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: Current 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 4228 treatment-naïve patients with lung cancer who underwent targeted 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; 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-TKIs treatment. CONCLUSION: Co-occurring EGFR p.E709X mutation mediates 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 co-existing 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Effects of sodium arsenite on proliferation, apoptosis and Hippo-YAP pathway of PC12 cells / 中国药理学通报

To investigate the effects of sodium arsenite(NaAsO

Analysis of clinical features and risk factors of necrotizing pneumonia in children / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical characteristics and risk factor analysis of necrotizing pneumonia in children.@*METHODS@#A retrospective study was used to analyze the case data of 218 children with severe pneumonia hospitalized in the Department of Respiratory Medicine, Children's Hospital of Capital Institute of Pediatrics from January 2016 to January 2020, and they were divided into 96 cases in the necrotizing pneumonia group (NP group) and 122 cases in the non-necrotizing pneumonia group (NNP group) according to whether necrosis of the lung occurred. The differences in clinical characteristics (malnutrition, fever duration, hospitalization time, imaging performance, treatment and regression follow-up), laboratory tests [leukocytes, neutrophil ratio, platelet (PLT), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and lactate dehydrogenase (LDH)] and bronchoscopic performance between the two groups were compared, and Logistic regression analysis of clinical risk factors associated with necrotizing pneumonia was performed to further determine the maximum diagnostic value of each index by subject operating characteristic curve (ROC). The critical value of each index was further determined by the ROC.@*RESULTS@#The differences in age, gender, pathogenic classification, and bronchoscopic presentation between the two groups of children were not statistically significant (P>0.05); whereas the imaging uptake time of the children in the NP group was higher than that in the NNP group (P < 0.05). The differences in malnutrition, fever duration, length of stay, white blood cell count, neutrophil ratio, CRP, PCT, and D-dimer were statistically significant between the two groups (P < 0.05). The imaging uptake time was lower in children under 6 years of age than in those over 6 years of age, and the imaging uptake time for bronchoalveolar lavage within 10 d of disease duration was lower than that for those over 10 d; the imaging uptake time was significantly longer in the mixed infection group than that in the single pathogen infection group. Logistic regression analysis of the two groups revealed that the duration of fever, hospital stay, CRP, PCT, and D-dimer were risk factors for secondary pulmonary necrosis (P < 0.001, P < 0.001, P < 0.001, P=0.013, P=0.001, respectively). The ROC curves for fever duration, CRP, PCT, and D-dimer were plotted and found to have diagnostic value for predicting the occurrence of pulmonary necrosis when fever duration >11.5 d, CRP >48.35 mg/L, and D-dimer > 4.25 mg/L [area under ROC curve (AUC)=0.909, 0.836, and 0.747, all P < 0.001].@*CONCLUSION@#Children with necrotizing pneumonia have a longer heat course and hospital stay, and the imaging uptake time of mixed pathogenic infections is significantly longer than that of single pathogenic infections. Children with necrotizing pneumonia under 6 years of age have more advantageous efficacy of electronic bronchoscopic alveolar lavage within 10 d of disease duration compared with children in the group over 6 years of age and children in the group with disease duration >10 d. Inflammatory indexes CRP, PCT, and D-dimer are significantly higher. The heat course, CRP, PCT, and D-dimer are risk factors for secondary lung necrosis in severe pneumonia. Heat course >11.5 d, CRP >48.35 mg/L, and D-dimer >4.25 mg/L have high predictive value for the diagnosis of necrotizing pneumonia.

Xiaojindan Extract Modulated Macrophage Polarization by Targeting PI3K/Akt Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Xiaojindan extract （XJD） on macrophage polarization. MethodLipopolysaccharide （LPS） and interleukin-4 （IL-4） were used to induce M1 and M2 polarization of RAW264.7 cells. The influence of 10-80 mg·L-1 XJD on cell proliferation was detected by Cell Counting Kit-8 （CCK-8） assay. Nitric oxide （NO） and interleukin-6 （IL-6） release was explored by Griess assay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA expression of M1 and M2 macrophage markers was measured by real-time quantitative polymerase chain reaction （Real-time PCR）， and the CD206+ expression was determined by flow cytometry. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway was analyzed by western blot. Result10-80 mg·L-1 XJD showed no marked cytotoxicity in LPS （0.5 mg·L-1）- or IL-4 （20 μg·L-1）-induced RAW264.7 cells. Compared with the control group， LPS significantly promoted the expression of M1 macrophage markers （P<0.01）， including increased NO and IL-6 release （P<0.01） and upregulated mRNA expression of interleukin-1β （IL-1β）， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX-2） and tumor necrosis factor-α （TNF-α） （P<0.01）. Compared with LPS-induced group， 20-80 mg·L-1 XJD decreased the release of NO and IL-6 in a dose-dependent manner （P<0.01）， and similarly 10-80 mg·L-1 XJD suppressed the mRNA expression of IL-1β， iNOS， COX-2 and TNF-α （P<0.01）. Compared with the control group， IL-4 obviously increased the expression of M2 macrophage markers （P<0.01）， including increased CD206+ cell population and upregulated mRNA expression of arginine-1 （Arg-1）， interleukin-10 （IL-10）， interleukin-13 （IL-13） and transforming growth factor-β1 （TGF-β1）. Compared with IL-4-induced group， 10-80 mg·L-1 XJD dose-dependently decreased CD206+ cell population （P<0.01） and inhibited the mRNA expression of Arg-1， IL-10， IL-13 and TGF-β1 （P<0.01）. Western blot showed that XJD significantly downregulated the activation of PI3K/Akt pathway as compared to LPS- and IL-4-induced groups （P<0.05， P<0.01）. ConclusionXJD significantly inhibited the macrophage polarization in the LPS- and IL-4-induced RAW264.7 cells by targeting PI3K/Akt pathway.