The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

BACKGROUND:Cannabidiol is effective in ameliorating the body's inflammatory response,but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise. OBJECTIVE:To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into six groups:blank control group,exercise coconut oil group,exercise control group,50 mg/kg cannabidiol group,60 mg/kg cannabidiol group,and 70 mg/kg cannabidiol group,with six rats in each group.Except for rats in the blank control group,rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model.At the end of each swimming exercise,rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations(50,60,and 70 mg/kg)by gavage;rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day;and rats in the blank control group and the exercise control group were not given any special treatment.The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques.Differentially expressed genes obtained were subjected to KEGG analysis,and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. RESULTS AND CONCLUSION:The results of ELISA showed that the contents of interleukin-6(P<0.05),tumor necrosis factor-α(P<0.01),interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group.After cannabidiol intervention,the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration.By comparing GO and KEGG databases,the functional properties of differentially expressed genes were analyzed,and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway.RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results.To conclude,cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.

Salivary gland tumor is one of the most common tumors in oral and maxillofacial regions. The diagnosis and treatment of salivary gland tumors had been a clinical characteristic project in Peking University School and Hospital of Stomatology since long time ago. Here we introduced the research progress in diagnosis and treatment of salivary gland tumors during the past 10 years. Among 7 190 cases of salivary gland tumors treated in this institution, 4 654 cases (64.7%) were benign, and 2 536 (35.3%) were malignant, with benign ∶ malignant ratio of 1.84 ∶ 1. Parotid was the most common location, followed by minor salivary gland and submandibular gland, while sublingular gland tumor was seldom seen. The proportion of minor salivary gland tumor was relatively high. Among 1 874 cases with primary malignant tumors, the cases with T3 and stage Ⅲ accounted for only 9.6% and 10.3%, respectively, which indicated that there was shortcoming in the T classification and clinical stage formulated by Union for International Cancer Control (UICC), and further revision was required. The 5, 10, and 15 year survival rates of 1 637 cases with postoperative follow-up were 93.1%, 87.2% and 79.3%, respectively, which were much higher than those we reported 30 years ago. The improvement of treatment results was related to more widely used combined treatment with surgery and postoperative radiotherapy, and the increase in patients with early stage. Adenoid cystic carcinoma was the malignant tumor with high rate of distant metastasis. The 5 and 10 year survival rates of the patients with pulmonary metastasis were 76.2% and 51.8%, respectively, which indicated that the pulmonary metastatic carcinomas developed slowly. Recurrent rate of carcinoma ex pleomorphic adenoma was 46.7% after single treatment of sur-gery, while it decreased to 27.5% after combined theraphy with surgery and radiotherapy, indicating that postoperative radiotheraphy could reduce the recurrent rate effectively. The normal myoepithelial cells had the inhibiting role in the invasion and metastasis of carcinoma ex pleomorphic adenoma. The evaluation of integrity of myoepithelial cells surrounding the tumor mass is helpful to understand the invasiveness of the tumors. The new surgical modalities such as extracapsular resection and partial sialoadenectomy were used in treatment of benign tumors of parotid gland and submandibular gland with advantages of decreased tissue damage and preservation of glandular function. Application of digital surgical techniques such as mixed reality combined with surgical navigation and real-time three-dimensional holograms in the surgical treatment of parotid gland tumors showed the benifits of more safety and precision, and less tissue da-mage.
Humans ; Salivary Gland Neoplasms/pathology* ; Carcinoma, Adenoid Cystic/therapy* ; Adenoma, Pleomorphic/therapy* ; Neoplasm Staging

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Pyoderma gangrenosum(PG)is a rare autoinflammatory disease,characterized mainly by painful and necrotic skin ulcers.The etiology of PG is unknown,and its treatment is quite challenging.This article reports a case of recurrent pyoderma gangrenosum successfully treated with adalimumab combined with tofacitinib,along with a review of relevant literature.The patient,a 54-year-old male,presented with scrotal ulcers accompanied by pain for 20 days,worsening and involving the groin area for 5 days,and fever for 1 day.Dermatological examination revealed two painful ulcers on the scrotum with raised edges,clear boundaries,and a small amount of purulent discharge on the surface;the right groin area and the medial left thigh showed irregular infiltrative erythematous plaques,with scattered clustered pustules on them,central necrosis appearing purplish-brown,surrounded by a red halo with clear boundaries.Based on the patient's past medical history,clinical manifestations,and auxiliary examinations,the diagnosis was consistent with pyoderma gangrenosum.After treatment with adalimumab combined with tofacitinib,the patient's symptoms were significantly improved,and the ulcers healed.At the 6-month follow-up,the skin lesions had not recurred.For refractory PG that is ineffective to conventional treatments,adalimumab combined with tofacitinib is an effective and safe treatment option,providing a new combination therapy regimen for PG.

Objective To develop and compare prediction models for hyperuricemia(HUA)in perim-enopausal and postmenopausal women using Lasso regression,random forest,and multivariate logistic regres-sion.Methods A multi-stage,stratified cluster sampling method was used to select 12 790 subjects from An-ning City,Yunnan Province.Prediction models for HUA were constructed using Lasso regression,random for-est,and multivariate logistic regression.The efficacy of the model was evaluated by accuracy,sensitivity,speci-ficity,F1 score,and area under the curve(AUC).Results LASSO regression analysis screened 19 variables for inclusion in the model,such as age,waist circumference,diastolic blood pressure,BMI,HDL-C,fasting blood glucose(FBG),etc.The accuracy rate was 0.701,the sensitivity was 0.703,the specificity was 0.680,and the F1 score was 0.806.The AUC(95%CI)was 0.770(0.748-0.792).The results of the random forest model show that variables such as creatinine,triglyceride-glucose index(TyG),TG,BMI,TC,Urea nitrogen(Urea),and ALT were relatively important,with an accuracy rate of 0.663,a sensitivity of 0.653,a specificity of 0.738,and an F1 score of 0.774.The AUC(95%CI)was 0.763(0.741-0.785).Multivariate logistic re-gression results showed that 11 variables including creatinine(Cr),TyG,BMI,Urea,and ALT were included in the model,with an accuracy rate of 0.705,a sensitivity of 0.707,a specificity of 0.686,an F1 score of 0.809,and an AUC(95%CI)of 0.771(0.749-0.793).Conclusion The overall performance of LASSO re-gression and multivariate logistic regression models is better.The random forest model has a strong variable screening ability and high specificity,and can be used as a supplement to provide more accurate predictions.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

Objective To explore the effect and mechanism of keratin 17(KRT17)on proliferation of human esophageal squamous cell line KYSE-150.Methods The correlation of KRT17 expression with the disease stage and survival of patients with esophageal squamous cell carcinoma was analyzed by GEPIA2 website.Human esophageal squamous cell line KYSE-150 was divided into control group,si-NC group,si-KRT17 group and activator group.Small interfering RNA of si-NC and si-KRT17 were transfected into cells of si-NC group and si-KRT17 group,re-spectively.Cells in the activator group were transfected with si-KRT17 and treated with 740 Y-P(PI3K/AKT/mTOR pathway activator)with a final concentration of 30 μmol/L in the medium.The cell proliferation was detec-ted by CCK-8 assay.The clonal formation was detected by clonal formation experiment.The apoptosis was detected by TUNEL staining.The cell cycle was detected by flow cytometry.The cell migration and invasion were detected by Transwell assay.The contents of glucose,lactic acid and pyruvate in cell supernatant were detected by commercially available kits.The expression of KRT17 mRNA was detected by qRT-PCR.And the expression of KRT17,GLUT1,PDK1 and LDHA,p-PI3K,PI3K,p-AKT,AKT,p-mTOR and mTOR protein were detected by Western blot.Results The expression level of KRT17 in esophageal squamous cell carcinoma tissues was significantly higher than that in normal tissues(P＜0.05).There was a statistically significant correlation between the expression level of KRT17 and the stage of esophageal squamous cell carcinoma(P＜0.05).The survival prognosis of patients with low KRT17 expression was better than that of patients with high KRT17 expression(P＜0.05).Compared with control group or si-NC group,the mRNA and protein expression of KRT17 in si-KRT17 group were decreased(P＜0.05),and the cell proliferation activity,number of clone formation,migration and invasion cells were de-creased(P＜0.05).And the lactic acid content,protein expression levels of GLUT1,PDK1 and LDHA were de-creased(P＜0.05),values of p-PI3K/PI3K,p-Akt/AKT and p-mTOR/mTOR were decreased(P＜0.05).The proportion of cells in G0/G1 phase,TUNEL positive rate,and contents of glucose and pyruvate were increased(P＜0.05).Compared with si-KRT17 group,the mRNA and protein expression levels of KRT17 in activator group were increased(P＜0.05),and the cell proliferation activity,number of clone formation,migration and in-vasion cells were increased(P＜0.05).And the lactic acid content,protein expression levels of GLUT1,PDK1 and LDHA were increased(P＜0.05),the values of p-PI3K/PI3K,p-Akt/AKT and p-mTOR/mTOR were in-creased(P＜0.05).The proportion of cells in G0/G1 phase,TUNEL positive rate,and contents of glucose and pyruvate were decreased(P＜0.05).Conclusions KRT17 is highly expressed in esophageal squamous cell car-cinoma tissues and cells.Silencing KRT17 inhibits proliferation,migration and invasion of human esophageal squamous cell line KYSE-150,and promotes apoptosis and cell cycle arrest.

As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.

Angelicae Sinensis Radix, drived from a medicinal and edible plant Angelica sinensis, with the reputation of "nine Angelica recipes out of ten". The volatile oils from Angelicae Sinensis Radix was the main medicinal component of Angelicae Sinensis Radix, mainly including benzene phthalides, terpenoids and alkanes, its chemical composition was complex. Such factors as growth environment, concoction process, extraction methods and other factors all can trigger changes in volatile oil constituents and content from Angelicae Sinensis Radix. Angelicae Sinensis Radix essential oil has diverse pharmacological activities such as anti-hypotension, protection of ischemia-reperfusion injury, asthma, anti-inflammatory and anti-cancer, etc., implying its high clinical application value. This paper reviewed the literature on the volatile oil of Angelicae Sinensis Radix in the past ten years, the chemical components of Angelicae Sinensis Radix were sorted out and the factors affecting the chemical components were summarized, focusing on its anti-hypotensive, ischemia-reperfusion injury protection, asthma and other active effects, in order to provide reference for the further development and utilization of the volatile oil of Angelicae Sinensis Radix.