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ObjectiveTo identify the rate， population characteristics， and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai， and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics， nucleic acid or antigen test results， and symptoms after infection. The repeat infection rates among different populations were compared， and logistic regression was used to analyze the impact of gender， age， and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males （53.40%） and 3 528 females （46.60%）， with a median age of 34 years old （P25， P75： 7， 61）. The overall vaccine uptake rate was 59.44% （4 500/7 571）. In December of 2022， there were 563 cases of repeat infection， with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group （2.86%） and the highest rate in the 30‒ year-old group （12.42%）， with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower （6.57%） compared to those who had not （7.11%）. The age groups of 3‒ years， 70‒79 years， as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant， and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots， it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.
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Objective To understand the epidemiological characteristics of new occupational pneumoconiosis in Zigong City from 2018 to 2022, and to provide the basis for further prevention and treatment of local pneumoconiosis. Methods The information of newly diagnosed and reported cases of pneumoconiosis in Zigong City from 2018 to 2022 was collected through the occupational disease and occupational health information monitoring system, and the characteristics of the distribution of pneumoconiosis in three regions, the composition of diseases and the length of service of exposure to dust were analyzed. Results From 2018 to 2022, the top 3 newly diagnosed pneumoconiosis diseases in Zigong City were silicosis, coal workers' pneumoconiosis and asbestosis. Silicosis cases were mainly distributed in small and medium-sized employers, accounting for 81.41%. Coal workers' pneumoconiosis was mainly distributed in large and medium-sized employers, accounting for 97.24%. Asbestosis mainly distributed in large scale employers, accounting for 96.36%. There was significant difference in dust handling age of different scale employers (H=11.453, P<0.05). The median ages of silicosis, coal workers' pneumoconiosis and other pneumoconiosis were 47.0 years, 52.0 years and 48.2 years, respectively. The median age of dust handling was 3.3 years, 22.0 years and 23.2 years, respectively. The age of onset of coal workers' pneumoconiosis was higher than that of silicosis and other pneumoconiosis (H=72.547, P<0.05), and the age of dust exposure of silicosis was shorter than that of coal workers' pneumoconiosis and other pneumoconiosis (H=10.453, P<0.05). Conclusion The current situation of pneumoconiosis in Zigong City is still severe, with obvious clustering in disease types and industries. Prevention and treatment of pneumoconiosis in key industries should be further strengthened to protect the health rights and interests of workers.
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Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.
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Alternative splicing is the key to human gene expression regulation and plays a decisive role in enlarging the diversity of functional proteins. Alternative splicing is an important biomarker in tumor progression, which is closely related to the development of tumors. Tumor cells tend to produce alternative spliceosome that are conducive to their progression. Therefore, targeting regulation of tumor-specific alternative spliceosomes is a potential strategy for tumor therapy. Herein, we provide a brief review of the complex relationship between alternative splicing and tumors. Alternative splicing works by removing non-coding sequences of pre-mRNA and assembling protein-coding fragments in different combinations, ultimately producing proteins with different or even opposite functions. Alternative splicing events can promote the transformation of tumor cells through apoptosis, invasion, metastasis, angiogenesis, and metabolism; they can also influence the effectiveness of cancer immunotherapy by affecting genes that play a key role in the immune pathway. We proposed that direct or indirect targeting of alternative splicing factors and oligonucleotide-based therapies are the main strategies to reverse tumor alternative splicing events. These findings will help us to better understand tumor-related alternative splicing and to develop new strategies for tumor treatment.
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Autophagy is an important physiological process that can degrade cell components and maintain cell homeostasis, divided into three types including macroautophagy, microautophagy and chaperon-mediated autophagy generally, and macroautophagy is the most common form. Autophagy can affect the progression of a variety of diseases, such as cancer, neurodegenerative diseases, heart-related diseases, and autoimmune diseases, etc. However, autophagy can promote or inhibit diseases in different circumstances because of the dual roles of autophagy. Therefore, targeted regulating autophagy may be a potential treatment plan for diseases in specific stages of disease development. Now, with the development of traditional Chinese medicine (TCM) resources and the deepening of researches on the modern utilization of TCM, many active compounds from TCM have been discovered that can target autophagy to exert pharmacological activity. Most of the natural compounds activate or inhibit autophagy by affecting the classical PI3K/AKT/mTOR autophagy pathway. In addition, some compounds can also affect autophagy through MAPKs signaling pathways such as MEK/ERK, JNK and p38MAPK. These active compounds exert various biological activities by regulating autophagy, including anti-tumor, inhibiting neurodegenerative diseases, protecting cardiomyocytes, and relief of inflammatory response. In this review, we summarized the active compounds in TCM that affect autophagy by targeting different signaling pathways and their mechanisms of regulating autophagy, also introduced the effects of active compounds on diseases after affecting autophagy. Finally, this paper summarized and prospected the development of targeted autophagy for the treatment of diseases by TCM compounds, hoping to provide clues for subsequent exploration and research.
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BackgroundDepression is a kind of disease with relatively high suicide risk， which seriously affects the quality of life of patients and their families， and brings a great burden to society. Antidepressants in western medicine are effective， but the improvement of depressive symptoms is relatively limited by single use， and the combination of two antidepressants may increase the risk of adverse reactions in patients. The rational use of Chinese patent medicine and western medicine may play a complementary role， and the safety of Chinese patent medicine is high. ObjectiveTo explore the early clinical efficacy of fluoxetine combined with Shugan Jieyu capsule in the treatment of depression， and to compare the differences in efficacy， safety and influence on heart rate variability between fluoxetine combined with Shugan Jieyu capsule and fluoxetine alone， so as to provide references for clinical medication of depression patients. MethodsFrom December 2015 to June 2016， 64 patients who met the diagnostic criteria of depression in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） who were hospitalized in the Second Affiliated Hospital of Xinxiang Medical University were selected as the research objects， and were randomly divided into the combined medication group and the fluoxetine group with 32 patients in each group. Patients in both groups were treated with fluoxetine， while patients in the combined medication group were treated with Shugan Jieyu capsule on this basis. Patients in both groups were assessed with Hamilton Depression Scale-24 item （HAMD-24）， Hamilton Anxiety Scale （HAMA） and Heart Rate Variability （HRV） before treatment， and were assessed with HAMD-24 and Treatment Emergent Symptom Scale （TESS） at the end of the 2nd， 4th and 6th week of treatment， and HRV was analyzed again at the end of the 6th week of treatment. ResultsThe study ultimately included 60 patients with depression， with 30 cases in the combination therapy group and 30 cases in the fluoxetine group. At the end of the 2nd， 4th and 6th week of treatment， the HAMD-24 score of the combined drug group was lower than that of the fluoxetine group （t=-2.677， -3.960， -4.432， P<0.05 or 0.01）. Compared with before treatment， the 24-hour mean standard deviation of normal RR intervals （SDNN）， normal low frequency （nLF） and normal high frequency （nHF） in the combined treatment group were higher at the end of the 6th week （t=-73.970， -31.878， -38.721， P<0.01）， but significant lower in LF/HF （t=3.525， P<0.01）. At the end of the 6th week of treatment， the total effective rate of the combined treatment group was higher than that of fluoxetine group， and the difference was statistically significant （86.67% vs. 70.00%， χ2=18.764， P<0.01）. At the 2nd， 4th and 6th week of treatment， there was no significant difference in the number of adverse reactions between the two groups （P>0.05）. ConclusionCompared with fluoxetine alone， Shugan Jieyu capsule combined with fluoxetine may be better in clinical efficacy and improvement of heart rate variability in patients with depression， without increasing adverse reactions.
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@# Objective To analyze the risk factors for postoperative length of stay (PLOS) after mediastinal tumor resection by robot-assisted non-endotracheal intubation and to optimize the perioperative process. Methods The clinical data of patients who underwent Da Vinci robot-assisted mediastinal tumor resection with non-endotracheal intubation at the Department of Thoracic Surgery, General Hospital of Northern Theater Command from 2016 to 2019 were retrospectively analyzed. According to the median PLOS, the patients were divided into two groups. The univariate analysis and multivariate logistic regression were used to analyze risk factors for prolonged PLOS (longer than median PLOS). Results A total of 190 patients were enrolled, including 92 males and 98 females with a median age of 51.5 (41.0, 59.0) years. The median PLOS of all patients was 3.0 (2.0, 4.0) d. There were 71 patients in the PLOS>3 d group and 119 patients in the PLOS≤3 d group. Multivariate logistic regression showed that indwelled thoracic catheter [OR=11.852, 95%CI (2.384, 58.912), P=0.003], preoperative symptoms of muscle weakness [OR=4.814, 95%CI (1.337, 17.337), P=0.016] and postoperative visual analogue scale>5 points [OR=6.696, 95%CI (3.033, 14.783), P<0.001] were independent factors for prolonged PLOS. Totally no tube (TNT) allowed patients to be discharged on the first day after surgery. Conclusion Robot-assisted mediastinal tumor resection with non-endotracheal intubation can promote rapid recovery. The methods of optimizing perioperative process are TNT, controlling muscle weakness symptoms and postoperative pain relief.
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@#Objective To compare the clinical efficacy and safety of da Vinci robot with totally no tube (TNT) versus subxiphoid video-assisted thymectomy surgery (SVATS) in the treatment of thymic tumors. Methods From 2019 to 2021, a retrospective analysis was conducted on patients with thymic tumor resection in the Department of Thoracic Surgery, General Hospital of Northern Theater Command. All patients underwent total thymectomy and mediastinal fat removal, and they were divided into a TNT group and a SVATS group according to the operation method. The intraoperative blood loss, conversion rate, postoperative visual analogue score (VAS), postoperative hospital stay time and postoperative complications were compared between the two groups. Results We finally included 435 patiets. There were 168 patients with 83 males and 85 females at an average age of 61.920±9.210 years in the TNT group and 267 patients with 147 males and 120 females at an average age of 61.460±8.119 years in the SVATS group. There was no death or postoperative myasthenic crisis in both groups. There was no statistical difference in postoperative hospital stay (1.540±0.500 d vs. 3.400±0.561 d, P=0.000), intraoperative blood loss (13.450±5.498 mL vs. 108.610±54.462 mL, P=0.000), postoperative 24 h VAS score (4.960±1.757 points vs. 3.600±1.708 points, P=0.000), or postoperative complication rate (3.0% vs. 11.6%, P=0.001). Conclusion TNT is a more efficient, safe, and effective surgical approach for treating thymic tumors, which can shorten hospital stay time and reduce postoperative complications. However, SVATS can minimize postoperative pain.
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Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.
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Objective:To purify H5N1 influenza virus concentrate prepared by MDCK cells with a new mixed-mode chromatography medium Capto Core700 and the traditional medium Sepharose 4FF, and to compare the separation and purification efficacy of the two media.Methods:Capto Core700 and Sepharose 4FF were used to purify inactivated H5N1 influenza virus concentrate. The morphology of virus particles in different samples was then observed under a transmission electron microscope. Single radial immunodiffusion (SRID), Folin-Phenol (Lowry) method, double-antibody sandwich ELISA and qPCR were used to detect hemagglutinin, total protein, host cell protein (HCP) and host cell DNA (HCD) before and after purification. The recovery rate of virus antigen and the removal rate of impurities were calculated. The immunogenicity of the viruses purified with different media was analyzed using animal experiments. Difference in the purification efficacy of the two chromatography media was analyzed by t-test. Results:H5N1 influenza viruses purified by Capto Core700 or Sepharose 4FF showed the typical influenza virus morphology under transmission electron microscope. There was no significant difference in the recovery rate of hemagglutinin between the two chromatography media ( P>0.05), but compared with Sepharose 4FF, Capto Core700 had a higher removal rate of impurities (total protein, HCP, HCD) and the difference was statistically significant ( P<0.05). Animal experiments showed that the viruses purified by the two chromatography media had good immunogenicity. Conclusions:Compared with Sepharose 4FF chromatography medium, Capto Core700 could more effectively remove process-related impurities such as HCP, HCD and total protein without affecting the recovery rate of viral antigen. This study provided reference for the development of purification technology in the production of H5N1 influenza virus vaccine in MDCK cells.
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Autologous serum skin test (ASST) is commonly used as a screening test to assess immune subtypes of chronic spontaneous urticaria (CSU) in clinical practice, but its immunological mechanisms and associations with clinical features and prognosis of CSU are not yet clear. Studies have shown that positive ASST is associated with increased immunoglobulin G autoantibodies, decreased eosinophil and basophil counts, increased CD63 expression on basophils, and changes in circulating inflammatory cytokine levels in CSU patients, but not associated with age, disease duration, and personal or family history of CSU patients, and may be a predictor of severity of chronic urticaria. ASST-positive patients may respond poorly to second-generation H1 antihistamines, slowly to omalizumab, but respond well to cyclosporine and autologous whole blood/serum injections. This review summarizes the immunological and clinical characteristics of ASST-positive patients, and discusses the predictive value of positive ASST for the efficacy of different treatment regimens.
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Objective:To investigate the relationship between early international normalized ratio(INR)and overanticoagulation in elderly patients with atrial fibrillation(AF)treated with Warfarin, and to evaluate its clinical value in predicting overanticoagulation.Methods:A total of 470 elderly patients with AF treated with Warfarin for anticoagulation were enrolled retrospectively.INR was detected in the morning of the next day after 3 days and 7 days of Warfarin treatment.According to whether INR was greater than 3.0 after 7 days of Warfarin treatment, the patients were divided into over-anticoagulation group(n=107)and non-over-anticoagulation group(n=363). The general clinical data of the two groups were analyzed.The receiver operating characteristic curve(ROC)was used to evaluate the value of 3-day INR(early INR)level in predicting overanticoagulation.Logistic regression was used to analyze the factors related to overanticoagulation in elderly AF patients receiving Warfarin treatment.Results:The age, initial warfarin dose, early INR and serum aspartate transferase level in the over-anticoagulation group were higher than those in the non-over-anticoagulation group( P<0.05 for all). The proportions of patients with initial Warfarin dose≥2.5 mg, age≥70 years old, body weight≤65 kg, valvular atrial fibrillation, hypoproteinemia, abnormal liver function, and combined use of antibiotics were higher in the over-anticoagulation group than those in the non-over-anticoagulation group( P<0.05 for all). The body weight, serum albumin level and the proportion of diabetes mellitus in the over-anticoagulation group were lower than those in the non-over-anticoagulation group( P<0.05). ROC curve showed that the area under the curve(AUC)of early INR in predicting over-anticoagulation was 0.927(95% CI: 0.900-0.949, P<0.0001), the sensitivity was 82.86% and the specificity was 88.43%, the optimal cutoff value for predicting overanticoagulation was INR≥1.66.Multiple Logistic regression analysis showed that early INR level≥1.66( OR=33.871, P<0.001), initial warfarin dose≥2.5 mg( OR=17.062, P=0.011), body weight≤65 kg( OR=2.824, P=0.002), age≥70 years old( OR=2.678, P=0.003), and abnormal liver function( OR=2.091, P=0.022)were related factors for over-anticoagulation in elderly patients with atrial fibrillation. Conclusions:Early INR level is closely related to overuse of anticoagulation in elderly AF patients receiving Warfarin treatment, which can be regarded as a predictor of overuse of anticoagulation.Early INR level in elderly AF patients receiving warfarin treatment should be monitored to reduce the incidence of anticoagulant overuse.
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Objective:To evaluate the clinical effects of adjustable traction skin stretchers used in repair of wounds at the lower leg, foot and ankle.Methods:A retrospective study was performed to analyze the clinical data of 56 patients who had been treated for skin defects at the lower leg, foot and ankle from August 2016 to September 2022 at The First Affiliated Hospital of Zhengzhou University, Honghui Hospital, Affiliated to Xi'an Jiaotong University Medical College, The First Affiliated Hospital of Henan Polytechnic University, and Yunnan Zhongde Orthopedic Hospital. There were 35 males and 21 females, aged (39.9±18.7) years. There were 43 traumatic wounds, 3 burns, 6 inflammatory wounds, 3 relief incisions due to osteofascial compartment syndrome, and 1 scar. The areas of skin defect ranged from 2.5 cm × 2.0 cm to 20.0 cm × 10.0 cm. The duration of wounds was (8.6±7.8) d. All the wounds were repaired with adjustable traction skin stretchers. The row-hook type of skin stretchers was used in 28 cases, the single-rod type in 20 cases, the single-rod type combined with an external fixator in 5 cases, and a combination of the row-hook type and the single-rod type in 3 cases.The time for wound traction closure, color of wound skin margin, skin swelling around the wound, functional recovery of affected limb and complications were recorded.Results:The time from skin stretching to wound closure was (7.8±3.8) d in the 56 patients. The color of wound skin edge after stretching was normal in 16 cases, dark red in 38 cases, and dark in 2 cases; the skin swelling around the wound was degree 1 in 21 cases, degree 2 in 33 cases, and degree 3 in 2 cases. The 56 patients were followed up for (8.9±4.1) months. Primary wound closure was achieved in 48 patients, and secondary wound closure in 8 patients after repair with an autologous skin graft. Partial skin necrosis occurred due to tension blisters after skin stretching in 2 patients, one of whom was repaired with an autologous skin graft and the other of whom by dressing change. Deep bone infection recurred in 2 patients whose wounds healed after their bone defects were repaired using Ilizarov technique of bone transfer. In the 56 patients, the muscle strength of the lower extremity beyond the wound was recovered to normal, and the range of motion of the joints adjacent to the wound also recovered to normal.Conclusion:In repair of wounds at the lower leg, foot and ankle, adjustable traction skin stretchers can lead to fine clinical effects and limited complications, because the stretchers can control the tension of skin digitally and precisely.
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Objective:To understand the incidence of sleep disorder in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients before antiviral therapy, and to explore its risk factors.Methods:200 newly treated HIV/AIDS patients who visited the Eighth Affiliated City Hospital of Guangzhou Medical University from January to June 2016 were randomly selected. According to the Pittsburgh Sleep Quality Index (PSQI), they were divided into a good sleep group and a Sleep disorder group; The influencing factors of sleep disorder in HIV/AIDS patients were analyzed by univariate analysis and multivariate logistic regression.Results:The incidence of Sleep disorder in 200 HIV/AIDS patients before antiviral therapy was 22.5%(45/200); CD4 + T cell count was (414.13±202.16)/μl; 29%(58/200) of patients had CD4 + T cell counts<200/μl. There were significant differences in CD4 + T cell count and the proportion of patients with syphilis infection, comorbidity anxiety and comorbidity depression between the good sleep group and the Sleep disorder group (all P<0.05). Multivariate logistic regression analysis showed that syphilis infection ( OR=4.606; 95% CI: 1.973-10.752; P<0.001), comorbidity anxiety ( OR=2.496; 95% CI: 1.086-5.737; P=0.031) and comorbidity depression ( OR=2.087; 95% CI: 0.915-4.760; P=0.040) were risk factors for sleep disorder in HIV/AIDS patients before antiviral treatment. Conclusions:The incidence of Sleep disorder in HIV/AIDS patients before antiviral therapy in Guangzhou is high, especially in patients with syphilis infection, comorbidity anxiety and comorbidity depression. The sleep disorder of HIV/AIDS patients should be assessed and detected early, and multiple interventions should be taken to improve sleep quality.
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Objective:To establish a quantitative real-time PCR detection system for Brucella S2 vaccine strain. Methods:Based on the differences in the entire genome sequence between Brucella S2 vaccine strain and other reference strains of Brucella, primers and probes were designed to establish a quantitative real-time PCR detection system for Brucella S2 vaccine strain. The DNA of 22 reference strains of Brucella and 8 non- Brucella control strains were obtained from the National Institute for Infectious Disease Control and Prevention of the Chinese Center for Disease Control and Prevention. At the same time, environmental samples were obtained from the brucellosis vaccine manufacturers, and bacterial DNA from environmental samples was extracted using a blood/tissue genomic DNA extraction kit. The obtained DNA was pre-amplified by conventional PCR, and then subjected to quantitative real-time PCR secondary amplification (nested fluorescence quantitative PCR) using the amplified PCR product as a template. The specific fluorescence curve and corresponding number of cycles (Ct value) were observed, and the sensitivity was tested. Results:The quantitative real-time PCR detection system established did not detect specific fluorescence curves (without Ct values) for 21 reference strains of Brucella and 8 non- Brucella control strains, except for S2 vaccine strains. The established detection system had a minimum detection limit of 4.34 fg (genomic DNA) for detecting the DNA of Brucella S2 vaccine strain; DNA of Brucella S2 vaccine strain was detected in 3 of the 14 environmental samples collected. Conclusion:The quantitative real-time PCR detection system established can detect Brucella S2 vaccine strain in samples, with good sensitivity and specificity.
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Objective:A nested-PCR assay is developed to detect and identify the genomic DNA of Brucella vaccine A19 strain. Methods:The whole genomic sequences of Brucella vaccine A19 strain and other Brucella spp. strains were compared and analyzed. The primers were designed by nucleotide difference sites. The nested-PCR assay was established to detect and identify Brucella vaccine A19 strain. The genomic DNA of Brucella vaccine A19 strain was extracted and diluted. The diluted template DNA was tested for sensitivity of using nested-PCR assay. And the specificity of nested-PCR assay was tested for the genomic DNA of other Brucella spp. strains and non- Brucella spp. strains. Results:The minimum detection limit of the nested-PCR assay was 3.43 fg. The nested-PCR assay established for amplification of Brucella vaccine A19 strain showed 246 bp electrophoresis bands, while other Brucella spp. strains showed 314 bp electrophoresis bands, and non- Brucella spp. strains did not produce electrophoresis bands. Conclusions:The nested-PCR assay established has the characteristics of high sensitivity and specificity. It can be detected when there is one copy of Brucella vaccine A19 strain genomic DNA in the reaction system. This method is particularly suitable for the detection and identification of trace genomic DNA of Brucella vaccine A19 strain in sample.
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@#Objective To compare and analyze the therapeutic effects of robot-assisted lobectomy and segmentectomy for stage ⅠA non-small cell lung cancer with a diameter≤2 cm. Methods A total of 181 patients with pathologically confirmed stage ⅠA non-small cell lung cancer (diameter≤2 cm) who underwent robot-assisted lobectomy and segmentectomy in our hospital from 2018 to 2021 were included. There were 74 males and 107 females with an average age of 57.50±10.60 years. They were divided into two groups according to the surgical procedure: a segmentectomy group (85 patients) and a lobectomy group (96 patients). Results There was no statistically significant difference between the two groups in terms of clinical data such as age, gender, smoking history, basic disease, pathological type, tumour diameter, operative time, postoperative 24 h drainage volume and overall complications (P>0.05). The intraoperative blood loss (33.88±16.26 mL vs. 39.27±19.48 mL, P=0.046), groups of dissected lymph nodes (4.76±1.19 vs. 5.52±1.46, P=0.000), number of dissected lymph nodes (14.81±7.23 vs. 18.06±7.70, P=0.004) and postoperative 72 h drainage volume (561.65±225.31 mL vs. 649.84±324.34 mL, P=0.037) of patients in the segmentectomy were less than those in the lobectomy group. The chest drainage time (5.49±3.92 d vs. 7.60±4.96 d, P=0.002) and postoperative hospital stay time (7.47±4.16 d vs. 9.67±5.50 d, P=0.003) were shorter than those in the lobectomy group. There was no conversion to thoracotomy or perioperative death in the two groups. The postoperative follow-up rate was 100.0% with a longest follow-up time of 48 months. The 3-year recurrence-free survival rates of the segmentectomy group and lobectomy group were 87.7% and 92.4%, respectively (P=0.465). Conclusion The da Vinci robot-assisted lobectomy and segmentectomy are safe and feasible surgical procedures for patients with stage ⅠA non-small cell lung cancer (diameter≤2 cm), with a similar 3-year recurrence-free survival rate. The lobectomy group has more lymph nodes dissected, while the segmentectomy group is superior to the lobectomy group in terms of intraoperative blood loss, postoperative 72 h chest drainage volume, chest drainage time and postoperative hospitalization time.
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The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.
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Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.
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Objective:To investigate the characteristics of wideband acoustic immittance（WAI） measurements in patients with unilateral Ménière's disease（MD） and evaluate the clinical value of WAI in diagnosis of MD. Methods:WAI was performed in 30 patients with unilateral MD（30 ears for symptomatic and 30 ears for asymptomatic） and in 26 healthy individuals（52 ears）（control group）. The WAI measurements, including the frequency first appearing two peaks in energy absorbance（EA） tympanogram, resonance frequency（RF）, the peak value of absorbance（PVA）, the integral area of absorbance（IAA）, EA curve at peak pressure, were analyzed. Results:①The occurrence of two peaks in EA tympanogram in both the MD symptomatic and asymptomatic ear was observed in 27 ears（84.4%）, and 38 ears（70.4%） in the control group, with no significant difference in the frequency of first appearing in two peaks onset between the groups（all P>0.05）. ②The RF of the MD symptomatic ears was significantly lower than that of the asymptomatic ears（t=-3.544, P=0.001） and that of the control subjects（t=2.084, P=0.041）; there was no difference of RF between the MD asymptomatic ears and the control group（P>0.05）. ③The PVA were significantly lower in both MD symptomatic（t=4.240, P<0.01） and asymptomatic ears（t=4.202, P=0.001） than in controls. ④The IAA in MD symptomatic（t=3.295, P=0.001） and asymptomatic ears（t=3.193, P=0.003） was significantly lower than in the control group. ⑤Comparison of the EA curve at peak pressure of the three groups: the EAs of MD symptomatic ears were lower than those of the control group at the range of 1 059-2 911 Hz（all P<0.05）; the EAs of MD symptomatic ears were lower than those of MD asymptomatic ears within 1 000 Hz and 1 834-2 119 Hz（all P<0.05）; the EAs of MD asymptomatic ears were lower than those of the control group at the range of 515-2 748 Hz（all P<0.05）. Conclusion:Symptomatic ears in unilateral MD patients show alterations in some WAI measurements compared to asymptomatic ears and/or controls, suggesting that middle ear mechanical fuction of the affected side may be modified due to the endolymphatic hydrops. The clinical significance of WAI needs to be further explored in the context of evaluating MD.