Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Small incision lenticule extraction for the treatment of myopic anisometropia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the clinical effect of small incision lenticule extraction(SMILE)on the treatment of myopic anisometropia.METHODS: Clinical data of 76 patients(146 eyes)with myopic anisometropia who received SMILE or femtosecond assisted laser in situ keratomileusis(FS-LASIK)in our hospital from January 2021 to December 2022 were retrospectively analyzed. The patients were divided into SMILE group(39 cases, 77 eyes)and FS-LASIK group(37 cases, 69 eyes)according to surgical methods. Uncorrected visual acuity(UCVA), diopter, anisometropia, corneal aberration and occurrence of postoperative complications were compared between the two groups at 1 wk, 1 and 3 mo after surgery.RESULTS: The UCVA of the two groups was improved after surgery compared with that before surgery, and the coma, trefoil, spherical aberration and total higher-order aberration were significantly increased compared to those before surgery(P<0.05), and the coma, trefoil, spherical aberration and total higher-order aberration in the FS-LASIK group were significantly higher than those in the SMILE group(P<0.05). After follow-up to 3 mo after surgery, the incidence of postoperative complications was significantly lower in the SMILE group than that in the FS-LASIK group(5.2% vs 15.9%, P<0.05).CONCLUSION: Both SMILE and FS-LASIK can effectively enhance the UCVA and improve the visual quality in patients with myopic anisometropia, but SMILE has lower corneal higher order aberrations, lower incidence of postoperative complications and better overall effect.

The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

Study of prefrontal cortex activation characteristics of patients with psychiatric disorders in verbal fluency task using functional near-infrared spectroscopy / 四川精神卫生

BackgroundFunctional near-infrared spectroscopy （fNIRS） is a new generation of imaging tool that can be used to assist the diagnosis of psychiatric disorders. However， whether the patterns of prefrontal cortex activation observed by fNIRS are specific for different psychiatric disorders remains to be explored. ObjectiveTo investigate the characteristics of prefrontal cortex activation in patients with depression， anxiety disorder， bipolar disorder and schizophrenia in verbal fluency task （VFT） using fNIRS. MethodsFrom September to December 2021， 39 patients with schizophrenia， 205 patients with depressive disorder， 212 patients with anxiety disorder and 77 patients with bipolar disorder meeting the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited in the outpatient and inpatient department of West China Hospital， Sichuan University. fNIRS was used to monitor the prefrontal cortex hemodynamic changes of patients under VFT， and the clinical symptoms of patients were assessed by Symptom Checklist 90 （SCL-90） and Hypomania Checklist-32 items（HCL-32）. Differences in mean oxyhemoglobin （HbO2） concentration and the initial slope from 2 to 7 second during VFT were compared among patients with different diseases， and the correlation between mean HbO2 concentration/initial slope and clinical symptoms was analyzed by partial correlation analysis. ResultsThe concentration of HbO2 in channel 4 （Z=2.828， P=0.028） and channel 6 （Z=2.912， P=0.022） in patients with depression were significantly higher than those in patients with schizophrenia. Patients with anxiety had significantly higher changes in mean HbO2 concentration in channel 4 （Z=3.154， P=0.010）， channel 5 （Z=3.021， P=0.015）， channel 6 （Z=2.980， P=0.017） and of all channels （Z=2.881， P=0.024） than those of schizophrenia patients. There was a statistically significant difference in the initial slope of channel 3 between patients with depressive disorder and those with bipolar disorder （Z=2.691， P=0.039）. Among patients with bipolar disorder， the anger-hostility scores of SCL-90 were negatively correlated with the mean HbO2 concentration changes in channel 4 （r=-0.505， P=0.004）， channel 6 （r=-0.390， P=0.004）， channel 15 （r=-0.546， P=0.002）， channel 16 （r=-0.550， P=0.002） and the mean HbO2 concentration changes of all channels （r=-0.491， P=0.006）. ConclusionPatients with schizophrenia had lower activation in frontopolar and orbitofrontal region than patients with depression and anxiety disorder， and the initial slope of the right frontopolar， inferior frontal and orbitofrontal region in patients with depression is higher than patients with bipolar disorder. In addition， patients with bipolar disorder had less activation in the frontopolar and orbitofrontal lobe， the insular cover of Broca's area and the upper outer frontal cortex， and were more irritable and hostile. ［Funded by 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project， West China Hospital， Sichuan University （number， ZYJC21083）］

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Diagnosis and treatment of four cases of asymptomatic and non-hydrous ureteral calculi / 北京大学学报(医学版)

This paper analyzed the clinical data, diagnosis and treatment of 4 asymptomatic patients with ureteral calculi without hydrops in our hospital from October 2018 to January 2019, and comprehensively discussed the previous literature. The 4 patients in this group had no obvious clinical symptoms, no positive stones were found in the B-ultrasound of the urinary system, and no hydroureter and hydroureter of the affected side was found. Urinary CT scan confirmed ureteral stones. They were all located in the lower ureter, and the stones obstructed the lumen. The stones were round and smooth, and there was no obvious hyperplasia and edema in the surrounding mucosa. The lithotripsy was completed in the first-stage operation, and the DJ catheter was left behind for one month after the operation. Based on the clinical diagnosis and treatment process of the 4 cases of asymptomatic calculi in this group and the analysis of previous studies, these patients were mostly detected by imaging examinations or other systematic imaging examinations during the regular review of urinary calculi. Ureteral stones with obstruction did not necessarily have stone-related symptoms. The onset of renal colic involved an increase in intraluminal pressure, related stimulation of nerve endings, smooth muscle spasms caused by stretching of the ureteral wall, and systemic changes in cytokines and related hormones. Cascade reactions, etc., were associated with the movement of stones down. Ureteral stones without hydrops were mostly located in the lower ureter, which had a certain buffering effect on obstructive pressure. Asymptomatic ureteral calculi could also induce irreversible damage to renal function, and the proportion of damage increased with the diameter of the stone. Patients with a history of urinary calculi, especially those with asymptomatic stones for the first time, should be paid attention to during clinical follow-up. At present, there are few research reports on asymptomatic and non-accumulating ureteral calculi. We analyze the clinical diagnosis and treatment process and characteristics of this group of patients combined with previous literature to provide a reference for the diagnosis and treatment of such patients.

Association of Serine/Threonine Phosphoprotein Phosphatase 4C Expression With Prognosis of Gastric Cancer / 中国医学科学院学报

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.

Characteristics of vaginal microbiota in pregnant women with premature rupture of membranes and establishment of prediction model / 中华微生物学和免疫学杂志

Objective:To study the characteristics of vaginal microbiota in pregnant women with premature rupture of membranes (PROM) and to establish prediction models for PROM.Methods:This study involved 35 women with preterm premature rupture of membranes (PPROM), 180 with term premature rupture of membranes (TPROM) and 255 term birth cases without premature rupture of membranes (TBWPROM, control group). The V3-V4 hypervariable region sequences in the vaginal samples collected at 16-28 weeks of gestation were detected by 16S rRNA gene next-generation sequencing. The differences in Alpha and Beta diversity, and the attributes and metabolic function prediction of each recognized species among the three groups were analyzed. Subsequently, a random forest model was used to establish the prediction models for PROM using vaginal microbiota species and environmental risk factors.Results:Compared with the control group, the Alpha diversity of the PPROM group was higher (Observed features, P=0.022; Faith_pd index, P=0.024) and Beta diversity was also significantly different (Unweighted UniFrac, P=0.010; Jaccard index, P=0.008). In PPROM cases, Megasphaera genomosp. typeⅠ was significantly increased ( P=0.017) and Lactobacillus mulieris was significantly decreased ( P=0.003). In the patients with TPROM, Megasphaera was significantly increased ( P=0.009) and Lactobacillus mulieris was significantly decreased ( P=0.002). In terms of functional pathways, sulfur oxidation ( P=0.021), methanogenesis from acetate ( P=0.036), L-histidine biosynthesis ( P=0.009), adenosylcobalamin biosynthesis ( P=0.041) and fucose degradation ( P=0.001) were significantly increased in patients with PPROM; L-histidine biosynthesis ( P<0.001) and fucose degradation ( P=0.030) were significantly increased in patients with TPROM. The prediction models were established using the random forest model with vaginal microbiota species and environmental risk factors and the prediction model for PPROM performed well [AUC: 0.739 (95%CI: 0.609-0.869), sensitivity: 0.928, specificity: 0.659, positive predictive value: 0.750, negative predictive value: 0.906], which had a certain reference value. Conclusions:Vaginal microbiota might be related to the development and progression of PROM. Studying the differences in vaginal microbiota might provide a new idea for the prevention and treatment of PROM. Functional prediction provided a direction for further research on the mechanism of PROM. The established prediction model could prevent the occurrence of PPROM and promote maternal and infant health.

Role of S1PR1 in dorsal root ganglion in remifentanil-induced hyperalgesia in rats with incisional pain / 中华麻醉学杂志

Objective:To evaluate the role of sphingosine-1-phospho-1 receptor(S1PR1)in the dorsal root ganglion in remifentanil-induced hyperalgesia in rats with incisional pain.Methods:Forty-eight male Sprague-Dawley rats with successful intrathecal and caudal vein catheterization, weighing 260-280 g, aged 2-3 months, were divided into 6 groups ( n= 8 each) using a random number table method: control group (group C), S1PR1 antagonist (FTY720) group (group F), remifentanil group (group R), remifentanil + S1PR1 antagonist (FTY720) group (group R+ F), remifentanil + incisional pain group (group R+ I), and remifentanil + incisional pain + S1PR1 antagonist (FTY720) group (group R+ I+ F). In C group, normal saline 0.1 μg·kg -1·min -1 was intravenously infused for 60 min. In R group, remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein. In F group, FTY720 3 nmol was intrathecally injected, and 10 min later normal saline 1.0 μg· kg -1·min -1 was infused for 60 min via the caudal vein. In R+ F group, FTY720 3 nmol was intrathecally injected, and 10 min later remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein. In R+ I group, remifentanil 1.0 μg·kg -1·min -1 was infused for 60 min through the caudal vein while the model of incisional pain was developed. In R+ I+ F group, FTY720 3 nmol was intrathecally injected, 10 min later the incisional pain model was prepared, and remifentanil 1.0 μg·kg -1·min -1 was injected for 60 min through the caudal vein at the same time. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before remifentanil or normal saline infusion (T 0) and 2, 6, 24 and 48 h after stopping remifentanil or normal saline infusion (T 1-4). Rats were sacrificed after the last measurement of pain threshold, and the L 4-6 segments of dorsal root ganglion were taken for determination of the expression of S1PR1, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), interleukin-1β (IL-1β) and glutamate transporter-1 (GLT-1) protein and mRNA (by Western blot and quantitative polymerase chain reaction). Results:Compared with C group, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in dorsal root ganglion was up-regulated, and the expression of GLT-1 protein and mRNA in dorsal root ganglion was down-regulated in R group ( P<0.05), and no significant change was found in the parameters mentioned above in group F ( P>0.05). Compared with R group, MWT was significantly decreased and TWL was shortened at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in dorsal root ganglion was up-regulated, and GLT-1 protein and mRNA expression in dorsal root ganglion was down-regulated in R+ I group, and MWT was significantly increased and TWL was prolonged at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in the dorsal root ganglion was down-regulated, and GLT-1 protein and mRNA expression in the dorsal root ganglion was up-regulated in R+ F group ( P<0.05). Compared with R+ I group, MWT was significantly increased and TWL was prolonged at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in the dorsal root ganglion was down-regulated, and the expression of GLT-1 protein and mRNA in the dorsal root ganglion was up-regulated in R+ I+ F group( P<0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia is associated with up-regulation of S1PR1 expression, activation of inflammatory factors, and down-regulation of GLT-1 expression in the rats with incisional pain.

Association of bone lesions distribution with prognosis in renal cell carcinoma bone metastasis / 中华泌尿外科杂志

Objective:To investigate the association between bone lesions distribution and survival outcome and prognostic risk stratification in renal cell carcinoma bone metastasis (RCC-BM).Methods:The data of 122 RCC-BM patients admitted to Peking University People's Hospital between January 2009 and December 2019 were retrospectively reviewed. There were 100 males and 22 females, with a baseline age of (59.87±11.33) years old. According to the Memorial Sloan-Kettering Cancer Center (MSKCC)/Motzer score, patients were stratified into different risk groups using profiles at first bone metastasis diagnosis, with 20 (16.4%), 74 (60.6%) and 28 (23.0%) patients in favorable, intermediate and poor group, respectively. The spatial distribution of bone metastasis was investigated at the first bone metastasis diagnosis. The overall distribution patterns were as follows: locoregional group (lesions only involved thoracic and/or lumbar vertebrates) in 26 cases (21.3%), stochastic group (bone lesions randomly distributed) in 69 cases (56.6%), extensive group (with concomitant visceral metastasis) in 27 cases (22.1%). Metastatic site involvement was as follows: spine in 48 cases(39.3%), pelvis in 43 cases (35.2%), upper extremities in 22 cases (18.0%), and lower extremities in 20 cases (16.4%). Half (61 cases) of the enrolled patients had synchronous bone metastasis as their first bone metastases were diagnosed simultaneously with their renal tumors. Of all the patients, 99 (81.1%) accepted radical nephrectomy, 6 (4.9%) accepted partial nephrectomy, and the other 17 patients (13.9%) accepted the treatment of ablation or embolization. Eighty-two patients (67.2%) received definitive treatment for bone metastatic lesions, respectively. Forty patients (32.8%) accepted the palliative tumor reduction therapy. Thirty-two patients (26.2%) received tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) medication, and 12 patients (9.8%) received local radiotherapy. Distribution variation and therapeutic strategies throughout the disease course until the last follow-up were recorded. Univariate analysis (chi-squared test, Mantel-Haenszel test), Kaplan-Meier survival analysis, and multivariate ordinal logistic regression were performed for the possible association.Results:Patients from the locoregional group (30.8%, 8/26) were prone to have higher risk stratification at first diagnosis than patients in the stochastic and extensive groups ( 20.8%, 20/96, P=0.107) as the marginal difference was found. At first bone metastasis diagnosis, RCC-BM patients with spinal involvement were more likely to have higher MSKCC risk stratification than those without spinal involvement [20.3%(15/48) vs. 17.6%(13/74), P<0.05]. Multivariate ordinal logistic regression showed that after adjusting for general data, bone metastasis sites, and concomitant visceral metastasis, RCC-BM patients with spinal involvement at first bone metastasis diagnosis were 3.3 times (95% CI 1.195-9.091, P<0.05)more likely to fall into the higher MSKCC risk group than those without spinal involvement.In those 93 cases with follow-up records, 20 (21.5%), 53 (57.0%), and 20 (21.5%) cases were in the locoregional group, stochastic group, and extensive group, respectively. The median overall survival time (mOS) of patients with pelvic involvement (36 cases) throughout the disease course was 32.0 months (95% CI 6.0-58.0), which was shorter than that of patients without pelvic involvement (57 cases, mOS 49.0 months, 95% CI 20.4-77.5, P<0.05). Conclusions:Spinal involvement (especially limited to thoracic and/or lumbar vertebrates) at first bone metastasis diagnosis and pelvic involvement throughout the disease course were associated with poor prognosis.

"Shapeshifter of the mycobacterial world" : Discuss the mechanism of morphological transformation of Mycobacterium abscesses / 中华临床感染病杂志

Mycobacterium abscessesus (MAB) is the most common species of rapidly growing pathogenic nontuberculous mycobacteria (NTM). MAB is also an opportunistic pathogen with high drug resistance. The unique structure of cell wall enables it to exist in different forms and to undergo morphological transformation, making it the "shapeshifter of the mycobacterial world" , which facilitates its survival in natural environment in a saprophytic manner; and also facilitates its invasion into the host with long-term survival and being pathogenic. This article reviews research progress on the specific deformability of MAB and the mechanism associated with its phenotypic transformation; discusses the evolutionary characteristics of MAB to adapt environmental changes to provide reference for better understanding the biological characteristics and pathogenicity of MAB.

Application of Mini-Clinical Evaluation Exercise combined with direct observation of procedural skills in standardized training of emergency medicine guided by professional physician qualification examination / 中华医学教育探索杂志

Objective:To investigate the application effect of Mini-Clinical Evaluation Exercise (Mini-CEX) combined with direct observation of procedural skills (DOPS) in standardized training of emergency medicine guided by professional physician qualification examination.Methods:Based on the time of emergency medicine teaching reform in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, 32 standardized training residents in Emergency Department before September 2020 were included as control group and were given traditional teaching, and 32 standardized training residents after September 2020 were included as observation group and were given Mini-CEX combined with DOPS teaching under the guidance of professional physician qualification examination. The two groups were compared in terms of Mini-CEX score, DOPS score, assessment score of comprehensive emergency skills, pass rate of professional physician qualification examination, and comprehensive teaching quality. SPSS 25.00 was used to perform the t-test and the chi-square test. Results:Compared with the control group after training, the observation group had significantly higher scores of Mini-CEX, DOPS, and comprehensive emergency skill assessment ( P<0.05). There were no significant differences between the two groups in the pass rates of theoretical and practical examinations in professional physician qualification examination, and the observation group had a significantly higher total pass rate than the control group ( P<0.05). The observation group had significantly higher comprehensive teaching quality scores than the control group ( P<0.05). Conclusion:Mini-CEX combined with DOPS guided by professional physician qualification examination can help to improve the teaching effectiveness of standardized training residents in emergency, enhance their comprehensive skills and emergency professional skills, achieve a relatively high pass rate of professional physician qualification examination, and improve their post competency, and thus it holds promise for clinical application.

Analysis of biochemical and genetic screening results for neonatal methylmalonic acidemia / 中华实用儿科临床杂志

Objective:To investigate the incidence rate and gene variation of methylmalonic academia (MMA) in Ji′nan city by analyzing biochemical and genetic screening results, and to explore the carrier frequency of MMA-related pathogenic genes in the population in Ji′nan.Methods:The children diagnosed with MMA by tandem mass spectrometry screening in Ji′nan Neonatal Disease Screening Centre from May 2011 to May 2022 were enrolled in this study.Their genetic test results were retrospectively analyzed and summarized.The dried heel blood tablets collected from 6 800 newborns were tested for neonatal gene screening. MMAA, MMAB, MMACHC and MMUT genes in 4 800 cases were detected by high-throughput sequencing+ target area capture technology.Ultra-multiplex polymerase chain reaction+ target gene locus capture technology was used to detect 174 target loci of 8 genes related to MMA in 2 000 cases.The hotspot mutation and related gene carrier rate of MMA were analyzed. Results:A total of 367 452 newborns were screened by tandem mass spectrometry, and 103 cases (56 males and 47 females) were diagnosed with MMA by screening.The estimated incidence of MMA was 1∶3 567.Among the 103 MMA cases, 76 were genetically diagnosed, and 4 gene variants of MMA ( MMAHC, MMUT, MMAA, MMADHC) were identified.A total of 6 800 neonates underwent neonatal genetic screening.Three of them were diagnosed with MMA.About 318 infants carried pathogenic variants of MMA, with a total carrier rate of 4.68%.Specifically, the carrier rates of MMACHC and MMUT gene variants were 3.09%(210/6 800) and 1.43% (97/6 800), respectively. Conclusions:MMA is the most common organic acid metabolism disorder in our country.The incidence and carrier rate of this disease are high in Jinan city.Neonatal genetic screening is an important supplement to neonatal biochemical screening.Carrier screening for MMA-related pathogenic genes is recommended for couples of childbearing age in Jinan.

Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats / 中医杂志

ObjectiveTo investigate the possible mechanism of Fugan Huaxian Decoction （扶肝化纤汤， FHD） against hepatic fibrosis （HF） from the perspective of immunity. MethodsForty-eight SD rats were randomly divided into blank group， model group， colchicine group， FHD high-， medium- and low-dose group， with eight rats in each group. Except for the blank group， the disease-syndrome combined model of HF with healthy qi deficiency and toxin accumulation pattern was established during six weeks in the other five groups. After successful modeling， the high-， medium- and low-dose FHD groups were respectively given 37.5， 18.75 and 9.38 g/（kg·d） of FHD granules by gavage， while the colchicine group received 2 mg/ （kg·d） of colchicine tablets by gavage， and the blank group and the model group were given 10 ml/（kg·d） of purified water， all for 3 weeks. The general condition of the rats was recorded. After the treatment， the histopathological morphology of the liver was observed by HE staining， and the levels of interleukin 10 （IL-10） and interleukin 17 （IL-17） in serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of helper T cells 17 （Th17） and regulatory T cells （Treg） in peripheral blood were detected by flow cytometry， and the Th17/Treg value was calculated. The mRNA expression of retinoic acid-related nuclear orphan receptor γ （RORγt） and fork-head/wing-like helix transcription factor （FoxP3） in liver tissue were detected by qRT-PCR. ResultsCompared to the general condition of rats in the blank group， those in the model group were listless， less active， stretched and pushed， arched and prone， having no resistance to gavage， significantly reduced food intake， loose stools， dirty anus， slow weight gain， dry and dull hair， purple and darkening skin of the limbs with ecchymoses， purple and black spots with varying degrees of the skin of the tail； hepatic fibrosis and hyperplasia of rats in model group were more obvious； serum IL-17， peripheral blood Th17 expression and Th17/Treg value， RORγt mRNA expression in the liver tissue significantly increased in the model group， while expression of IL-10， Treg and FoxP3 mRNA significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the general condition of the rats and the liver fibrosis of HE stained liver tissue were improved in all the medication groups； the expression of IL-17 and Th17， Th17/Treg， and RORγt mRNA expression significantly decreased， while expression of IL-10， Treg， and FoxP3 mRNA increased in the high- and medium-dose FHD groups and the colchicine group； the expression of IL-17， Th17， and RORγt mRNA decreased， while the expression of IL-10 and FoxP3 mRNA increased in the low-dose FHD group （P＜0.05 or P＜0.01）. And more improvements were found in the FHD high-dose group than FHD medium- and low-dose groups and colchicine group （P＜0.05 or P＜0.01）. ConclusionFHD can may regulate immune balance and act against fibrosis by regulating the expression of specific transcription factors FoxP3 and RORγt， affecting the differentiation of Th17 and Treg cells and Th17/Treg balance， and regulating the secretion of IL-10 and IL-17.

Needle retaining after electroacupuncture combined with cognitive training for post-stroke cognitive impairment: a multi-center randomized controlled trial / 中国针灸

OBJECTIVES@#To compare the efficacy of needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training in the treatment of post-stroke cognitive impairment (PSCI).@*METHODS@#A total of 206 patients with PSCI were randomized into a needle retaining group (103 cases, 9 cases dropped out) and an electroacupuncture group (103 cases, 6 cases dropped out). In addition to the conventional basic medical treatment and the rehabilitation treatment, in the needle retaining group, electroacupuncture at Shenting (GV 24) and Baihui (GV 20) was applied, with continuous wave of 50 Hz in the first 15 min and with disperse-dense wave of 2 Hz/50 Hz in the last 15 min, the needles were continuously retained for 1 h after electroacupuncture, during which cognitive training was adopted; in the electroacupuncture group, cognitive training was performed after the same electric stimulation exerted for 30 min, without additional needles retaining. The treatment was given once a day, 5 times a week for totally 8 weeks in the two groups. Before and after 8-week treatment, the TCM syndrome score was observed; before and after 4,8-week treatment, the scores of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and ability of daily living were observed in the two groups. The clinical efficacy of the two groups was evaluated after 8-week treatment.@*RESULTS@#After 8-week treatment, the TCM syndrome scores were increased compared with those before treatment in both groups (P<0.05); the TCM syndrome score in the needle retaining group was higher than that in the electroacupuncture group (P<0.05).After 4,8-week treatment, the scores of MMSE, MoCA and ability of daily living were increased compared with those before treatment in both groups (P<0.05); MMSE, MoCA scores after 4,8-week treatment and ability of daily living score after 8-week treatment in the needle retaining group were higher than those in the electroacupuncture group (P<0.05). The total effective rate was 90.4% (85/94) in the needle retaining group, which was superior to 82.5% (80/97) in the electroacupuncture group (P<0.05).@*CONCLUSIONS@#Both needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training can effectively treat PSCI, improve the clinical symptom, cognitive function and ability of daily living in PSCI patients. Needle retaining after electroacupuncture combined with cognitive training has a better therapeutic effect.

Occupational Burnout and Turnover Intention of Social Workers under the Context of Epidemic Prevention and Control: The Moderating Effect of Professional Self-care / 中国医学伦理学

To understand the current situation of occupational burnout, turnover intention, and professional self-care among social workers under the context of epidemic prevention and control, and the role of professional self-care in the relationship between occupational burnout and turnover intention, this study investigated 1 066 social workers in Fujian Province with Professional Self-Care Practice Scale, and the Burnout Scale. SPSS 26.0 and its PROCESS plug-in analysis were used, the results showed that the proportion of social workers with moderate and severe occupational burnout accounted for 44.22% and 29.99% respectively, the proportion with turnover intention in the past year accounted for 25.67%, and the average score of professional self-care was (22.57±5.98) points. There was a significant positive correlation between occupational burnout and turnover intention (r=0.29, P<0.01). Professional self-care of social workers was significant negatively correlated with occupational burnout (r=-0.46, P<0.01) and turnover intention (r=-0.16, P<0.01). Professional self-care played a moderating role in the relationship between occupational burnout and turnover intention (β=-0.01, P<0.05). This paper indicated that social workers had a high degree of occupational burnout and turnover intention, low level of professional self-care under the context of epidemic prevention and control, and the attention should be paid to the protective role of professional self-care.

Computer Vision in Medical Imaging and its Impact on the Rare Musculoskeletal Diseases / 罕见病研究

There are over 6000 rare diseases in the world, affecting more than 300 million people. Early and precise diagnosis of rare diseases has always been the goal in clinical medicine. Emerging computer vision technology now greatly enhance medicine and healthcare and shows the potential in assisting the diagnosis and treatment for rare diseases. The technology can be a useful tool for extracting disease-relevant patterns from medical imaging. However, the effectiveness of its application depends on the complexity of the medical cases. In this paper, we summarize the challenges and emerging solution for the application of computer vision in diagnosis, rehabilitation as well as management of rare musculoskeletal diseases.

Establishment and evaluation of predictive models of platelet transfusion effect in multi-center tumor patients / 中国输血杂志

【Objective】 To study the platelet transfusion predictive models in tumor patients and evaluate its application effect. 【Methods】 A retrospective study was conducted on 944 tumor patients, including 533 males and 411 females who received platelet transfusion in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, the Affiliated Cancer Hospital of Xinjiang Medical University and Kailuan General Hospital from August 2022 to January 2023. Multivariate Logistic regression analysis was used to establish the platelet transfusion predictive models, and Medcalc15.8 software was used to draw the receiver operating curve (ROC) to evaluate the application effect of the prediction model. The actual application effect of models was verified through 162 female clinical cases and 172 male clinical cases. 【Results】 The incidence of platelet transfusion refractoriness in tumor patients was 28.9% (273/944), with 33.2% (177/533) in males, significantly higher than that in females [23.4% (96/411)] (P<0.05). Platelet transfusion predictive models: Y1 (female) =-8.546+ (0.581×number of pregnancies) + (0.964×number of inpatient transfusion bags) + number of previous platelet transfusion bags (5-9 bags: 1.259, ≥20 bags: 1.959) + clinical diagnosis (lymphoma: 2.562, leukemia: 3.214); Y2 (male) =-7.600+ (1.150×inpatient transfusion bags) + previous platelet transfusion bags (10-19 bags: 1.015, ≥20 bags: 0.979) + clinical diagnosis (lymphoma: 1.81, leukemia: 3.208, liver cancer: 1.714). Application effect evaluation: The AUC (area under the curve), cut-off point, corresponding sensitivity and specificity of female and male platelet transfusion effect prediction models were 0.868, -0.354, 68.75%, 89.84% and 0.854, -0.942, 81.36%, 77.53%, respectively. Actual application results showed that the sensitivity, specificity, and accuracy of female and male model were 89.47%, 92.74%, 91.98% and 83.72%, 91.47%, 89.53%, respectively. 【Conclusion】 There is high incidence of platelet transfusion refractoriness in tumor patients, and the predictive model has good prediction effect on platelet transfusion refractoriness in tumor patients, which can provide reliable basis for accurate platelet transfusion in tumor patients.

Application of CT pulmonary angiography in acute pulmonary embolism and right heart function / 中国康复理论与实践

ObjectiveTo explore the application value of CT pulmonary angiography (CTPA) in assessing the severity of acute pulmonary embolism (APE) and right heart function in rehabilitation patients. MethodsFrom January, 2013 to January, 2020, 133 inpatients (94 positive and 39 negative) who underwent CTPA examination in Beijing Bo'ai Hospital were involved. Positive patients were further divided into mild, moderate and severe groups based on the pulmonary artery obstruction index (PAOI). The clinical parameters and right heart function indicators were compared. Spearman correlation analysis was used to analyze the correlation between PAOI, and clinical parameters and right heart function indicators, and Logistic regression analysis was used to predict the risk factors of APE. ResultsThere was significant difference in lower extremity venous thrombosis, D-dimer, oxygen partial pressure, PAOI and left process of interventricular septum among four groups (H ≥ 12.350, P < 0.01). PAOI was moderately positively correlated with D-dimer (r = 0.443, P < 0.001) and left process of interventricular septum (r = 0.520, P < 0.001), and was weakly positively correlated with lower extremity venous thrombosis (r = 0.399, P < 0.001), left pulmonary artery diameter (r = 0.213, P = 0.014) and inferior vena cava regurgitation (r = 0.229, P = 0.008). Lower extremity venous thrombosis (OR = 7.708, P < 0.001) and left process of interventricular septum (OR = 3.641, P = 0.008) were independent risk factors for the onset of APE. The combination of the two indicators was effective for diagnosis of APE, and AUC was 0.795 (95% CI 0.715 to 0.874). ConclusionCTPA may be applied to evaluate the severity of APE and right heart function in rehabilitation patients.

Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry / 대한뇌졸중학회지

Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.