Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells to Osimertinib by Regulating Methylation of DUSP1 / 中国肺癌杂志

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.

Efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in treatment of patients with genotype 3B HCV/HIV infection / 临床肝胆病杂志

ObjectiveTo investigate the efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in Chinese patients with genotype 3B HCV/HIV infection. MethodsA total of 299 patients with genotype 3B HCV/HIV infection who attended The Third People’s Hospital of Kunming from January 2017 to December 2020 were enrolled and treated with sofosbuvir/velpatasvir alone or in combination with ribavirin for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment （SVR12） and adverse reactions. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the Agresti-Coull method was used to evaluate the 95% confidence interval （CI） of SVR12； univariate and multivariate non-conditional logistic regression analyses were used to investigate the influencing factors for SVR. ResultsThe 299 patients with genotype 3B HCV/HIV infection had a mean age of 43.92±6.84 years， among whom the male patients accounted for 77.3% （231/299）， the patients with liver cirrhosis accounted for 36.5% （109/299）， the patients with a history of antiviral therapy accounted for 13.4% （40/299）， and the patients receiving sofosbuvir/velpatasvir combined with ribavirin accounted for 27.8% （83/299）. The overall SVR was 87.0% （260/299） for all patients， and there was no significant difference in SVR12 between the patients receiving sofosbuvir/velpatasvir alone and those receiving sofosbuvir/velpatasvir combined with ribavirin （87.5% vs 85.5%， χ2=0.203， P=0.653）. There was a significant difference in SVR12 between the patients without liver cirrhosis and those with liver cirrhosis （90.0% vs 81.7%， χ2=4.256， P=0.039）， and the patients receiving antiviral therapy for the first time had a significantly higher SVR12 than the treatment-experienced patients （93.4% vs 45.0%， χ2=71.670， P<0.001）. The univariate and multivariate logistic regression analyses showed that platelet count （odds ratio ［OR］=0.957， 95%CI： 0.931 — 0.984， P=0.002）， liver stiffness measurement （OR=1.446， 95%CI： 1.147 — 1.822， P=0.002）， and experience in treatment （OR=13.807， 95%CI： 2.970 — 64.174， P=0.001） were independent influencing factors for SVR in patients with genotype 3B HCV/HIV infection. There were 41 cases of serious adverse events， all of which occurred within 2 weeks after antiviral therapy， and 28 cases were resolved without drug withdrawal or active treatment， while 13 cases were not resolved after active treatment and were resolved after the antiviral drugs were stopped for 2‍ ‍—‍ ‍5 days， with no similar reactions observed when the drugs were used again after remission. ConclusionSofosbuvir/velpatasvir alone or in combination with ribavirin has relatively good efficacy and safety in patients with genotype 3B HCV/HIV infection.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P&#x0026;#x003C;0.001). Compared with the control group, the noDR group had significantly higher AVD(P&#x0026;#x003C;0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P&#x0026;#x003C;0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica / 解剖学报

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Impact of autonomic nerve function on motor function in patients with post-stroke depression / 中国康复理论与实践

ObjectiveTo explore the impact of autonomic nerve function on motor function in patients with post-stroke depression (PSD) from the perspective of regional homogeneity (ReHo). MethodsFrom January to December, 2020, a total of 60 inpatients and outpatients with cerebral infarction in the Affiliated Brain Hospital of Nanjing Medical University were divided into control group (n = 30) and PSD group (n = 30). Two groups were assessed using Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Heart rate variability (HRV) was measured. Ten patients in each group were selected randomly to undergo resting state functional magnetic resonance imaging (rs-fMRI) to calculate ReHo. ResultsAll HRV indices were lower in PSD group than in the control group (|t| > 2.092, P < 0.05). In PSD group, FMA and MBI scores showed positive correlations with 24-hour standard deviation of normal-to-normal R-R intervals (SDNN), the root mean square of successive differences between normal heartbeats over 24 hours (RMSSD), the percentage of differences between adjacent normal R-R intervals over 24 hours that were greater than 50 ms (PNN50), total power (TP), very low frequency power (VLF) and low frequency power (LF) (r > 0.394, P < 0.05), and showed negative correlations with HAMD scores (|r| > 0.919, P < 0.001). HAMD scores in PSD group were negatively correlated with SDNN, RMSSD, PNN50, TP and VLF (|r| > 0.769, P < 0.001). Compared with the control group, the ReHo increased in PSD group in the right rectus gyrus (142 voxels, t = 6.575), the left medial and paracingulate gyri (204 voxels, t = 4.925) (GRF correction, P-Voxel < 0.005，P-Cluster < 0.05); and reduced in the right cerebellum (191 voxels, t = -6.487), the left middle temporal gyrus (140 voxels, t = -5.516), and the left precentral gyrus (119 voxels, t = -4.764) (GRF correction, P-Voxel < 0.005，P-Cluster < 0.05) in PSD group. ConclusionAutonomic nerve function is related to motor dysfunction in patients with PSD. The modulation of emotional, cognitive and motor brain regions by the autonomic nervous system may play a role in influencing the motor function in patients with PSD.

Analysis of Chemical Components and Tissue Distribution of Lujiao Formula Based on UPLC-Q-Orbitrap-MS / 中国实验方剂学杂志

ObjectiveTo qualitatively analyze the chemical constituents and their tissue distribution in Lujiao formula based on ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）. MethodThe separation was performed on an ACQUITY UPLC® BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-methanol（B） in a gradient elution（0-2 min， 4%B； 2-6 min 4%-12%B； 6-38 min， 12%-70%B； 38-38.5 min， 70%B； 38.5-39 min， 70%-95%B； 39-43 min， 95%B； 43-43.1 min， 95%-4%B； 43.1-45 min， 4%B）， the flow rate was 0.3 mL·min-1 with the column temperature of 40 ℃ and the injection volume of 5 µL. The data were acquired by an electrospray ionization（ESI） in the full scanning mode of positive and negative ions， the scanning rang was set at m/z 100-1 500， the collision energies were 10， 20， 40 eV. Retention time， precise relative molecular mass and secondary mass spectrometry fragment ions were used to identify the compounds in Lujiao formula and analyze their tissue distribution， combing with self-established database and comparing with standard substances and published literature data. ResultA total of 260 compounds， including 156 flavonoids， 43 terpenoids， 18 coumarins， 13 organic acids， 7 phenylethanoids， 7 alkaloids and 16 others， were identified or hypothesized from Lujiao formula， 68 of which were identified by comparison with standard substances. And the results of tissue distribution showed that 100， 143， 129 and 126 prototype components were detected in blood， heart， liver and kidney， respectively. ConclusionThe chemical composition of Lujiao formula and their tissue distribution were systematic analyzed， which can provide reference for the quality control， clinical application， pharmacokinetics and pharmacodynamic material basis of Lujiao formula and its medicinal materials.

Historical Evolution and Key Information Research on Pediatric Famous Classical Formula Yigongsan / 中国实验方剂学杂志

Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The directionality of measurement bias: a directed acyclic graph-based structural perspective / 中华流行病学杂志

Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Differences in Contents and Formation Methods of Clinical Questions in Chinese and Korean Clinical Practice Guidelines of Acupuncture-Moxibustion: Scoping Review / 中国结合医学杂志

OBJECTIVE@#To analyze the differences in the needs of users and the value orientation of clinical practice guidelines (CPGs) by comparing the contents and formation methods of clinical questions in Chinese and Korean CPGs of acupuncture-moxibustion (Acup-Mox).@*METHODS@#The full text of CPGs was systematically searched from the official websites of Chinese and Korean traditional medicine societies and Acup-Mox associations, with the topic "Acup-Mox for treating diseases" and the retrieval time up to September 28, 2022. Two researchers screened the CPGs independently, and extracted the guidelines' topics, content, quantity and formation methods of clinical questions. The quantitative data were collected by counting the frequency, and the qualitative data were classified and described by thematic analysis.@*RESULTS@#A total of 29 guidelines were included in this study, including 20 Chinese guidelines (305 questions) and 9 Korean guidelines (223 questions). The differences lie in the aspects of content and diversity, and formation method. As for content and diversity, Chinese guidelines focused mainly on the questions related to treatment such as the operation of specific intervention (86, 28.2%), efficacy of intervention (78, 25.6%), and also involving questions in diagnosis, prevention, and prognosis. While the clinical questions in Korean guidelines were concentrated to efficacy of intervention (218, 97.8%). As for formation method, in Chinese guidelines, questions were usually collected directly from clinicians, and then determined and optimized by experts. In Korean guidelines, frequently used clinical Acup-Mox interventions would be screened first. Then the expert group would set up corresponding intervention control measures so as to form clinical questions related to treatment efficacy.@*CONCLUSIONS@#The differences reflect the different needs of clinical practitioners, and the different aims or concepts in developing Acup-Mox guidelines between China and South Korea. Chinese guidelines emphasized promoting operation protocols and techniques of Acup-Mox for practical use, while Korean guidelines emphasized promoting the frequently used clinical intervention therapies. It is speculated that the guidelines from these two countries would play different roles in guiding clinical operation and supporting medical decision. In terms of formation methods of clinical questions, it is suggested to attach importance to optimizing process in formatting clinical questions to improve the clinical applicability of CPGs of Acup-Mox.

Factors influencing the chronic post-surgical pain after laparoscopic surgery for elderly patients with urinary tract tumors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the incidence and potential influence factors that contribute to chronic post-surgical pain (CPSP) in elderly patients with urinary tract tumors who underwent laparoscopic procedures.@*METHODS@#A retrospective study was conducted to collect the clinical data of 182 elderly patients with urinary tract tumors who were ≥65 years and underwent laparoscopic surgery from October 2021 to March 2022 in Peking University Third Hospital. The patients'demographic information, medical history and the severity of postoperative pain were collected. Telephone follow-ups were made 6 months after surgery, and the patients' CPSP conditions were recorded. The diagnostic criteria of CPSP were referred to the definition made by the International Association for the Study of Pain (IASP): (1) Pain that developed or increased in intensity after surgical procedure and persisted for at least 3 months after surgery; (2) Pain that localized to the surgical field or projected to the innervation territory of a nerve situated around the surgical area; (3) Pain due to pre-existing pain conditions or infections and malignancy was excluded. The patients were divided into two groups based on CPSP diagnosis. Risk factors that predisposed the patients to CPSP were identified using univariate analysis. A multivariate Logistic regression model using back-forward method was designed, including both variables that significantly associated with CPSP in the univariate analysis (P < 0.1), and the variables that were considered to have significant clinical impact on the outcome.@*RESULTS@#Two hundred and sixteen patients with urinary tract tumors who had undergone laparoscopic surgery were included, of whom, 34 (15.7%) were excluded from the study. For the remaining 182 patients, the average age was (72.6±5.2) years, with 146 males and 36 females. The incidence of CPSP at the end of 6 months was 31.9% (58/182). Multiva-riate regression analysis revealed that age ≥75 years (OR=0.29, 95% CI: 0.12-0.73, P=0.008) was the protecting factors for postoperative chronic pain in the elderly patients with urinary tract tumors undergoing surgical treatment, while renal cancer (compared with other types of urinary tract tumors) (OR=3.68, 95% CI: 1.58-8.58, P=0.003), and the 24 h postoperative moderate to severe pain (OR=2.57, 95% CI: 1.14-5.83, P=0.024) were the independent risk factors affecting CPSP.@*CONCLUSION@#Age < 75 years, renal cancer and the 24 h postoperative moderate to severe pain are influence factors of the occurrence of CPSP after laparoscopic surgery in elderly patients with urinary tract tumors. Optimum postoperative multimodal analgesia strategies are suggested to prevent the occurrence of CPSP.

Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children.@*METHODS@#The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared.@*RESULTS@#A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011).@*CONCLUSIONS@#The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.

Association of gene polymorphisms of MyD88 and TICAM1 and their interactions with community-acquired pneumonia in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the association of single nucleotide polymorphisms (SNPs) of myeloid differentiation factor 88 (MyD88) and Toll-like receptor adaptor molecule 1 (TICAM1) and their interactions with community-acquired pneumonia (CAP) in children.@*METHODS@#Improved multiple ligase detection reaction assay was used for detecting the polymorphisms of nine tagging SNPs of the MyD88 and TICAM1 genes in 375 children with CAP who attended the Department of Pediatrics of the Second Affiliated Hospital of Yan'an University Medical School from August 2015 to September 2017 and 306 healthy children who underwent physical examination. A logistic regression analysis was used to evaluate the association between the distribution of genotypes and their interactions with CAP in children.@*RESULTS@#The polymorphism of the TICAM1 gene at rs11466711T/C locus was closely associated with the susceptibility to CAP in children (P<0.05). The AA genotype of rs35747610G/A locus significantly reduced risk of sepsis in children with CAP (P<0.05). The AA genotype of rs6510826G/A locus was significantly associated with the increase in C-reactive protein level in children with CAP (P<0.05). The GG genotype of the MyD88 gene at rs7744A/G locus significantly increased the risk of respiratory failure and circulatory failure (P<0.05). The multiplicative interactions between MyD88 gene rs7744A/G and TICAM1 gene rs11466711T/C, rs2292151G/A, rs35299700C/T, and rs35747610G/A loci were significantly associated with the susceptibility to CAP, the severity of CAP, and the risk of sepsis in children (P<0.05).@*CONCLUSIONS@#The gene polymorphisms of MyD88 and TICAM1 and their interactions are closely associated with CAP in children, with a synergistic effect on the development and progression of CAP in children.

Value of contrast-enhanced percutaneous ultrasound in the diagnosis of rotator cuff tear subtype / 中国骨伤

OBJECTIVE@#To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes.@*METHODS@#From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated.@*RESULTS@#The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears).@*CONCLUSION@#Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Combining transcranial magnetic stimulation with interactive virtual scenario training can improve the upper limb motor function of stroke survivors / 中华物理医学与康复杂志

Objective:To observe any effect of combining low-frequency transcranial magnetic stimulation (rTMS) with interactive virtual scenario training on the recovery of upper limb motor function after a stroke.Methods:Ninety stroke survivors were randomly divided into a pseudo-rTMS group, an rTMS group and a combination group, each of 30. In addition to basic medication, conventional rehabilitation and nursing care, the pseudo-rTMS, rTMS and combination groups received either sham rTMS treatment, 1Hz rTMS or virtual situational interaction along with 1Hz rTMS 5 days a week for 4 weeks. Before and after the 4 weeks their motor evoked potentials, cortical latency and central motor conduction time were measured, and surface electromyography was applied to the affected biceps brachii and triceps brachii. Meanwhile, the National Institutes of Health Stroke Scale, the Fugl-Meyer upper extremity assessment and the modified Barthel index were employed to assess the degree of neurological deficit, upper extremity motor function and ability in the activities of daily living (ADL).Results:After the 4-week intervention, a significant improvement was observed in all of the outcome measurements with all three groups. At that time the average scores of the rTMS group were significantly better than the pseudo-rTMS group′s averages but the average scores of the combination group were significantly better than those of either of the other two groups.Conclusion:Repeated application of low-frequency transcranial magnetic stimulation combined with virtual scenario interactive training can effectively improve the upper limb motor function and ADL performance of stroke survivors, and relieve the symptoms of neurological deficit. The combined therapy is worthy of application in clinical practice.

Surveys on management of neonatal respiratory distress syndrome in ten hospitals in Northwest China in 2016 and 2021 / 中华围产医学杂志

Objective:To analyze the status of neonatal respiratory distress syndrome (RDS) management in 10 hospitals in Northwest China over the past five years and to investigate the strategies for improving the prevention and treatment of RDS.Methods:This retrospective study involved premature infants with RDS who were admitted to the neonatal intensive care units (NICU) of 10 hospitals (six in Shaanxi Province, three in Gansu Province, and one in Xinjiang Uygur Autonomous Region) of the Northwest China Neonatal Collaborative Group within 3 d after birth from January 1 to December 31, 2016, and from January 1 to December 31, 2021. Basic information, perinatal condition, treatment approaches, complications, and prognosis of the patients were compared. T-test, rank sum, and Chi-square tests were used for statistical analysis. Result:(1) This study enrolled 322 premature infants with RDS in 2016 and 349 in 2021. Premature infants at the gestational age of 30 to 33 weeks were mainly affected, and the majority were male [64.3% (207/322) and 57.3% (200/349)]. The average maternal age in 2021 was older than that in 2016 [(30.6±4.8) years vs (28.6±5.4) years, t=24.02, P<0.001], and the proportion of women at advanced maternal age was also higher in 2021 [19.2% (67/349) vs 12.4% (40/322), χ2=4.18, P<0.05]. (2) The proportions of pregnancies conceived with assisted reproductive technologies [11.7% (41/349) vs 1.9% (6/322), χ2=25.12], underwent routine prenatal examinations [58.5% (204/349) vs 30.4% (98/322), χ2=53.33], exposed to steroids [62.2% (217/349) vs 28.6% (92/322), χ2=82.58] and delivered by cesarean section or elective cesarean section [73.6% (257/349) vs 51.6% (166/322), χ2=35.06; 24.1% (84/349) vs 6.5% (21/322), χ2=39.07], as well as the ratio of cesarean scar pregnancy [7.4% (26/349) vs 3.4% (11/322), χ2=5.23] were all higher in 2021 than those in 2016 (all P<0.05). Moreover, the incidence of fetal distress [30.1% (105/349) vs 20.2% (65/322), χ2=8.68], gestational hypertension [24.6% (86/349) vs 13.0% (42/322), χ2=14.59], premature rupture of membranes [16.0% (56/349) vs 10.2% (33/322), χ2=4.89], meconium-stained amniotic fluid [12.6% (44/349) vs 5.6% (18/322), χ2=9.83], placental abruption [10.3% (36/349) vs 5.3% (17/322), χ2=5.84], gestational diabetes mellitus [10.3% (36/349) vs 1.6%(5/322), χ2=22.41], chorioamnionitis [4.6%(16/349) vs 0.9% (3/322), χ2=8.12], thyroid dysfunction [4.3% (15/349) vs 0.6% (2/322), χ2=7.88] and heart disease [4.3% (15/349) vs 0.3% (1/322), χ2=9.17] were higher in 2021 than in 2016 (all P<0.05). (3) In 2021, the rate of pulmonary surfactant (PS) usage, the dosage of porcine PS, and the proportion of bovine PS usage were all significantly higher than those in 2016 [73.6% (257/349) vs 67.1% (216/322), χ2=11.62; (178.5±38.0) mg/kg vs (165.2±42.8) mg/kg, t=7.85; 47.9% (123/257) vs 19.4% (42/216), χ2=41.72; all P<0.01]. No significant difference in the incidence of intubation-surfactant-extubation (INSURE), early PS administration (≤2 h after birth), or the arterial blood gas values before and after PS treatment was found between the cases enrolled in 2021 and 2016. The duration of antibiotic treatment [7.0 d (5.0-14.0 d) vs 5.0 d (1.0-8.0 d), Z=7.55] and assisted ventilation [144 h (81-264 h) vs 73 h (47-134 h), Z=8.20] and the median hospital stay [24 d(14-42 d) vs 16 d (10-25 d), Z=6.74] were significantly longer in 2021 than in 2016 (all P<0.01). More patients required nasal intermittent positive pressure ventilation [29.6% (100/338) vs 1.0% (3/306), χ2=97.81] and conventional ventilation [42.6% (144/338) vs 30.1% (92/306), χ2=10.87] in 2021 as compared with those five years ago (both P<0.01). (4) In 2021, the incidence of patent ductus arteriosus [15.5% (54/349) vs 6.2% (20/322), χ2=63.40], bronchopulmonary dysplasia [9.2% (32/349) vs 2.8% (9/322), χ2=12.88], persistent pulmonary hypertension [5.4% (19/349) vs 0.6% (2/322), χ2=12.85], periventricular leukomalacia [4.3% (15/349) vs 1.2% (4/322), χ2=7.52] and pneumothorax [3.4% (12/349) vs 0.3% (1/322), χ2=9.68] increased as compared with those in 2016 (all P<0.05), while the incidence of nosocomial infection decreased significantly [7.4% (26/349) vs 19.6% (63/322), χ2=21.37, P<0.001]. (5) The cure rate of premature infants with RDS was 70.8% (247/349) in 2021, which was significantly higher than that in 2016 [56.2% (181/322), χ2=15.37, P<0.001]. Moreover, the rate of withdrawing treatment and the total mortality rate was lower in 2021 than in 2016 [7.7% (27/349) vs 14.3% (46/322), χ2=7.41; in-hospital: 1.4% (5/349) vs 5.6% (18/322), χ2=8.74; out of hospital: 8.3% (29/349) vs 13.7% (44/322), χ2=4.96; all P<0.05]. Conclusions:The clinical management of RDS in premature infants in the involved hospitals has been improved. However, there is room for improvement in prenatal examinations.

A case report of mitochondrial enoyl-CoA hydratase short chain 1 deficiency caused by enoyl-CoA hydratase short chain 1 gene mutation / 中华神经科杂志

Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.

Da-vinci robot-assisted surgery vs laparoscopic repair for the treatment of hiatal hernia repair / 中华普通外科杂志

Objective:To compare Da-vinci robotic surgical system with laparoscopic surgery for the repair of hiatal hernia.Methods:The clinical data of 115 patients undergoing minimally invasive Nissen fundoplication at the Department of Hernia and Abdominal Wall Surgery, the Affiliated Hospital,Xuzhou Medical University from Dec 2019 to May 2022 were retrospectively studied. After propensity score matching (PSM), 46 cases in each group were included:Robot-assisted surgery (RS group) and laparoscopic surgery (LS group). Postoperative complications were collected and GERD Questionnaire (GERDQ) were used as the standard in evaluation of the results.Results:Patients in RS group had less intraoperative bleeding ( P<0.001), shorter postoperative gastrointestinal recovery time ( P<0.001), and shorter postoperative hospital stay ( P=0.002). The LS group had a shorter operative time ( P<0.001) and lower total hospital cost ( P<0.001). GERD-Q scores decreased significantly in both groups at 3 and 6 months postoperatively compared with preoperative scores ( P<0.001). There was no statistically significant difference between the two groups in the incidence of postoperative complications ( P>0.05). No recurrence was seen in both groups during postoperative follow-up. Conclusion:Da-vinci robot-assisted repair of hiatal hernia is as safe and feasible as laparoscopic procedures, with less intraoperative trauma and quicker, earlier recovery.