFN-γ+CD8+T cells and IFN-γ+NK cells was correlated with the increasing risk of viral infection at 2 months after operation (both P < 0.05). The receiver operating characteristic (ROC) curve demonstrated that the diagnostic value of absolute values of lymphocyte subsets combined with IFN-γ secretion function for viral infection in the immunocompromised recipients was significantly higher than that of absolute values of lymphocyte subsets alone (P < 0.05). Conclusions Dynamic monitoring of the changes of absolute values and function of lymphocyte subsets provides critical reference value for the prediction, diagnosis and medication guidance of viral infection.
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ObjectiveTo explore the influence of structure and process variables on the satisfaction of government purchasing pension service quality based on framework of Donabedian Three-Dimensional Quality Model, Community-based Rehabilitation Guideline and Rehabilitation in Health System. MethodsFrom June to December, 2019, 952 elderly from Changsha, Zhuzhou and Xiangtan in Hunan were randomly selected. Hierarchical regression was used to analyze the influence of structure and process variables on satisfaction of home care and institutional care service quality. ResultsThe satisfaction degree of rehabilitation service quality for older adults was generally abvoe the average level with the score of (21.19±6.84). And the score was higher in the institutional rehabilitation (23.06±7.67) than in the home rehabilitation (19.31±6.85) (t = 7.93, P = 0.001). Among the structural variables, only staffs training could predict the satisfaction of rehabilitation service (B = 0.088, P < 0.05), and finance was not significant (P > 0.05) after adding process variables. The effect of process variables on satisfaction degree of quality of rehabilitation services was greater than that of structural variables. Information obtaining, autonomy, trust and treat with respect had significant positive effects on rehabilitation service of all the elderly (B = 0.282~0.410, P < 0.05). ConclusionProcess variables are important determinants for satisfaction of rehabilitation service quality. Relevant departments should pay more attention on service process factors such as the interaction between service personnel and the elderly.
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Objective:To investigate the clinical efficacy and safety of balloon compression-assisted endoscopic injection sclerotherapy (bc-EIS) for esophageal varices in patients with cirrhosis.Methods:From December 2020 to April 2021, cirrhotic patients with esophageal varices who planned to receive endoscopic treatment in the Department of Gastroenterology of the First Affiliated Hospital of Anhui Medical University were selected and randomly divided into the trial group (treated with bc-EIS) and the control group [treated with endoscopic variceal ligation (EVL)] through computer randomization. The varices eradication rate, rebleeding rate and postoperative adverse reactions in the two groups were studied.Results:During the study, 93 cases were initially included according to inclusion criteria, among which 9 cases were excluded by exclusion criteria. Finally, 84 cases were included for data analysis, with 42 cases in each group. The esophageal varices eradication rate after the first treatment in the trial group was 88.10% (37/42), which was significantly higher than that in the control group [33.33% (14/42)] ( χ2=26.40, P<0.001). The esophageal varices eradication rate after 1 to 2 times and 1 to 3 times of treatment in the trial group were both significantly higher than those in the control group [97.62% (41/42) VS 40.48% (17/42), χ2=29.47, P<0.001; 100.00% (42/42) VS 45.24% (19/42), P<0.001]. The maximum follow-up period was 6 months, and none of the patients had rebleeding in the trial group, and the rebleeding rate in the control group was 4.76% (2/42) ( P=0.494). The incidence of thoracic and abdominal discomfort, nausea and vomiting, and abdominal distension in the trial group and control group were 26.19% (11/42) and 35.71% (15/42) ( χ2=0.51, P=0.474), 2.38% (1/42) and 7.14% (3/42) ( χ2=0.26, P=0.608), and 4.76% (2/42) and 11.90% (5/42) ( χ2=0.62, P=0.430), respectively. No other adverse events such as infection, dysphagia, perforation, esophageal tracheal fistula, esophageal stenosis, or ectopic embolism occurred in any group. Conclusion:Bc-EIS is effective and safe for the treatment of esophageal varices in patients with cirrhosis, with a one-time varices eradication rate of more than 85%, and can be completely eradicated after 1 to 3 times of treatment.
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Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines. One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.
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The newly emerging variants of SARS-CoV-2 from India (Delta variant) and South America (Lambda variant) have led to a higher infection rate of either vaccinated or unvaccinated people. We found that sera from Pfizer-BioNTech vaccine remain high reactivity toward the receptor binding domain (RBD) of Delta variant while it drops dramatically toward that of Lambda variant. Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which could be one of major reasons for breakthrough infections, emphasizing the importance of potential third boost shot. While a therapeutic antibody, Bamlanivimab, decreases binding affinity to Delta variant by ~20 fold, it fully lost binding to Lambda variant. Structural modeling of complexes of RBD with human receptor, Angiotensin Converting Enzyme 2 (ACE2), and Bamlanivimab suggest the potential basis of the change of binding. The data suggest possible danger and a potential surge of Lambda variant in near future.
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We generated several versions of the receptor binding domain (RBD) of the Spike protein with mutations existing within newly emerging variants from South Africa and Brazil. We found that the mutant RBD with K417N, E484K, and N501Y exchanges has higher binding affinity to the human receptor compared to the wildtype RBD. This mutated version of RBD also completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro.
RESUMEN
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing a world-wide pandemic. A variant of SARS-COV-2 (20I/501Y.V1) recently discovered in the United Kingdom has a single mutation from N501 to Y501 within the receptor binding domain (Y501-RBD), of the Spike protein of the virus. This variant is much more contagious than the original version (N501-RBD). We found that this mutated version of RBD binds to human Angiotensin Converting Enzyme 2 (ACE2) a ~10 times more tightly than the native version (N501-RBD). Modeling analysis showed that the N501Y mutation would allow a potential aromatic ring-ring interaction and an additional hydrogen bond between the RBD and ACE2. However, sera from individuals immunized with the Pfizer-BioNTech vaccine still efficiently block the binding of Y501-RBD to ACE2 though with a slight compromised manner by comparison with their ability to inhibit binding to ACE2 of N501-RBD. This may raise the concern whether therapeutic anti-RBD antibodies used to treat COVID-19 patients are still efficacious. Nevertheless, a therapeutic antibody, Bamlanivimab, still binds to the Y501-RBD as efficiently as its binds to N501-RBD.
