Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC.

PURPOSE: The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X-mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4,228 treatment-naïve patients with lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib (n = 37) and the third-generation EGFR-TKIs (n = 31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. RESULTS: Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC (∼30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI [G719X/E709X vs. G719X; objective response rate (ORR): 0.00% vs. 47.62%, P < 0.001; mPFS: 7.18 vs. 14.2 months, P = 0.04, respectively]. Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients (G719X/E709X vs. G719X; ORR: 71.43% vs. 56.67%, P = 0.99; mPFS: 14.7 vs. 15.8 months, P = 0.69, respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKI treatment. CONCLUSIONS: Co-occurring EGFR p.E709X mutation mediated primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the coexisting EGFR p.E709X mutation status.

Integrated bioinformatics analysis identifies autophagy-associated genes as candidate biomarkers and reveals the immune infiltration landscape in psoriasis.

Autophagy is implicated in the pathogenesis of psoriasis. We aimed to identify autophagy-related biomarkers in psoriasis via an integrated bioinformatics approach. We downloaded the gene expression profiles of GSE30999 dataset, and the "limma" package was applied to identify differentially expressed genes (DEGs). Then, differentially expressed autophagy-related genes (DEARGs) were identified via integrating autophagy-related genes with DEGs. CytoHubba plugin was used for the identification of hub genes and verified by the GSE41662 dataset. Subsequently, a series of bioinformatics analyses were employed, including protein-protein interaction network, functional enrichment, spearman correlation, receiver operating characteristic, and immune infiltration analyses. One hundred and one DEARGs were identified, and seven DEARGs were identified as hub genes and verified using the GSE41662 dataset. These validated genes had good diagnostic value in distinguishing psoriasis lesions. Immune infiltration analysis indicated that ATG5, SQSTM1, EGFR, MAPK8, MAPK3, MYC, and PIK3C3 were correlated with infiltration of immune cells. Seven DEARGs, namely ATG5, SQSTM1, EGFR, MAPK8, MAPK3, MYC, and PIK3C3, may be involved in the pathogenesis of psoriasis, which expanded the understanding of the development of psoriasis and provided important clinical significance for treatment of this disease.

Identifying the effective combination of acupuncture and traditional Chinese medicinal herbs for postmenopausal osteoporosis therapy through studies of their molecular regulation of bone homeostasis.

Worldwide, as the population age, osteoporosis is becoming increasingly common, and osteoporotic fractures have a significant economic burden. Postmenopausal women are the most susceptible to developing osteoporosis and the most critical time to prevent it is during the perimenopausal and early menopausal years. In this regard, we hypothesize rational combination of acupuncture and Traditional Chinese Medicine (TCM) in the form of herbal extract could prevent osteoporosis in women. Estrogen deficiency during menopause causes low-level inflammation that stimulates the formation of osteoclasts, the bone-resorbing cells, and simultaneously inhibits the viability and function of osteoblasts, the bone-forming cells. The most potent inflammatory cytokine in skeletal homeostasis is the receptor activator of nuclear factor kappa B ligand (RANKL) that stimulates osteoclast function. Conversely, the canonical Wnt pathway is essential for osteoblastogenesis and bone formation, and estrogen deficiency leads to diminished functioning of this pathway. TCM and acupuncture could target the RANKL and the Wnt pathway in favorable ways to prevent the accelerated bone loss experienced during the early menopausal stage and promote the gain in bone mass in postmenopausal women. In this review, we propose a rational combination of specific TCM and acupuncture targeting those signaling molecules/pathways by the drugs that are in clinical use for the treatment of postmenopausal osteoporosis. Our rational approach revealed that Danshen (Radix Salviae Miltiorrhizae) could exert a synergistic effect with acupuncture. We then propose a translational path for developing the putative combination in women with postmenopausal osteoporosis to curtail the risk of osteoporotic fractures.

Deep learning technology for quality control of echocardiography images / 实用医学杂志

Objective To Explore the feasibility and value of deep learning technology for quality control of echocardiography images.Methods A total of 180985 echocardiography images collected from Sichuan Provin-cial People's Hospital between 2015 and 2022 were selected to establish the experimental dataset.Two task models of the echocardiography standard views quality assessment method were trained,including intelligent recognition of seven types of views(six standard views and other views)and quality scoring of six standard views.The predictions of the models on the test set were compared with the results of the sonographer's annotation to assess the accuracy,feasibility,and timeliness of the runs of the two models.Results The overall classification accuracy of the stan-dard views recognition model was 98.90%,the precision was 98.17%,the recall was 98.18%and the F1 value was 98.17%,with the classification results close to the expert recognition level;the average PLCC of the six standard views quality scoring models was 0.933,the average SROCC was 0.929,the average RMSE was 7.95 and the average MAE was 4.83,and the prediction results were in strong agreement with the expert scores.The single-frame inference time after deployment on the 3090 GPU was less than 20 ms,meeting real-time requirements.Conclusion The echocardiography standard views quality assessment method can provide objective and accurate quality assessment results,promoting the development of echocardiography image quality control management towards real-time,objective,and intelligent.

Predictors of a forgotten joint after medial open wedge high tibial osteotomy / 中国组织工程研究

BACKGROUND:Medial open wedge high tibial osteotomy is an effective procedure for preserving the knee joint in patients with medial compartmental osteoarthritis.Previous studies have demonstrated that the forgotten joint score provides a lower ceiling effect and consistency of medial open wedge high tibial osteotomy outcomes compared to traditional assessment tools. OBJECTIVE:To identify predictive factors associated with the occurrence of a forgotten joint after medial open wedge high tibial osteotomy. METHODS:117 patients with medial open wedge high tibial osteotomy who were treated at First Affiliated Hospital of Guangzhou University of Chinese Medicine were selected,including 35 males and 82 females,with an average age of 61 years.They were followed up for at least 2 years.Patients were divided into a forgotten joint group(n=28)and a non-forgotten joint group(n=89)by evaluating whether they achieved forgotten joint after surgery.Univariate and multivariate logistic regression analyses were performed with preoperative patient characteristics and surgery-related factors as potential predictors. RESULTS AND CONCLUSION:(1)There were significant differences in the proximal medial tibial angle between the two groups before surgery(P<0.05).There were significant differences in the forgotten joint score,Knee Injury and Osteoarthritis Outcome Score,knee society knee score,function score,and patients joint perception between the two groups after surgery(P<0.05).There was a significant difference between the hip-knee-ankle angle and the medial proximal tibial angle after operation(P<0.05).(2)Univariate Logistic regression analysis showed that the medial proximal tibial angle had a significant influence on the forgotten joint before operation[OR=0.755,95%CI(0.635-0.897),P<0.001].There were significant effects on the forgotten joint of hip-knee-ankle angle and medial proximal tibial angle[OR=1.546,95%CI(1.242-1.924),P<0.001;OR=0.815,95%CI(0.713-0.931),P=0.003].(3)Multivariate logistic regression analysis showed that preoperative K-L grade 1 was a favorable factor for obtaining forgotten joints.Preoperative medial proximal tibial angle and postoperative hip-knee-ankle angle were independent predictors of forgetting joints,and they had a curvilinear relationship with the probability of achieving forgetting joints.When preoperative medial proximal tibial angle increased by 1°,the probability of achieving a forgotten joint decreased by 27.7%[OR=0.723,95%CI(0.593-0.882),P<0.001].Conversely,when postoperative hip-knee-ankle angle increased by 1°,the probability of achieving a forgotten joint increased by 46.4%[OR=1.464,95%CI(1.153-1.860),P=0.002].(4)The results showed that patients with preoperative knee osteoarthritis K-L grade 1,small medial proximal tibial angle(<85.5°),and large postoperative hip-knee-ankle angle(>176.0°)were predictors of forgotten joint.

Study on Mechanism of Xiaojin Pills in Treatment of Breast Cancer Based on Network Pharmacology and Experimental Verification / 中国中医药信息杂志

Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

A multicenter case-control study on postoperative intestinal fistula in Chinese patients with Crohn disease.

The aim of this study was to (1) assess the independent factors affecting patients with postoperative intestinal fistula from Crohn disease (CD) by analyzing preoperative clinical data, (2) establish a nomogram prediction model for this condition based on these factors, and (3) validate this model and evaluate its accuracy. In this retrospective multicenter case-control study, the clinical data of 240 patients with CD admitted for surgical treatment between September 2019 and September 2021 at 3 centers were collected. Patients were randomly divided into a training set (168 patients) and a validation set (72 patients). Univariate analysis was performed for relevant factors, and statistically significant factors were then analyzed using multivariate logistic regression to determine the independent influencing factors. A nomogram model for predicting postoperative intestinal fistula in patients with CD was constructed and the accuracy of the model was evaluated using calibration curves. Univariate analysis showed that disease behavior, abdominal abscess, intestinal perforation, neutrophil-to-lymphocyte ratio, systemic immunoinflammatory index, and prognostic nutrition index were factors affecting postoperative intestinal fistula in patients with CD. Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratio, prognostic nutrition index, disease behavior, and Crohn disease activity index score were independent influencing factors. After assessing the validation set, the area under the curve was 0.899, indicating good predictive accuracy of the nomogram model. The prediction model developed in this study can effectively predict the risk of postoperative intestinal fistula.

Single-cell data analysis of malignant epithelial cell heterogeneity in lung adenocarcinoma for patient classification and prognosis prediction.

Lung cancer is one of the leading causes of cancer-related death. Most advanced lung adenocarcinoma (LUAD) patients have poor survival because of drug resistance and relapse. Neglecting intratumoral heterogeneity might be one of the reasons for treatment insensitivity, while single-cell RNA sequencing (scRNA-seq) technologies can provide transcriptome information at the single-cell level. Herein, we combined scRNA-seq and bulk RNA-seq data of LUAD and identified a novel cluster of malignant epithelial cells - KRT81+ malignant epithelial cells - associated with worse prognoses. Further analysis revealed that the hypoxia and EMT pathways of these cells were activated to predispose them to differentiate into metastatic lung adenocarcinoma cells. Finally, we also studied the role of these tumor cells in the immune microenvironment and their role in the classification and prognosis prediction of lung adenocarcinoma patients.

[Rapid extraction and detection of five alkaloids in dried khat by solvent extraction-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Khat is a common plant that grows primarily in Eastern Africa and the Arabian Peninsula. Cathinone, norpseudoephedrine, and norephedrine are the main psychoactive components of khat. Experimental studies have shown that red and green khat have similar cathinone contents, but green khat contains more norpseudoephedrine and norephedrine than red khat. Research indicates that Ethiopians believe that red khat has stronger psychoactive effects than green khat. Therefore, we speculated that other substances in red khat may enhance its psychoactive effects. Using the sampling method, we identified two other psychoactive components in khat: methcathinone and ethcathinone. At present, only a few studies on the extraction and detection of alkaloids from khat have been published in China, and no reports on the extraction and detection of methcathinone and ethcathinone from khat are available. In this study, we established an extraction and detection method for five alkaloids in dried khat using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS). To establish the extraction method, we optimized the extraction solvent and process. The amounts of dichloromethane and sodium hydroxide added during the purification step were also optimized. To establish the detection method, we optimized the chromatographic and MS conditions. The final extraction and detection method was as follows: Dried khat powder (0.1 g) was loaded into a polypropylene centrifuge tube, added with 1 mL of 0.05 mol/L hydrochloride aqueous solution, and vortex-oscillated for 3 min for extraction. The sample was centrifuged at 10000 r/min for 3 min. Next, 600 µL of the supernatant was placed in a centrifuge tube, added with 1 mL of dichloromethane, shaken for 1 min, and centrifuged at 10000 r/min for 3 min. Subsequently, 300 µL of the supernatant was placed in a centrifuge tube, added with 80 µL of 1 mol/L sodium hydroxide aqueous solution, shaken for 1 min, and added with 1 mL of acetonitrile. Vortex oscillation was performed for 2 min to extract the sample, after which solid sodium chloride (0.4 g) was added to the mixture, followed by shaking for 1 min to separate the acetonitrile and aqueous phases. The mixture was then centrifuged at 10000 r/min for 3 min. Finally, the supernatant was collected and diluted for further testing. The five target analytes were separated on a ZORBAX Eclipse Plus Phenyl-Hexyl column (100 mm×3.0 mm, 1.8 µm) via gradient elution using 0.1% acetic acid aqueous solution and acetonitrile as mobile phases with a flow rate of 0.3 mL/min and column temperature of 30 ℃. The analytes were identified using the targeted MS/MS method under positive electrospray ionization mode and quantified using the external standard method. The five alkaloids showed good correlations (all correlation coefficients (r2)≥0.9976) with their respective linear ranges. The limits of detection were between 0.08 and 0.75 µg/L, and the limits of quantification were between 0.25 and 2.50 µg/L. The average recoveries of the five alkaloids from two plants with different alkaloid contents were between 90.7% and 105.2%. The intra-sample precision ranged from 0.5% to 2.3%, the intra-day precision was between 1.0% and 2.5%, and the inter-day precision was between 1.3% and 3.3%. Using the developed method, we extracted and analyzed 15 khat samples, and detected five alkaloids. This method enables rapid sample pretreatment and has high sensitivity, good stability, and suitable accuracy. Based on the above results, we conclude that the proposed method meets the inspection and identification requirements for khat. Thus, it can provide a valuable reference for the physical and chemical identification of khat and support for further studies on its psychoactive components.

Detoxification Mechanism of Combined Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta in Regulating Cardiac Metabolic Enzyme CYP2J3 / 中国实验方剂学杂志

ObjectiveTo investigate the detoxification mechanism of Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta， and their effective components ellagic acid， liquiritin and aconitine based on cardiac cytochrome P450 （CYP450） system. MethodIn in vivo experiments， rats were randomly divided into control group， prepared Aconiti Kusnezoffii Radix Cocta group （0.25 g·kg-1）， Chebulae Fructus group （0.252 g·kg-1）， Glycyrrhizae Radix et Rhizoma group （0.25 g·kg-1） and combination group （0.25 g·kg-1 Chebulae Fructus+0.25 g·kg-1 Glycyrrhizae Radix et Rhizoma+0.25 g·kg-1 prepared Aconiti Kusnezoffii Radix Cocta， with prepared Aconiti Kusnezoffii Radix Cocta as standard）. After 8 days of administration， creatine kinase （CK） and lactate dehydrogenase （LDH） in rats were detected to observe the pathological changes of heart tissue. Real-time PCR and Western blot were performed to detect the mRNA and protein expressions of CYP2J3， respectively. In in vitro experiments， control group， aconitine group， ellagic acid group， liquiritin group and combination group （aconitine+ellagic acid+liquiritin） were set， and their effects on cell number， DNA content， reactive oxygen species （ROS） and mitochondrial membrane potential （MMP） were detected by high content analysis. The changes in the mRNA and protein expressions of CYP2J3 were also observed. ResultIn vivo experiments， compared with the control group， the prepared Aconiti Kusnezoffii Radix Cocta group had increased CK and LDH in serum （P<0.05， P<0.01）， while the combination group had decreased activities of CK and LDH. Additionally， pathological staining results showed that Chebulae Fructus and Glycyrrhizae Radix et Rhizoma reduced the cardiac toxicity caused by prepared Aconiti Kusnezoffii Radix Cocta. Real-time PCR found that compared with the control group， prepared Aconiti Kusnezoffii Radix Cocta down-regulated the mRNA level of CYP2J3 （P<0.05）， while up-regulated that expression when used in combination with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma （P<0.01）. The protein and mRNA translation levels were basically consistent. In vitro experiments， high content analysis revealed that there was a decrease in the cell number， DNA content and MMP fluorescence value of the aconitine group （P<0.01） and the combination group （P<0.05， P<0.01）， and the fluorescence value of the combination group was higher than that of the aconitine group. Moreover， aconitine down-regulated the mRNA level of CYP2J3 （P<0.05）， but the down-regulating ability of aconitine was reversed in the combination group （P<0.05）. ConclusionThe detoxification mechanism of combined Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and prepared Aconiti Kusnezoffii Radix Cocta is mainly that the combination of ellagic acid， liquiritin and aconitine can up-regulate the expression of CYP2J3， and promote the metabolism of arachidonic acid （AA） to produce epoxyeicosatrienoic acids （EETs）， thus reducing the cardiac toxicity， and this effect may start from the transcriptional link.

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders / 神经科学通报·英文版

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.

Study on the effects and mechanism of Guiling Gao on the activity state of rats with damp-heat syndrome / 国际中医中药杂志

Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.

Efficacy comparison between pneumovesicoscopic Cohen and Politano-Leadbetter technique in transvesicoscopic ureteral reimplantation in children / 中华实用儿科临床杂志

Objective:To compare the efficacy of pneumovesicoscopic Cohen and Politano-Leadbetter procedures in the treatment of vesicoureteral junction obstruction (VUJO) in children.Methods:The data of 48 children with VUJO who underwent operations in the Department of Urology, Anhui Provincial Children′s Hospital from January 2017 to December 2021 were retrospectively analyzed.According to the operation time, the patients were divided into the pneumovesicoscopic Cohen group(group C) (28 cases) and pneumovesicoscopic Politano-Leadbetter group(group P) (20 cases). The operation time, postoperative urinary catheterization duration, hematuria duration, hospitalization time, and the improvement of hydronephrosis, ureteral dilatation, and renal function after surgery were compared between the 2 groups.The enumeration data were compared by the χ2 test or Fisher′ s exact probability method.The measurement data were compared by the t-test. Results:All the 48 children were successfully operated on by the same surgeon, without conversion to open surgery.Six cases in the group C had a megaureter and underwent ureter tailoring.Two cases in the group P had calyceal and ureteral calculi, which were all removed after operation.There was a statistically significant difference in the operation time between group C and group P[(136.5±35.4) min vs.(165.8±33.2) min, t=-3.154, P=0.002]. The patients were followed up for (10.3±2.6) months after operation.There were 8 cases and 6 cases of urinary tract infection in group C and group P within 2 months after the operation, respectively.They all improved after conservative anti-infection treatment, and the infection was well controlled after removal of the D-J tube.Besides, their intravenous pyelography 6 months after operation showed that the ureter was unobstructed.In group C, 6 months after the operation, the anterior and posterior diameters of the renal pelvis [(1.62±0.54) cm vs.(2.55±1.24) cm, t=-5.027, P=0.001] and the largest diameter of the ureter [(0.95±0.27) cm vs.(1.51±0.52) cm, t=-8.495, P<0.001] were significantly decreased, compared with those before operation.However, the renal cortex thickness was increased significantly [(1.47±0.25) cm vs.(0.86±0.46) cm, t=2.028, P=0.004], and the renal function (as indicated by the diuretic nephrogram) was notably improved [(46.27±2.16)% vs.(41.83±3.04)%, t=1.647, P=0.030]. In group P, 6 months after operation, the anterior and posterior diameters of the renal pelvis[(1.48±0.82) cm vs.(2.68±1.41) cm, t=-2.740, P=0.003] and the maximum diameter of the ureter [(1.05±0.46) cm vs.(1.36±0.27) cm, t=-1.635, P=0.040] were significantly smaller than those before operation.However, the renal cortical thickness was increased [(1.38±0.33) cm vs.(0.74±0.39) cm, t=9.073, P<0.001], and the renal function (as indicated by the diuretic nephrogram) was significantly improved [(45.18±3.35)% vs.(39.55±2.49)%, t=1.277, P=0.030]. Politano-Leadbetter surgery outperformed Cohen surgery in promoting the recovery of the anterior and posterior diameters of the renal pelvis [(1.48±0.82) cm vs.(1.62±0.54) cm, t=-1.748, P=0.030]. Conclusions:Pneumovesicoscopic Politano-Leadbetter operation can establish a longer submucosal tunnel without changing the ureteral shape and opening position, having good effects in treating VUJO combined with calyceal and ureteral calculi.Pneumovesicoscopic Politano-Leadbetter operation can also better improve postoperative recovery from hydronephrosis than Cohen operation.However, the pneumovesicoscopic Politano-Leadbetter operation is more difficult and requires longer time.The surgeon should choose a reasonable operation based on his/her own experience.

Expression of SEC61G in Oral Squamous Cell Carcinoma and Its Prognostic Value / 肿瘤防治研究

Objective To analyze the expression of SEC61G in oral squamous cell carcinoma (OSCC) tissues and cell lines and determine its correlations with the clinicopathological features and prognosis of patients with OSCC. Methods The expression of SEC61G in OSCC tissues and its diagnostic and prognostic value were detected in the TCGA database. The expression levels of SEC61G in paraffin-embedded OSCC tissues and adjacent normal tissue specimens of 64 patients with OSCC were detected by immunohistochemistry. The correlation of SEC61G expression in OSCC tissues with the clinicopathological features was analyzed. Kaplan-Meier survival curve analysis showed that the expression of SEC61G correlated with the overall survival time of patients with OSCC. Cox regression analysis was used to analyze prognostic influence factors. Results The expression of SEC61G in OSCC tissues was significantly higher than that in para-carcinoma tissues (P < 0.05), consistent with the results of the TCGA database analysis, and its expression was closely related to N stage and clinical stage (P < 0.05). The overall survival of patients with OSCC in the group with low SEC61G expression was significantly higher than that in the high SEC61G expression group (P < 0.05). N stage and SEC61G expression were the prognostic influence factors for patients with OSCC (P < 0.05). SEC61G expression was an independent predictor of the prognosis of patients with OSCC (P < 0.05, AUC=0.923). Conclusion SEC61G is highly expressed in OSCC tissues and associated with N stage and clinical stage. Its high expression is associated with poor prognosis of patients. It may be a diagnostic biomarker for OSCC.

Research progress on natural guaiane-type sesquiterpenoids and their biological activities / 中国中药杂志

Guaiane-type sesquiterpenoids are a class of terpenoids with [5,7] ring-fused system as the basic skeletal structure composed of three isoprene units, which are substituted by 4,10-dimethyl-7-isopropyl. According to the difference in functional groups and degree of polymerization, they can be divided into simple guaiane-type sesquiterpenoids, sesquiterpene lactones, sesquiterpene dimers, and sesquiterpene trimers. Natural guaiane-type sesquiterpenoids are widely distributed in plants, fungi, and marine organisms, especially in families such as Compositae, Zingiberaceae, Thymelaeaceae, Lamiaceae, and Alismataceae. Guaiane-type sesquiterpenoids have good antibacterial, anti-inflammatory, anticancer, and neuroprotective effects. In this paper, the novel guaiane-type sesquiterpenoids isolated and identified in recent 10 years(2013-2022) and their biological activities were reviewed in order to provide refe-rences for the research and development of guaiane-type sesquiterpenoids.

Functional Autapses Form in Striatal Parvalbumin Interneurons but not Medium Spiny Projection Neurons / 神经科学通报·英文版

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr2+. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABAA receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.

Aberrant Inter-hemispheric Connectivity in Patients With Recurrent Major Depressive Disorder: A Multimodal MRI Study.

Objective: Inter-hemispheric network dysconnectivity has been well-documented in patients with recurrent major depressive disorder (MDD). However, it has remained unclear how structural networks between bilateral hemispheres relate to inter-hemispheric functional dysconnectivity and depression severity in MDD. Our study attempted to investigate the alterations in corpus callosum macrostructural and microstructural as well as inter-hemispheric homotopic functional connectivity (FC) in patients with recurrent MDD and to determine how these alterations are related with depressive severity. Materials and Methods: Resting-state functional MRI (fMRI), T1WI anatomical images and diffusion tensor MRI of the whole brain were performed in 140 MDD patients and 44 normal controls matched for age, sex, years of education. We analyzed the macrostructural and microstructural integrity as well as voxel-mirrored homotopic functional connectivity (VMHC) of corpus callosum (CC) and its five subregion. Two-sample t-test was used to investigate the differences between the two groups. Significant subregional metrics were correlated with depression severity by spearman's correlation analysis, respectively. Results: Compared with control subjects, MDD patients had significantly attenuated inter-hemispheric homotopic FC in the bilateral medial prefrontal cortex, and impaired anterior CC microstructural integrity (each comparison had a corrected P < 0.05), whereas CC macrostructural measurements remained stable. In addition, disruption of anterior CC microstructural integrity correlated with a reduction in FC in the bilateral medial prefrontal cortex, which correlated with depression severity in MDD patients. Furthermore, disruption of anterior CC integrity exerted an indirect influence on depression severity in MDD patients through an impairment of inter-hemispheric homotopic FC. Conclusion: These findings may help to advance our understanding of the neurobiological basis of depression by identifying region-specific interhemispheric dysconnectivity.

Research into tibial tunnel location in reconstruction of posterior cruciate ligament / 中华创伤骨科杂志

Posterior cruciate ligament (PCL) injury is common in sports medicine. Arthroscopic reconstruction of PCL has become a routine procedure to stabilize the knee joint after PCL injury. The location of tibial tunnel during operation is crucial to a successful surgery. This article reviews the current studies on transtibial PCL reconstruction from the aspects of the anatomy related to the tibial tunnel, the anteromedial and anterolateral tibial tunnels, the maximum angle and optimal angle of tibial tunnel, and the anatomical and non-anatomical tibial tunnels, hoping to provide helpful references for the treatment of PCL injury.

Bacterial culture of pancreatic juice in early stage of severe acute pancreatitis / 中华普通外科杂志

Objective:To investigate the distribution, drug resistance and clinical significance of bacteria and fungi in pancreatic juice of patients with severe acute pancreatitis (SAP).Methods:Data of patients with severe acute pancreatitis receiving ERCP treatment and pancreatic juice bacterial culture at Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University from Jan 2019 to Jun 2020 were retrospectively analyzed.Results:A total of 97 patients were included. Pathogens were isolated from 46 (47.42%) pancreatic juice samples, with 71 strains including 43 (60.56%) gram negative bacteria, 26 (36.62%) gram positive bacteria, and 2 (2.82%) fungi. The C-reactive protein (CRP), D-dimer and Balthazar CT Score in the culture positive group were higher than those in the culture negative group ( P < 0.05). The incidence of complications and pancreatic infection in the culture positive group was also significantly higher ( P < 0.05). Conclusions:The positive rate of pancreatic juice bacterial culture in the early stage of severe acute pancreatitis is high, in which Gram-negative bacteria are most common, followed by Gram-positive bacteria and fungi. The presence of pathogens in pancreatic juice predicts ensuing infections.