The evolution and application progress of non-modified drug target discovery CETSA technology / 药学学报

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Compatibility Theory of Yiqi Zengmian Prescription as Vaccine Adjuvant / 中国实验方剂学杂志

ObjectiveThis study explored the application of Yiqi Zengmian prescription as a vaccine adjuvant， aiming to provide a new scheme for the prevention and control of corona virus disease 2019（COVID-19） with traditional Chinese medicine （TCM）. By analyzing the compatibility and efficacy， this paper examines the compatibility effect of Yiqi Zengmian prescription， which is modified from the classic tonifying agent Si Junzitang， as a vaccine adjuvant. MethodUsing the Database of Ancient Classical Prescriptions， this paper analyzed the composition of Yiqi Zengmian prescription and probed into the theoretical basis for the compatibility of this prescription from the properties， medicine combination， and efficacy. Furthermore， the compatibility effect of this prescription with vaccines was analyzed. ResultAs a TCM prescription， Yiqi Zengmian prescription focuses on the lung and spleen and enhances the Qi in the two organs. The lung governs Qi movement. The body breathes fresh air through the lungs and exchanges the turbid gas in the lungs， and the gas circulates alternately in the lungs to ensure the normal breathing of the human body. The spleen governing transportation and transformation is the hub for Qi movement， and Qi is the embodiment of metabolic function. By regulating qi movement and enhancing the functions of Qi and blood， Yiqi Zengmian prescription can enhance the immunogenicity of the vaccine， which provides a theoretical basis for enhancing the immune effects of vaccines. ConclusionYiqi Zengmian prescription has the effects of replenishing Qi and invigorating spleen， regulating Qi and drying dampness， and enhancing immunity. The in-depth analysis of the TCM theory of Yiqi Zengmian prescription as a vaccine adjuvant and the results of clinical and laboratory studies suggest that Yiqi Zengmian prescription may enhance the induction of immune response after vaccination and maintain the immune memory. However， the mechanism of Yiqi Zengmian prescription in regulating the complex immune network remains to be elucidated.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Tumor perfusion enhancement effect combined with programmed cell death-Ligand 1 antibody improves the immune microenvironment of solid tumors / 中华超声影像学杂志

Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.

Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023) / 中华创伤杂志

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures (version 2023) / 中华创伤杂志

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture (version 2023) / 中华创伤杂志

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Application progress of ultrasound examination in the diagnosis and treatment of breast cancer / 中国基层医药

Breast cancer ranks first in incidence in female malignant tumors, which obviously endangers patients' health. There is an increasing number of young female patients with breast cancer. If a breast lump is discovered early, and its benign or maligant nature can be identified, then the patient can be treated in time, and therefore the risk of breast cancer death can be greatly reduced. In recent years, with the continuous development of contrast-enhanced ultrasound and other technologies, breast cancer diagnosis is increasing, which provides an auxiliary role for clinical treatment. This review summarizes ultrasound examination, in particular contrast-enhanced ultrasound, for diagnosis and treatment of breast cancer and helps provide evidence for clinical treatment of this disease

Genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province / 中华地方病学杂志

Objective:To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province, and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods:Venous blood samples were collected from 44 849 people of childbearing age in hospitals in Hubei Province from May 13, 2019 to August 17, 2021. PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes. Spouses of those who tested positive were also tested for thalassemia genes. When both spouses carried the same type of thalassemia gene, the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results:Among the 44 849 people of childbearing age, 2 286 cases were diagnosed as thalassemia gene carriers through genetic testing, and the total detection rate was 5.10% (2 286/44 849). Among them, 1 488 cases were diagnosed as α-thalassemia, and the detection rate was 3.32% (1 488/44 849); 767 cases were diagnosed as β-thalassemia, and the detection rate was 1.71% (767/44 849); 31 cases were diagnosed as α-thalassemia combined with β-thalassemia, and the detection rate was 0.07% (31/44 849). The top three genotypes of α-thalassemia were -α 3.7/αα, -- SEA/αα, and -α 4.2/αα, accounting for 58.06% (864/1 488), 26.14% (389/1 488), and8.74% (130/1 488), respectively. The top three genotypes of β-thalassemia were β IVS-Ⅱ-654/β N, β CD41-42/β N, and β CD17/β N, accounting for 41.72% (320/767), 21.25% (163/767), and 16.04% (123/767), respectively. The main genotypes of α-thalassemia combined with β-thalassemia were -α 3.7/αα complex β IVS-Ⅱ-654/β N and -α 3.7/αα complex β CD41-42/β N, accounting for 29.03% (9/31) and 16.13% (5/31), respectively. A total of 59 people of childbearing age were conducted prenatal diagnosis, among fetus, there were 4 cases of severe thalassemia (2 cases of severe α-thalassemia, 2 cases of severe β-thalassemia), 5 cases of intermediate α-thalassemia, 5 cases of intermediate or severe β-thalassemia, 19 cases of mild thalassemia (8 cases of mild α-thalassemia, 11 cases of mild β-thalassemia), 13 cases of stationary α-thalassemia, and 1 case of stationary α-thalassemia combined with mild β-thalassemia, there were 12 cases without α-thalassemia or β-thalassemia genes. After follow-up, 4 cases of severe thalassemia, 2 cases of intermediate α-thalassemia, and 5 cases of intermediate or severe β-thalassemia were terminated pregnancy by the joint decision of both parents. Conclusions:In Hubei Province, the detection rate of thalassemia is high, and α-thalassemia is the main mutation type. The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.

Changes of Macular Microcirculation After Near Work in Myopic Patients / 中山大学学报(医学科学版)

ObjectiveTo compare the changes of retinal microcirculation indexes in the anterior and posterior macular areas of the eyes used at close range and to explore the possible causes of myopia affected by near work. MethodsWatching mobile phone video for 1 hour at close range was used as the method of defining near work. The OCTA technology was used to measure the superficial retinal microcirculation indexes within 6 by 6 mm macular area before and after near work， including the superficial retinal VLD from the nerve fiber layer to the inner boundary of the outer plexiform layer， the VPD， nonperfusion area of FAZ， FAZ-P and FAZ circulation，. The FAZ was divided int center， inner layer， outer layer and overall according to the region， and 11 microcirculation indexes were obtained to compare the differences between before and after near work. ResultsThe indexes of superficial retinal microcirculation in the macular area generally decreased after near work， except for FAZ-A and FAZ-P（P = 0.148， 0.975）. The largest differences among both VLD and VPD occurred between the central and inner layer（Difference = 1.00， 0.80， 0.02， 0.02，P = 0.001， 0.008， 0.001， 0.008）. No differences in microcirculation indexs were observed in the macular area after near work with different diopters and axial lengths. ConclusionNear work may affect the occurrence and development of myopia by affecting the changes of retinal microcirculation in the superficial layer of macula， leading to ischemia and hypoxia.

Myosin Heavy Chain 7 Gene-derived miRNA-208b-3p Enhances the Fibrosis-related Gene Expression in Cardiac Fibroblasts / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of myosin heavy chain 7 gene-derived miRNA-208b-3p on the fibrotic phenotype of cardiac fibroblasts. MethodsmiRNA chip array was performed to detect the dysregulated miRNAs in the myocardium of diabetic db/db mice and db/m control mice. Neonatal mouse ventricular cardiomyocytes （NMVCs） and cardiac fibroblasts （CFs） were isolated from C57BL/6 mice and cultured. Real-time quantitative PCR （RT-qPCR） was conducted to determine the expression of miR-208b-3p in mouse CFs and NMVCs subjected to angiotensinⅡ（AngⅡ） and high glucose plus glucose oxidase （G/Go） treatment， respectively. Cell counting kit 8（CCk8） assay， flow cytometry and determination of fibrosis-related protein， including COL1A1， COL3A1and α-SMA， were performed in mCFs transfected with miR-208b-3p. Dual luciferase reporter assay was performed to confirm the interaction between miR-208b-3p and the 3'-UTR of metal response element binding transcription factor 2 （Mtf2） and progesterone receptor membrane component 1（Pgrmc1）， respectively. The expressions of Mtf2 and Pgrmc1 at the mRNA and protein levels in mCFs after miR-208b-3p mimic transfection were determined using RT-qPCR and Western blot assay， respectively. The small interfering RNA （siRNA） was used to inhibit Mtf2 and Pgrmc1 expression in mCFs， and the effects of Mtf2 siRNA， Pgrmc1 siRNA and miR-208b-3p on fibrosis-related protein expression in mCFs were investigated. ResultsResults of miRNA chip array and RT-qPCR assay showed that miR-208b-3p was up-regulated in the myocardium of the diabetic db/db mice. miR-208b precursor and the host gene of Myh7 were consistently increased in db/db mice. miR-208b-3p and Myh7 mRNA were expressed in mCFs and NMVCs， but the levels of miR-208b-3p and Myh7 mRNA in NMVCs were much higher than those in mCFs. miR-208b-3p was up-regulated in mCFs and NMVCs subjected to Ang Ⅱ and G/Go treatment， respectively. miR-208b-3p could significantly enhance fibrosis-related protein， including COL1A1， COL3A1 and α-SMA， in mCFs， without affecting the proliferation activity and cell cycle distribution of mCFs. Dual luciferase reporter assay revealed the interactions of miR-208b-3p with the 3'-UTR of Mtf2 and Pgrmc1. The results of RT-qPCR and Western blotting confirmed that miR-208b-3p inhibited Mtf2 and Pgrmc1 expression at the post- transcriptional level. Transfection with miR-208b-3p mimic， Mtf2 siRNA and Pgrmc1 siRNA could consistently enhance the fibrosis-related protein expression in the cardiac fibroblasts. ConclusionsmiR-208b-3p enhances fibrosis-related gene expression by targeting Mtf2 and Pgrmc1in mCFs.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Background@#Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. @*Methods@#We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. @*Results@#In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. @*Conclusion@#This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Postoperative corneal topography generation based on attention mechanism and Pix2Pix network / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the use of attention mechanism and Pix2Pix generative adversarial network to predict the postoperative corneal topography of age-related cataract patients undergone femtosecond laser arcuate keratotomy.METHODS:In this retrospective case series study, the 210 preoperative and postoperative corneal topographies from 87 age-related cataract patients(105 eyes)undergoing femtosecond laser arcuate keratotomy at Shanxi Eye Hospital between March 2018 and March 2020 were selected and divided into a training set(180)and a test set(30)for model training and testing. The peak signal-to-noise ratio(PSNR), structural similarity(SSIM)and Alpins astigmatism vector analysis were used to compare the accuracy of postoperative corneal topography prediction under different attention mechanisms.RESULTS:The model based on attention mechanism and Pix2Pix network can predict postoperative corneal topography, among which the model based on Self-Attention mechanism has the best prediction effect, with PSNR and SSIM reaching 16.048 and 0.7661, respectively. There were no statistically significant differences in the difference vector, difference vector axis position, surgically induced astigmatism, and correction index between real and generated corneal topography on the 3mm and 5mm rings(all P&#x003E;0.05).CONCLUSION:Based on the Self-Attention mechanism and Pix2Pix network, the postoperative corneal topography can be well predicted, which can provide reference for the surgical planning and postoperative effects of ophthalmic clinicians.

Research progress on hypertension related frailty in the elderly / 公共卫生与预防医学

Hypertension is currently the most common chronic disease in the elderly, and frailty is a non-specific state in which vulnerability of the body increases and anti-stress ability decreases due to physiological reserve function decline. A series of clinical adverse events may occur in elderly people with frailty when there is a small stimulus. Frailty and hypertension often coexist in the elderly. Relevant guidelines for diagnosis and treatment recommend that elderly patients with hypertension should be evaluated for frailty when using antihypertensive drugs. The risks and benefits of antihypertensive treatment should be evaluated according to the patient's physiological reserves, thereby helping to choose personalized antihypertensive treatment, determining appropriate antihypertensive goals, and improving the management of elderly hypertension. Herein, the research progress on hypertension related frailty in the elderly is reviewed to provide reference for personalized treatment of elderly patients with hypertension.

Current research status of prognostic models for transjugular intrahepatic portosystemic shunt / 临床肝胆病杂志

Transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective method for the treatment of portal hypertension complications in patients with decompensated liver cirrhosis. At present, there are many prognostic scoring tools for risk stratification of poor prognosis after TIPS. This article briefly introduces seven prognostic scoring tools commonly used for TIPS and summarizes the clinical research evidence of each scoring tool. The literature review shows that there is currently no sufficient research evidence to determine the optimal prognostic scoring tool after TIPS. Future clinical studies should comprehensively explore the advantages and disadvantages of different scoring tools in predicting short- and long-term adverse prognostic events after TIPS and develop new prognostic scoring tools in combination with new prognostic markers.

Mechanism of rhynchophylline solid lipid nanoparticles inhibiting the proliferation of airway smooth muscle cells in asthmatic model mice / 中国药房

OBJECTIVE To study the inhibitory effect mechanism of rhynchophylline solid lipid nanoparticles （Rhy-SLN） on the proliferation of airway smooth muscle cells （ASMCs） in asthmatic model mice. METHODS Asthma model was prepared by ovalbumin+calmogastrin sensitization. The primary isolation and culture of ASMCs were performed， and morphological observation and identification were also conducted [when α -smooth muscle actin （α -SMA） appeared red and Desmin appeared green in ASMCs， indicating successful cultivation of ASMCs]. The cells were divided into blank group （ASMCs of normal mice）， model group （ASMCs of asthma model mice）， Rhy-SLN group （ASMCs of asthma model mice）， recombinant suppressors of cytokine signaling 1 （SOCS1） overexpression group （ASMCs of asthma model mice transfected with SOCS1 vector）， SOCS1-RNAi group （ASMCs of asthma model mice transfected with SOCS1-RNAi vector） and SB203580 group [p38 mitogen-activated protein kinase （p38 MAPK） inhibitor， ASMCs of asthma model mice]. The cells of each group were added into the corresponding culture medium containing drug （10 μmol/L） or not containing drug for 24 hours. MTT method was used to detect the proliferation of ASMCs in asthmatic mice； Western blot assay was used to detect the protein expressions of α-SMA， interleukin-1β （IL-1β）， SOCS1， p38 MAPK and phosphorylated p38 MAPK （p-p38 MAPK） in ASMCs. RESULTS The primary ASMCs of mice varied in shape and size， presenting irregular， spindle and triangular shapes；α-SMA appeared red and Desmin appeared green， indicating successful cultivation of ASMCs. Compared with model group， ASMCs absorbance values and protein expressions of α -SMA， p38 MAPK， and p-p38 MAPK were reduced significantly in Rhy- SLN group， SOCS1 overexpression group and SB203580 E-mail：wangmeng106@163.com group， while protein expression of SOCS1 （except for group） was increased significantly （P＜0.05）； protein expressions of IL-1β was reduced significantly in ASMCs （P＜ 0.05）. ASMCs absorbance values and protein expressions of α-SMA， SOCS1， p38 MAPK and p-p38 MAPK were increased significantly in SOCS1-RNAi group （P＜0.05）. CONCLUSIONS Rhy-SLN can inhibit the proliferation of ASMCs， the mechanism of which may be associated with overexpression of SOCS1 and inhibiting the protein expressions of IL-1β and p38 MAPK.

Role of A-kinase anchor protein 12 in chronic liver diseases / 临床肝胆病杂志

A-kinase anchor protein 12 (AKAP12) is a scaffold protein that improves the specificity and efficiency of spatio-temporal signals by assembling intracellular signal proteins into specific complexes. In recent years, the role of AKAP12 in chronic liver diseases has attracted more and more attention. This article introduces the physiological functions of AKAP12 and reviews the role of AKAP12 in chronic liver diseases, in order to lay a foundation for the use of AKAP12 small molecule as a new therapeutic target for chronic liver diseases.

Effect of co-morbid chronic kidney disease on the accuracy of cardiac troponin levels for diagnosis of acute myocardial infarction / 南方医科大学学报

OBJECTIVE@#To evaluate the accuracy of cardiac troponin (cTn) levels in the diagnosis of acute myocardial infarction (AMI) in patients with chronic kidney disease (CKD) and explore a potential strategy for improving the diagnostic accuracy.@*METHODS@#We retrospectively analyzed the data from patients with high-risk chest pain admitted in Zhujiang Hospital from January, 2018 to December, 2020, including 126 patients with and 272 patients without CKD, and 122 patients diagnosed to have AMI and 276 patients without AMI. The baseline clinical data of the patients and blood test results within 12 h after admission were collected.@*RESULTS@#In patients without AMI, cTnT level was significantly higher in those with co-morbid CKD than in those without CKD (P < 0.001), and showed a moderate negative correlation with eGFR (rs=- 0.501, P < 0.001), while cTnI level did not differ significantly between the two groups (P=0.72). In patients with CKD, the optimal cutoff level was 0.177 μg/L for cTnT and 0.415 ng/mL for cTnI for diagnosis of AMI, for which cTnI had a higher specificity than cTnT. The diagnostic model combining both cTnT and cTnI levels [P=eY/(1+ eY), Y=6.928 (cTnT)-0.5 (cTnI)-1.491] had a higher AUC value than cTn level alone.@*CONCLUSION@#In CKD patients, the cutoff level of cTn is increased for diagnosing AMI, and cTnI has a higher diagnostic specificity than cTnT. The combination of cTnT and cTnI levels may further improve diagnostic efficacy for AMI.