Advances in Salmonella-mediated targeted tumor therapy / 药学学报

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

Mutation-associated transcripts reconstruct the prognostic features of oral tongue squamous cell carcinoma / 国际口腔科学杂志·英文版

Tongue squamous cell carcinoma is highly malignant and has a poor prognosis. In this study, we aimed to combine whole-genome sequencing, whole-genome methylation, and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better. Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methylated loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Collectively, changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.

Construction of an epileptic seizure prediction model using a semi-supervised method of generative adversarial and long short term memory network combined with Stockwell transform / 南方医科大学学报

OBJECTIVE@#To propose a semi-supervised epileptic seizure prediction model (ST-WGAN-GP-Bi-LSTM) to enhance the prediction performance by improving time-frequency analysis of electroencephalogram (EEG) signals, enhancing the stability of the unsupervised feature learning model and improving the design of back-end classifier.@*METHODS@#Stockwell transform (ST) of the epileptic EEG signals was performed to locate the time-frequency information by adaptive adjustment of the resolution and retaining the absolute phase to obtain the time-frequency inputs. When there was no overlap between the generated data distribution and the real EEG data distribution, to avoid failure of feature learning due to a constant JS divergence, Wasserstein GAN was used as a feature learning model, and the cost function based on EM distance and gradient penalty strategy was adopted to constrain the unsupervised training process to allow the generation of a high-order feature extractor. A temporal prediction model was finally constructed based on a bi-directional long short term memory network (Bi-LSTM), and the classification performance was improved by obtaining the temporal correlation between high-order time-frequency features. The CHB-MIT scalp EEG dataset was used to validate the proposed patient-specific seizure prediction method.@*RESULTS@#The AUC, sensitivity, and specificity of the proposed method reached 90.40%, 83.62%, and 86.69%, respectively. Compared with the existing semi-supervised methods, the propose method improved the original performance by 17.77%, 15.41%, and 53.66%. The performance of this method was comparable to that of a supervised prediction model based on CNN.@*CONCLUSION@#The utilization of ST, WGAN-GP, and Bi-LSTM effectively improves the prediction performance of the semi-supervised deep learning model, which can be used for optimization of unsupervised feature extraction in epileptic seizure prediction.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway / 中国中药杂志

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.

Comparing the predictive value of parameters extracted from circular ROIs with whole liver histogram on Gd-EOB-DTPA enhanced MRI for postoperative liver failure in focal liver lesions / 中华肝胆外科杂志

Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.

The occurrence and progress of immune inflammatory response involved in gastroesophageal reflux disease / 中国医师进修杂志

Objective:To investigate the role of immune and inflammatory responses in the pathogenesis of gastroesophageal reflux disease (GERD).Methods:Fifteen patients with GERD who underwent biopsy and histopathology during painless gastroscopy in the digestive endoscopy center of the General Hospital of the PLA from December 2018 to September 2019 were analyzed retrospectively. They were divided into three groups: 6 cases of non erosive reflux disease (NERD), 8 cases of reflux esophagitis (RE) and 1 case of RE with high-grade intraepithelial neoplasia (RE-HIN). HE staining was used to analyze the inflammatory reaction of each group. The expression of cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, myeloperoxidase (MPO), IL-4, nuclear factor kappa-B(NF-κB), IL-8, reactive oxygen species (ROS-1) were monitored by immunohistochemistry. Chi square test was used to analyze the positive rate of immune and inflammatory indexes in each group.Results:The three groups showed mild and moderate inflammatory cell infiltration, mostly lymphocyte infiltration, and basal cell hyperplasia in 3 cases. There was no significant difference between inflammatory cell infiltration, basal hyperplasia and inflammatory grade in NERD and RE( P>0.05). Immune and inflammatory factors COX-2(positive rate:NERD 4/6, RE4/8, RE-HIN 1/1), iNOS(positive rate:NERD 4/6, RE 3/8, RE-HIN 0), IL-1β(positive rate:NERD 6/6, RE 7/8, RE-HIN 1/1), MPO(positive rate:NERD 4/6, RE 7/8, RE-HIN 1/1), IL-4(positive rate:NERD 3/6, RE 4/8, RE-HIN 0), IL-8(positive rate:NERD 2/6, RE 6/8, RE-HIN 1/1), ROS-1(positive rate:NERD 3/6, RE 1/8, RE-HIN 0) and signal pathway NF- κ B (positive rate:NERD 4/6, RE 8/8, RE-HIN 1/1) were positive in three groups. The expressions of IL-1β, MPO and NF-κB were statistically significant among the three groups ( P<0.05). Conclusions:There is an inflammatory cascade mediated by immune inflammatory factors and mediators in GERD patients, and NF-κB signaling pathway is involved. It provides a basis for finding targets to block immune and inflammatory responses in the later stage to treat GERD.

What Do Patients Need in the Process of Constructing a Doctor-patient Community with a Shared Future / 中国医学伦理学

Constructing a doctor-patient community with a shared future requires efforts from both the medical supply side and the patient demand side, with special attention to the needs of patients. Continuously meeting and improving the needs of patients is the starting point, ultimate goal, and evaluation standard for constructing a doctor-patient community with a shared future. Therefore, this paper proposed the proposition of "what patients need", that is, what needs do patients have and how to meet their needs. The fundamental needs of patients are to diagnose and treat diseases and recover from illness, which are specifically manifested in the demands to narrate the disease’s feelings, the willingness to participate in medical decision-making, the experience of diagnosis and treatment in the process of medical treatment, and the satisfaction evaluation of the hospital’s performance appraisal. On the basis of clarifying the needs of patients, this paper proposed the paths and methods to meet patients’ needs, and provided new ideas for constructing a doctor-patient community with a shared future.

Current status of animal models of cataract classified by etiology / 国际眼科杂志(Guoji Yanke Zazhi)

Cataract is one of the major causes of vision loss and even blindness in patients, and surgery is the only effective method to treat it. The pathogenesis and precaution of cataract remain hot issues in ophthalmological research. With the maturation of biotechnology in recent years, modeling methods and species of experimental animals have become more diverse, which are still the mainstay of cataract mechanism research. However, the ideal animal model of cataract has yet to be constructed due to the complexity of human cataract etiology. Herein, the modeling principles, in vivo or in vitro modeling methods, characteristics, and existing problems of animal models of cataract are summarized according to etiology, providing the theoretical foundation for the construction of a comprehensive animal model that more closely resembles the human cataract.

The clinical efficacy of all-port robotic versus thoracoscopic lobectomy in stageⅠA non-small cell lung cancer: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To investigate the perioperative efficacy and safety of all-port robotic lobectomy versus thoracoscopic lobectomy in stageⅠA non-small cell lung cancer. Methods    The clinical data of patients with stageⅠA non-small cell lung cancer who underwent lobectomy with lymph node dissection performed by the same operator in our center from June 2019 to June 2022 were retrospectively analyzed. The patients were divided into a robotic group and a thoracoscopic group according to different procedures. We compared the relevant indexes such as operation time, intraoperative bleeding, number of lymph node dissection stations, number of lymph node dissection, postoperative tube time, postoperative hospitalization time, closed chest drainage volume, postoperative pain, postoperative complications and hospitalization cost between the two groups. Results    There were 83 patients in the robotic group, including 34 males and 49 females with a median age of 60.0 (53.0, 67.0) years, and 94 patients in the thoracoscopic group, including 36 males and 58 females with a median age of 60.5 (54.0, 65.3) years. There was no conversion to thoractomy or death in postoperative 90 days in both groups. No statistical difference was seen in the operation time, total postoperative drainage volume and postoperative complication rates between the two groups (P>0.05). Patients in the robotic group had less intraoperative bleeding (P<0.001), more lymph node dissection stations (P=0.002) and numbers (P=0.005), less postoperative pain (P=0.002), and shorter postoperative time with tubes (P=0.031) and hospital stay (P<0.001). However, the surgery was more expensive in the robotic group (P<0.001). Conclusion    All-port robotic surgery is safe and effective for patients with early-stage non-small cell lung cancer with less intraoperative bleeding, more lymph node dissection, less postoperative pain, and shorter hospital stay compared with the thoracoscopic surgery.

Guidelines for Traditional Chinese Medicine Diagnosis and Treatment of Metastatic Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Analysis and thoughts on the settings of sub-campus of public hospitals directly under the National Health Commission of China / 中华医院管理杂志

Objective:To analyse the settings of sub-campus of public hospitals directly under the National Health Commission, so as to provide research reference and suggestions for further promoting the scientific and standardized construction of sub-campuses of public hospitals.Methods:Data before August 30, 2022 were collected from the official websites of the hospitals in question including their introduction, overview, navigation, news and other categories of information.Relevant literatures on multi-campus published by hospitals under the direct management of the National Health Commission were obtained from the China National Knowledge Network, which was identified by searching the keywords " sub or multi-campus hospital" with " author affiliation", using such search conditions as " MeSH major topic" or " title/keywords/abstract" of the studied hospitals in advanced search builder. Descriptive analysis and frequency analysis were conducted on the numbers, the construction reasons, geographical location, operation scale, characteristics and positioning of the sub-campuses in the studied hospitals.Results:Of the 44 such hospitals, 30 had a total of 50 sub-campuses in operation. Generally there were two modes of construction. 35 were newly constructed and 15 formed by mergers; 37 sub-campuses were built and put into operation since 2010. Sub-campuses were usually located in the same area of the main campus, with 11 in the same area of the same city and areas, 35 in different areas of the same city, and 4 in different cities; the average geographical distance between the sub-campus and the main hospital campus was 31.18 kilometers; 27 sub-campuses had beds ≤ 500, 12 sub-campuses had beds between 501-1 000, 11 had beds>1 000; 14 specialized sub-campuses and 31 out of the 35 comprehensive sub-campuses clearly indicating their characteristics of specialized departments, and 1 other (research institute areas with research beds).Conclusions:Future proofing is characteristic of these public hospitals in terms of their sub-campus construction, regional setting, planning and positioning, and functional layout. However, both government regulatory departments and public hospitals should comprehensively consider and make prudent decisions on the planning, investment, demonstration, layout, and other aspects of the construction of sub-campuses of hospitals.

Development and validation of ID-LC-MS/MS method for L-tryptophan and its metabolites / 中华检验医学杂志

Objective:To establish an isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the determination of L-tryptophan and its metabolites in serum.Methods:The methodology was established and evaluated using serum samples collected from 166 healthy subjects undergoing physical examinations at West China Hospital from November 2022 to January 2023 were collected. Isotope-labeled markers of L-tryptophan (Trp), L-kynurenine (Kyn), and kynurenic acid (KA) were used as internal standards. After protein precipitation treatment of serum samples, LC-MS/MS was used to determine Trp, Kyn, and KA simultaneously. The selectivity, specificity, linearity, detection limit (LOD), quantification limit (LOQ), carry-over, precision, recovery rate, matrix effect, and dilution integrity of the method were evaluated.Results:The linearity of Trp, Kyn, and KA was demonstrated to be 0.999. The LODs were 0.10 μmol/L, 0.01 μmol/L and 1.00 nmol/L, respectively. The LOQs were 0.20 μmol/L, 0.04 μmol/L and 2.00 nmol/L, respectively. The intra-batch precision and inter-batch precision were below<10%. The average recovery rate and the relative matrix effect were all about 100%. The samples over the upper limit of quantitation can be diluted up to 16 times. The Trp concentration, Kyn concentration, KA concentration, Kyn/Trp ratio, and KA/Kyn ratio in serum of healthy subjects were 59.55±10.92 μmol/L, 1.85±0.43 μmol/L, 39.89±17.93 nmol/L, (31.64±8.19)×10 -3 and 21.51±6.72, respectively. Conclusion:An ID-LC-MS/MS method was successfully established for the quantitative determination of Trp, Kyn, and KA in serum. The method proved to be simple, rapid, sensitive, accurate, and reliable, providing robust support for clinical research related to these analytes.

Study on the relationship between serum cytokines levels after chimeric antigen receptor (CAR)-T cell immunotherapy and the prognosis of bridged allogeneic hematopoietic stem cell transplantation in acute B lymphoblastic leukemia patients / 中华检验医学杂志

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Epidemiological investigation and genomic characterization of the first case of fever with thrombocytopenia syndrome in Puyang / 中华微生物学和免疫学杂志

Objective:To report the first case of sever fever with thrombocytopenia syndrome caused by severe fever with thrombocytopenia syndrome virus (SFTSV) in Puyang city, and to study the epidemiological and molecular characteristics of S, M, L fragments of the SFTSV isolate.Methods:The epidemiological characteristics of this case was analyzed with epidemiological methods. SFTSV was isolated from the patient′s serum sample. Nucleic acid of SFTSV was extracted and detected by fluorescent RT-PCR. A multiplex PCR method was constructed to amplify the nucleic acid sequence of the virus. whole-genome sequencing was performed on the next-generation sequencing platform. MEGA11 and DNAStar was used for homology analysis and a phylogenetic tree was constructed.Results:Epidemiological investigation showed that the patient and his close contacts had no history of travel or tick bite within 14 d, but had a history of fieldwork. The patient′s serum sample was positive for SFTSV nucleic acid. Genetic analysis showed that the S, M, L gene fragments of the first SFTSV isolate in Puyang belonged to genotype E. This isolate shared 94.8%-99.6%, 94.0%-99.8% and 95.7%-99.7% nucleotide sequence homology with the representative strains acquired from GeneBank in S, M, L gene fragments, respectively.Conclusions:This case was the first case of SFTSV-caused severe fever with thrombocytopenia syndrome in Puyang. The SFTSV isolate shared a close homology with domestic isolates, but its genotype was significantly different from the SFTSV strains isolated in Henan in recent years, indicating that it might an imported case from other places in Henan Province or Hubei Province. Disease monitoring and professional training for medical personnel should be strengthened and more attention should be paid to the evolution and mutation of SFTSV.

Whole-genome characterization and traceability analysis of the first COVID-19 outbreak caused by Omicron variant in Henan Province / 中华微生物学和免疫学杂志

Objective:To analyze the whole genome of Omicron variants causing the first local Omicron outbreak in Henan Province and to investigate the mutations in the SARS-CoV-2 genome for source tracing.Methods:Respiratory tract samples from COVID-19 cases in the Omicron outbreak in Henan Province from January 7 to 29, 2022 were subjected to whole-genome sequencing and sequence alignment analysis. Whole-genome identity, variations and evolution of the Omicron variants were analyzed.Results:Through high-throughput sequencing, the whole-genome sequences of SARS-CoV-2 were obtained from 120 cases, which accounted for 25.64% (120/468) of all COVID-19 cases in Anyang during the same period. Compared with the genome of Wuhan reference strain (NC_045512.2), there were 57-59 nucleotide mutation sites in the 120 whole genome sequences, and one or two nucleotide mutation sites were added to the shared 57 nucleotide sites. All of the 120 strains were VOC/Omicron (BA.1.1) variants and shared high homology. The whole-genome sequence obtained from the first case A contained 57 nucleotide mutation sites, while apart from the 57 identical nucleotide mutation sites, one specific mutation site (C1594T) was found in the whole-genome sequence obtained from the first case B, suggesting that the two cases were in the same transmission chain. After comparing with the database of domestic and imported cases by the Chinese Center for Disease Control and Prevention and the Henan Provincial Center for Disease Control and Prevention, it was found that the current outbreak was linked with the same transmission chain as the existing local epidemics in other provinces. Moreover, epidemiological investigation showed that on January 2, case A had come into contact with her cousin and his family who returned from an affected area outside the province.Conclusions:Based on the gene sequencing results and epidemiological investigation, the COVID-19 outbreak in Anyang city, Henan Province was a local epidemic and the source of it was a college student who returned to Anyang city from other province on December 28, 2021. These infections were linked to the same transmission chain as the existing local infection in other provinces.

Analysis of risk factors and a predictive model of malnutrition in disabled stroke patients / 中华物理医学与康复杂志

Objective:To analyze the risk factors for malnutrition among disabled stroke survivors and devise a prediction model.Methods:A total of 373 disabled stroke survivors treated in the Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University in 2021 formed a control group ( n=102) and a malnutrition group ( n=271) according to their nutritional status. Univariate correlation analysis and multivariate logistic regression were used to analyze the risk factors for malnutrition and their predictive value. Results:Age, dysphagia, pulmonary infection, disability score and feeding style were found to be related significantly to the occurrence of malnutrition. Multivariate logistic regression confirmed that age, pulmonary infection, dysphagia, low total intake and a low Barthel index were useful predictors of malnutrition in such persons. Moreover, patients who had received nasogastric tube feeding were at much higher risk of malnutrition than those with intermittent oroesophageal tube feeding. The area under the receiver operating characteristics curve of the Barthel index combined with dysphagia to predict malnutrition was 0.84. The critical value was 0.67 with a sensitivity of 88% and a specificity of 72.5%.Conclusions:Age, pulmonary infection, dysphagia, feeding method, total intake and disability score are risk factors for malnutrition in disabled stroke survivors. The Barthel index combined with dysphagia has good predictive power for the occurrence of malnutrition in such persons.

Failed pyeloplasty in children: our experience and clinical characteristics / 中华泌尿外科杂志

Objective:To summarize the clinical characteristics、diagnosis and treatment experience of children with reobstruction after pyeloplasty.Methods:A retrospective analysis was conducted on patients admitted to the Department of Urology, Beijing Children's Hospital from January 2015 to April 2022. Due to the unrelieved hydronephroplasty after the primary pyeloplasty, the anterior and posterior diameter of the pelvis was larger than that before the primary operation. Intravenous pyelography and diuretic renal radionuclide scanning confirmed the diagnosis of ureteropelvic reobstruction. Or underwent reoperation after undergoing puncture angiography for reobstruction. Fifty-four children were included in the study, 47 males (87.03%) and 7 females (12.96%), with a median age of 51.67(21.30, 117.24)month, and, 38 cases (70.37%) on the left side and 16 cases (29.63%) on the right side. The primary operation was open pyeloplasty (POP) in 20 cases and laparoscopic pyeloplasty (PLP) in 34 cases. 45 patients underwent primary operation in our hospital, and 9 patients were referred from other hospitals after primary operation. The interval between reoperation and initial operation was 7.25(6.15, 15.40)month. There were 28 cases with clinical symptoms before operation, and 26 cases without symptoms but reobstruction on imaging. 21 cases presented with recurrent abdominal pain, nausea and vomiting, and 7 cases presented with recurrent fever and urinary tract infection. All 54 patients underwent re-pyeloplasty after definite diagnosis of re-obstruction. In order to further study the feasibility of RLP, patients in the two groups were divided into RLP and ROP groups according to different surgical procedures. In the RLP group, there were 8 males (72.72%) and 3 females (27.28%). The median age was 82.21(49.83, 114.05) months, and obstruction was located on the left side in 8 cases (72.72%) and the right side in 3 cases (27.28%). There were 3 cases (27.28%) with POP and 8 cases (72.72%) with PLP. The time between the second operation and the primary operation was 12.83 (6.34, 16.86) months. APD before operation was 5.18 (4.25, 6.14) cm. There were 43 cases in the ROP group, including 38 males (88.37%) and 5 females (12.63%). The median age was 52.32 (26.62, 77.35) months; Obstruction was located on the left side in 31 cases (72.09%) and the right side in 12 cases (27.91%). The primary operation was performed in 19 cases (44.19%) with POP and 24 cases (55.81%) with PLP. The time between the second operation and the primary operation was 10.02 (8.03, 15.51) months. Preoperative APD was 5.42 (5.14, 5.90) cm. The causes of obstruction were found in the second operation: there were 28 causes (51.85%) of scar hyperplastic anastomotic stenosis, 7 cases (12.96%) of residual ectopic vascular compression, 8 cases (14.81%) of high ureteral anastomosis, 7 cases (12.96%) of ureteral adhesion distortion, and 4 cases (7.41%) of other causes (1 case of medical glue shell compression, 1 case of luminal polypoid hyperplasia, and 2 cases of complete luminal occlusion). Operation time, postoperative complications, APD, APD improvement rate (PI-APD), renal parenchyma thickness (PT), anteroposterior pelvis diameter/renal parenchyma thickness (APD/PT) at 3 and 6 months after operation were compared between RLP and ROP groups.Results:In this study, 54 patients were followed up with an average follow-up time of (34.41±20.20)month. APD of 3 months after pyeloplasty was 3.29(3.03, 3.52) cm, which was statistically significant compared with 5.45(5.13, 5.77)cm before pyeloplasty ( P=0.02). APD/PT changed from preoperative 21.71(21.08, 31.77)to 5.40(4.79, 6.79)3 months after surgery, and the difference was statistically significant ( P=0.03). The APD improvement rate was 37%(33%, 42%) 3 months after surgery and 49%(44%, 54%) 6 months after surgery. Among the 54 patients, 3 had lumbago and fever after clamping the nephrostomy tube, and 3(5.55%) had sinus angiography indicating that obstruction still existed and required reoperation. Therefore, the success rate of repyeloplasty in this group was 94.45%. Comparing RLP group and ROP group, operation time in RLP group was longer than that in ROP group [169.13(113.45, 210.66)]min vs. 106.83(103.14, 155.32)min, P=0.02]. The length of hospitalization in RLP group was shorter than that in ROP group [7.45(5.62, 9.28)d vs.11.64(10.45, 15.66)d, P=0.03], and the difference was statistically significant. The improvement rate of APD 3 months after surgery was compared between the two groups [30.48%(19.81%, 41.16%) vs.39.96%(35.16%, 47.76%), P=0.15], and the improvement rate of APD 6 months after surgery was compared between the two groups [48.00%(27.19%, 48.81%) vs.52.27%(46.95%, 56.76%), P=0.05], there was no significant difference in the success rate of operation between the two groups (90.90% vs. 95.34%, P=0.63). Conclusions:The common cause of reobstruction after pyeloplasty is cicatricial adhesion stenosis. The operation is challenging, but repyeloplasty can effectively relieve the obstruction and the overall success rate is 94.45%. RLP is a safe and effective surgical method for the treatment of reobstruction, which can achieve comparable surgical results with ROP.

Research advances on the artificial intelligence-based imaging diagnosis of pediatric DDH / 中华骨科杂志

Developmental dysplasia of the hip (DDH) is a common skeletal malformation in children and the prominent cause of hip osteoarthritis and lower limb disability. The therapeutic difficulty and effect of DDH are closely related to an early and proper diagnosis. Hip ultrasonography and anteroposterior pelvic radiography are preferred depending on the presence of the secondary ossification center of the femoral head. Conventional diagnostic methods primarily relied on manual measurements and empirical judgments by clinicians, which were laborious and generally lacked reliability. The effective integration of medical imaging and artificial intelligence algorithms is expected to improve the diagnosis of pediatric DDH and enhance the efficiency of clinical diagnosis and treatment. Segmentation algorithms based on the extraction of local geometric features, 3D map search-based segmentation algorithms, and deep learning networks were utilized to assist in analyzing hip ultrasound images, calculating key dysplasia indicators, and diagnosing DDH in infants under 4-6 months. Computer-aided techniques, such as bone edge detection and template matching algorithms, deep transfer learning algorithms, and local-global feature mining convolutional neural networks were used to automatically identify bony landmarks on pelvic radiographs for measuring hip parameters and evaluating DDH in children over 4-6 months. However, there were several crucial problems in the clinical application of the artificial intelligence model for the auxiliary diagnosis of DDH due to technical limitations and insufficient understanding of researchers. This paper aims to review the progress of application in the medical artificial intelligence technology for the clinical auxiliary diagnosis of DDH. The author also provides references for future research for truly intelligent diagnostic tools.

Identification and expression analysis of flavonoid O-methyltransferases gene family in Artemisia argyi / 药学学报

italic>Artemisia argyi (A. argyi) is a Chinese herbal medicine in China. The main active components are volatile oils, flavonoids, and other compounds, which have various pharmacological activities. Methoxylated flavonoids are the main active ingredients in A. argyi. Flavonoid O-methyltransferase (FOMT) is a key enzyme in the O-methylation of flavonoids. In order to further understand the function and characteristics of FOMT proteins, this paper carried out the whole genome mining and identification of FOMT genes in A. argyi and performed phylogenetic, chromosomal localization, gene sequence characterization, subcellular localization prediction, protein structure, gene structure analysis, and expression pattern analysis. The results showed that a total of 83 FOMT genes were identified in the genome of A. argyi. The phylogenetic tree shows that FOMT genes are divided into two subgroups, CCoAOMT (caffeoyl CoA O-methyltransferase) subfamily (32 genes) and COMT (caffeic acid O-methyltransferase) subfamily (51 genes). Gene sequence analysis showed that the number of amino acids encoded by FOMT was 70-734 aa, the molecular weight was 25 296.55-34 241.3 Da, and the isoelectric point was 4.51-9.99. Compared with 32 members of the CCoAOMT subfamily, nearly 1/3 of the 51 members of the COMT subfamily were hydrophobic proteins and 2/3 were hydrophilic proteins. Subcellular localization prediction showed that more than 80% of CCoAOMT subfamily members were located in the cytoplasm, and 96% of COMT subfamily members were located in the chloroplast. COMT subfamily members have more motifs than CCoAOMT subfamily members. The N-terminal motifs of COMT subfamily proteins are relatively variable, while the C-terminal motifs are relatively conserved. Expression pattern analysis showed that CCoAOMT subfamily members were mainly expressed in roots, while COMT members were mainly expressed in leaves. Some FOMTs showed the tissue expression specificity by real-time quantitative PCR analysis, especially in leaves. In this study, we identified and analyzed the FOMT gene family in A. argyi, and provided a theoretical basis for further research on the function of FOMTs and the biosynthesis of methylated flavonoids in A. argyi.