Aim To investigate the effect of KHSRP on the malignant biological behavior of gastric cardia ade-nocarcinoma by targeting JAK1/STAT3 signaling axis.Methods The expression levels of KHSRP in adeno-carcinoma tissues of gastric cardia adenocarcinoma and adjacent tissues were collected and compared.qRT-PCR experiment to detect transfection efficiency in gas-tric cardia adenocarcinoma cell lines(OE-19,TE-7,BIC-1,FLO-1,SK-GT-4,BE-3)and normal gastric mucosal epithelial cell line(GES-1).The knockdown and overexpression of KHSRP were treated by packa-ging lentiviral Vector,and the cells were divided into sh-NC group,sh-KHSRP group,vector group,and KH-SRP group.Cell counting kit-8(CCK-8)and Tran-swell assay were used to determine the effects of KH-SRP on the proliferation,migration and invasion of ade-nocarcinoma cells of gastric cardia adenocarcinoma.Xenograft tumor models were used to detect the effects of knockdown and overexpression of KHSRP in live an-imals.WB experiments confirmed that KHSRP targeted the JAK/STAT signaling pathway.Results KHSRP was overexpressed in GCA tissues and cell lines(P＜0.05).Cell function assay analysis showed that KH-SRP overexpression significantly promoted GCA cell proliferation,migration and invasion in vitro(P＜0.05).After KHSRP knockdown,the phosphorylation levels of JAK1 and STAT3 in JAK/STAT signaling pathway were significantly decreased,and the situation was opposite after KHSRP overexpression(P＜0.05).Conclusion KHSRP regulates the malignant progres-sion of metastasis of gastric cardia adenocarcinoma by activating JAK1/STAT3 signaling axis.

Objective To explore the validity and feasibility of the left transthoracic and esophageal hiatal approach for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction under a single position.Methods The clinical data of 64 patients with Siewert type Ⅱ AEG(single position transthoracic approach group)treated with the left transthoracic and esophageal hiatal approach under a single position and 56 patients with the laparoscopic transesophageal slit approach(transabdominal approach group)in the Department of Thoracic Surgery,Huaihe Hospital of Henan University,from January 2017 to December 2018 were retrospectively analyzed.The clinical and pathological data,perioperative indicators(operation time,intraoperative blood loss,postoperative first ambulation time,postoperative first peristalsis time,postoperative drainage volume at 3 d,incidence of postoperative complications,postoperative hospital stay),postoperative complications(positive surgical margin,proximal esophageal resection margin,tumor diameter,total number of dissected lymph nodes,positive lymph node dissection rate,postoperative histopathology,and TNM staging of tumor pathology),and survival indicators(tumor recurrence and metastasis rate and survival at 1 month,3 months,6 months,1 year,3 years,5 years after surgery)were compared between the two groups.Kaplan-Meier method was used to analyze the postoperative survival rate of the two groups.Univariate analysis using χ2 test was employed to analyze factors influencing 5-year postoperative survival rate in Siewert type Ⅱ AEG patients.Results No significant difference was observed in clinical and pathological data,such as gender,age,American Society of Anesthesiologists(ASA)grade,tumor differentiation,pTNM stage,and tumor diameter between the two groups(P>0.05).No significant differences were noted in intraoperative blood loss,incidence of postoperative complications,and survival rates at 1 month,3 months,6 months,1 year,and 3 years after surgery between the two groups(P>0.05).The single position transthoracic approach group exhibited a higher postoperative drainage volume at 3 d compared to the transabdominal approach group(P<0.001),a shorter surgical time(P<0.001),a longer time to first mobilization,first intestinal peristalsis,and hospital stay after surgery(P<0.01),a longer proximal esophageal margin(P<0.001),a higher total number of lymph node dissections(P<0.001),and a higher positive lymph node dissection rate(P<0.05)than the transabdominal approach group.The 5-year recurrence-free survival rate of the single position transthoracic approach group was higher than that of the transabdominal approach group,with a statistically significant difference(P=0.013).The Kaplan-Meier survival curve showed no statistically significant difference in the 5-year overall survival rate between the two groups of patients after surgery(P=0.456).The results of univariate analysis indicated that there are significant relationships between tumor differentiation degree,pTNM stage,tumor diameter,and lymph node positivity rate with the 5-year postoperative survival rate in Siewert type Ⅱ AEG patients(P<0.05).Conclusion Siewert type Ⅱ AEG patients can be treated with the left transthoracic and esophageal hiatal approach under a single position,achieving the same effect as laparoscopic transesophageal slit approach,and it can be actively promoted as a complementary choice of operation in the clinic.

Objective:To evaluate the clinical efficacy of"Shibao Decoction"in the management of late-onset hypogonadism(LOH)caused by deficiency of kidney essence.Methods:Sixty male patients with late-onset hypogonadism of kidney essence defi-ciency type were randomly assigned to the treatment group and the control group,each with 30 cases.The patients in treatment group were treated with oral Shibao Decoction,while the control group was treated with oral Testosterone Undecanoate Capsules.The patients in both groups were treated for 12 weeks.The PADAM symptom score,TCM syndrome score,serum total testosterone(TT),serum free testosterone(FT),sex hormone binding globulin(SHBG),body mass index(BMI),total skeletal muscle mass index(SMI),appendicular skeletal muscle mass index(ASMI),FBG,FINS,and insulin resistance index(HOMA-IR)levels were compared be-tween the two groups.Results:After treatment,PADAM scores for each item and TCM symptoms score decreased,TT and FT in-creased in both groups,all with statistically significant differences from those of pre-treatment(P＜0.05).The level of SHBG in the control group decreased(P＜0.05),which had not changed significantly in the treatment group(P＞0.05).After treatment,SMI and ASMI increased in both groups significantly(P＜0.05).BMI decreased in the control group(P＜0.05),which had not changed significantly in the treatment group(P＞0.05).The level of FINS decreased in the control group(P＜0.05),which had not changed significantly in the treatment group(P＞0.05).FPG had not changed significantly in both groups(P＞0.05),and the insulin resist-ance index(HOMA-IR)had significantly improved in both groups,all with statistically significant differences from those of pre-treat-ment(P＜0.05).After treatment,the total effective rates of PADAM score and TCM syndrome score in the treatment group were 73.3％and 86.6％respectively,and the total effective rates in the control group were 66.7％and 76.6％respectively.The total ef-fective rates of the two scores in the treatment group were slightly higher than those in the control group(P＞0.05).There was no sig-nificant difference in the indicators between the two groups after treatment,and the treatment group is generally comparable with the control group in the therapeutic effects(P＞0.05).And no adverse reactions occurred during treatment in both groups.Conclu-sion:The"Shibao Decoction"has a remarkable therapeutic effect on late-onset hypogonadism caused by deficiency of kidney essence and has good safety.It can be used as an alternative to testosterone undecanoate and is worthy of clinical promotion and application.

Aim To investigate the effect of KHSRP on the malignant biological behavior of gastric cardia ade-nocarcinoma by targeting JAK1/STAT3 signaling axis.Methods The expression levels of KHSRP in adeno-carcinoma tissues of gastric cardia adenocarcinoma and adjacent tissues were collected and compared.qRT-PCR experiment to detect transfection efficiency in gas-tric cardia adenocarcinoma cell lines(OE-19,TE-7,BIC-1,FLO-1,SK-GT-4,BE-3)and normal gastric mucosal epithelial cell line(GES-1).The knockdown and overexpression of KHSRP were treated by packa-ging lentiviral Vector,and the cells were divided into sh-NC group,sh-KHSRP group,vector group,and KH-SRP group.Cell counting kit-8(CCK-8)and Tran-swell assay were used to determine the effects of KH-SRP on the proliferation,migration and invasion of ade-nocarcinoma cells of gastric cardia adenocarcinoma.Xenograft tumor models were used to detect the effects of knockdown and overexpression of KHSRP in live an-imals.WB experiments confirmed that KHSRP targeted the JAK/STAT signaling pathway.Results KHSRP was overexpressed in GCA tissues and cell lines(P＜0.05).Cell function assay analysis showed that KH-SRP overexpression significantly promoted GCA cell proliferation,migration and invasion in vitro(P＜0.05).After KHSRP knockdown,the phosphorylation levels of JAK1 and STAT3 in JAK/STAT signaling pathway were significantly decreased,and the situation was opposite after KHSRP overexpression(P＜0.05).Conclusion KHSRP regulates the malignant progres-sion of metastasis of gastric cardia adenocarcinoma by activating JAK1/STAT3 signaling axis.

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC₅₀ of 30.96 μmol·L^-1, and KBA (30 μmol·L^-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

With the development of digital technology,computer-aided design and manufacturing(CAD/CAM)combined with 3D printing technology is increasingly used in clinical and teaching applications in dentistry.In clinical dentistry,3D printing technology has been widely used in oral and maxillofacial surgery,orthodontics and implantation.Traditional oral laboratory teaching usually uses extracted teeth,resin teeth or various dental models,while 3D printing of oral models can achieve standardized,mass-produced and close-to-real clinical application,which better meets the needs of clinical pre-practice teaching.This article reviews the latest educa-tional applications of 3D printing of dental models in teaching of oral restoration,dental pulp-cavity,oral and maxillofacial surgery,and summarizes the selection of different printing processes and printing materials,aiming to apply the research strategy of 3D printing technology in pre-clinical teaching in dentistry.Finally,the article explores the trends and urgent problems that need to be solved in the development of 3D printed dental models.

Objective To compare the efficacy and safety between hypofractionated radiotherapy(HyRt)and conventional radiotherapy after breast-conserving surgery.Methods This study was a single-center,prospective,randomized controlled study.Eighty-three patients with pTis-T2N0M0 breast cancer admitted to Tangshan People's Hospital from May 2017 to May 2019 were included.The patients received breast-conserving surgery+sentinel lymph node biopsy(SLNB).After surgery,they were treated with intensity modulated radiation therapy(IMRT).According to random table method,patients were divided into HyRt group(n=41)and conventional radiotherapy group(n=42).The dose of organs at risk,treatment efficacy,treatment failure modes,and radiotherapy related adverse reactions were analyzed in the two groups.The radiotherapy-related adverse reactions were evaluated according to NCI CTC AE Version 3.0,including radiation dermatitis,radiation pneumonia,breast/skin fibrosis,pulmonary fibrosis,etc.Results Eighty-three patients with breast cancer were included,with a median age of 44(26-67)years.There was no statistically significant difference in clinical parameters such as age(P=0.443),TNM stage(P=0.335),molecular typing(P=0.333),degree of differentiation(P=0.617),and pathological type(P=0.127)between the two groups of patients.Compared with conventional radiotherapy group,the V5(25.6％vs.33.8％,P=0.015),V20(13.3％vs.17.2％,P=0.042),and the mean radiation dose(MLD;7.4 Gy vs.10.4 Gy,P=0.020)of the affected lung of HyRt group significantly decreased.Only 3 patients in this study experienced distant metastasis,and no regional lymph node metastasis or local recurrence was observed.There was no significant difference in PFS rate at 2 years between HyRt group and conventional radiotherapy group(94.4％vs.85.2％,P=0.818).Compared with conventional radiotherapy group,the incidence of≥grade Ⅱ irradiation dermatitis in HyRt group was significantly reduced(2.4％vs.21.4％,P=0.015).There was no difference in the incidence of grade Ⅰ breast/skin fibrosis(19.5％vs.14.3％,P=0.570)between the two groups,and no grade Ⅲ radiotherapy-related side effects were observed in the two groups.Conclusions Compared with conventional radiotherapy with simultaneously integrated boosting-intensity modulated radiotherapy,the patients who received HyRt after breast-conserving surgery for early-stage breast cancer have good tolerance and low incidence of adverse reactions.HyRt can be used as the first option of radiation therapy.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.