Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Brain metastasis is a common complication of non-small cell lung cancer (NSCLC) patients. About 25%-55% of patients with NSCLC will develop brain metastases, and the occurrence of brain metastasis predicts a poor prognosis. Traditionally, radiotherapy, chemotherapy, targeted therapy and surgery are the main treatment options for NSCLC patients with brain metastases. In recent years, with the emergence of immune checkpoint inhibitors (ICI), the survival of NSCLC patients with brain metastases has been significantly improved. This article reviews the research progress of ICI treatment for NSCLC patients with brain metastases in order to provide new treatment strategies.

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.
Acid Sensing Ion Channels/physiology* ; Animals ; HEK293 Cells ; Humans ; Pressoreceptors/physiology* ; Rats ; TRPV Cation Channels/physiology*

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch–aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch–aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.

Objective： ：To study the regulatory effect of mogrol (MO) on lipid metabolism of hepatic cancer cells and its molecular mechanism. Methods: Oleic acid (OA) was used to induce fat accumulation in hepatocellular carcinoma HepG2 cells and to establish a steatosis cell model. CCK-8 method was used to detect the cytotoxicity of MO to HepG2 cells, and an experimental working concentration without obvious cytotoxicity of MO was chosen. After being treated with different concentrations of MO, lipid accumulation in the cells was observed by oil red O staining, and the contents of triglyceride (TG) and cholesterol (TC) in the cells were measured. Key genes involving in lipid metabolism were screened out by high-throughput transcriptome sequencing qPCR was used to detect the mRNA expressions of ,SREBP-1c and FASN, while Western Blot was used to detect the protein expressions of p-AMPKα, SREBP-1c and FASN in cells of model group and treatment group. Results: After OA induction, a large amount of lipids accumulated in HepG2 cells, the contents of TG and TC increased significantly. Three key genes (SREBP-1c, FASN and p-AMPK α) involving in lipid metabolism of hepatic cancer cells were screened out. After OA induction, the mRNA expressions of SREBP-1c and FASN increased, the protein expression of p-AMPK α decreased while the protein expressions of SREBP-1c, FASN and other proteins increased significantly. After intervention with working concentration of MO, intracellular lipid accumulation, contents of TG and TC, mRNA expressions of SREBP-1c, FASN and protein expressions of SREBP-1c, FASN decreased significantly, while the expression of p-AMPKα increased. Conclusion: Mogrol can inhibit the synthesis of fatty acids by activating the expression level of AMPK signaling pathway related factors SREBP-1c and FASN, so as to play the role of regulating lipid metabolism.

Objective To investigate the relationship between programmed death receptor ligand 1 (PD-L1) and regulatory T cell(Treg) in non-small cell lung cancer.Methods Seventy-nine patients with non-small cell lung cancer who were treated in Hainan Provincial People's Hospital from December 2013 to December 2015 were selected.The levels of PD-L1 and Treg in cancer tissues and adjacent tissues were detected,observed the relationship with clinical pathological features,and analyzed the correlation of PD-L1 level and Treg infiltration.Results High expression of PD-L1 (53.2％,42/79) and Treg (50.6％,40/79) in cancer tissues were significantly higher than those in adjacent tissues (3.8％ (3/79),5.1％ (4/79)),the difference was significant (x2 =9.761,9.002,P＜0.05).High expression of PD-L1 (87.5％,28/32) and Treg(84.4％,27/32)were significantly higher in stage]Ⅲ and Ⅳ cancer tissues than those in stage Ⅰ and Ⅱ cancer tissues(29.8％(14/47),27.7％ (13/47)),the difference was significant (x2 =8.958,7.274,P ＜ 0.05).High expression of PD-L1 (85.3％,29/34) and Treg (88.2％,30/34) were significantly higher in lymph node metastasis cancer tissues than those in non-lymph node metastasis cancer tissues (28.9％ (13/45),22.2％ (10/45)),the difference was significant(x2=8.146,9.056,P＜0.05).The high level of PD-L1 in cancer tissues was positively correlated with high Treg infiltration (r =0.762,P＜0.05).Conclusion The expression of PD-L1 and Treg in non-small cell lung cancer tissues is related to the lymph node metastasis and stage,and the high expression of PD-L1 is positively correlated with the high infiltration of Treg.

Objective To explore the clinical features of sentinel polyps (rectal polyps with proximal colon carcinoma), and the correlation between sentinel polyps and proximal colon carcinoma. Methods The clinical data of 331 patients with rectal polyps were retrospectively analyzed. According to the combination condition of proximal colon carcinoma, the patients were divided into sentinel polyps group (observation group, 37 cases) and pure rectal polyps group (control group, 294 cases). The family history, laboratory examination, colonoscopy, clinical pathological features, treatment, sequelae and short-term prognosis were compared between 2 groups. Results The family history rate, positive rate of tumor marker and the incidences of polyps maximum diameter>1 cm, polyps>5 pieces, adenomatous polyp in observation group were significantly higher than those in control group:35.1%(13/37) vs. 4.8%(14/294), 67.6%(25/37) vs. 6.8%(20/294), 62.2%(23/37) vs. 46.6%(137/294), 43.2%(16/37) vs. 11.9%(35/294) and 83.8%(31/37) vs. 35.4%(104/294), and there were statistical differences (P<0.01). The patients in control group did not have special find in colonoscopy. The majority patients in observation group had new organisms around the lumen growth in colonoscopy, but the intestinal canal between rectal polyps and proximal colon carcinoma did not have special find. The majority pathologic type of proximal colon carcinoma patients in observation group was papillary adenoearcinoma and tubular adenocarcinoma, 75.7%(28/37). Duke stage:A stage was in 11 cases (29.7%, 11/37), B stage in 11 cases (29.7%, 11/37), C stage in 9 cases (24.3%, 9/37), and D stage in 6 cases (16.2%, 6/37). In control group, 282 patients (95.9%, 282/294) were treated by endoscope, and they were cured and discharged. In observation group, 15 patients (40.5%, 15/37) were treated with radical operation, 9 patients (24.3%, 9/37) by endoscope, 7 patients (18.9%, 7/37) with palliative surgery, 4 patients (10.8%, 4/37) with chemotherapy, and 2 patients (5.4%, 2/37) with symptomatic treatment;the patients were followed up for 6-12 months, the 23 patients with complete tumor resection did not relapse, 12 patients showed tumor reduction or symptomatic relief, and the other 2 patients died. Conclusions If maximum diameter over 1 cm, multiple and adenomatous polyps exist, the possibility of carcinogenesis of the polyps or the proximal colon should be awared. The patients should be followed up in short-term and complete the whole colon examination.

This study was aimed to investigate the induction effect ofRe-Du-Ning (RDN) Injection on rat liver microsome CYP450 enzymes. SD rats were randomly divided into the solvent control group, positive control group as well as the low, middle and high dose group of RDN (1, 2, 4 mL·kg-1·d-1). After drugs were administrated continuously for 7 days, the rats were sacrificed. The liver was weighed and prepared to microsomes. Meanwhile, the liver coefficients of rats were calculated. And the protein content was detected by BCA method. Finally, activities of five important subtypes of CYP450 enzymes such as CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A1/2 were measured by the“cocktail” method. The results showed that the levels of liver coefficients, microsome yield rate and activities of CYP450 subtypes increased significantly in the positive control group compared with the solvent control group (P < 0.01). There was no significant difference on the levels of liver coefficients, microsome yield and protein content between the low and middle dose group of RDN. However, there was significant difference on the levels of liver coefficients and microsome yield in the high dose group (P < 0.05). In terms of the influence on enzyme activity, RDN Injection can significantly induce the activities of CYP1A2 with dose dependence. It can induce the activities of CYP2C9 and CYP2C19 at the middle and high dose. However, there was no obvious influence on the activities of CYP3A1/2 and CYP2D6. It was concluded that the positive control group can obviously induce activities of CYP450, which can be used in the evaluation of induction experiments. RDN Injection had induction effect on CYP1A2, CYP2C9 and CYP2C19. But it had no influence on the activities of CYP3A1/2 and CYP2D6.

This paper was aimed to study the human plasma protein binding rate of diterpene ginkgolides meglumine injection.The equilibrium dialysis was used to determine the human plasma protein binding rate of ginkgolide A (GA),ginkgolide B (GB) and ginkgolide K (GK) in diterpene ginkgolides meglumine injection.The LC-MS/MS method was used for the content determination of ginkgolides.And then,the plasma protein binding rate was calculated.The results showed that there was no interference from other ingredients for the determination of ginkgolides.The calibration curve of the analytes was in good linearity in certain range of contents.The precision and stability of the analytes met the methodology requirements.After 8 h incubation,the human plasma protein binding rate of GA,GB and GK achieved balance.The human plasma protein binding rate of GA (0.34,1.70 and 8.51μg·mL-1) was 84.03%-88.11%; the human plasma protein binding rate of GB (0.62,3.09 and 15.5μg·mL-1) was 41.21%-53.56%; the human plasma protein binding rate of GK (0.04,0.20 and 1.01μg·mL-1) was 45.24%-59.59%.It was concluded that the method was simple,rapid and sensitive,which met the analysis requirement for biological samples.GA had a high plasma protein binding rate; GB and GK had medium plasma protein binding rate.

Objective This study aimed to develop reading material for nasalance evaluation ,and find out na-salance scores associated with genders .Methods The NasalView ? (Tiger Electronics Inc .,Seattle ,USA) was used to obtain nasalance values in the new and old material .A total of 102 subjects (51 males ,51 females) who have lived in Beijing for 18 years or longer at the time of the experiment received the tests ,the results from two pieces of material and the mean nasalance gender score differences were compared .Results The mean nasalance scores of sen-tences were 56 .58% ± 3 .43% for'Nasal sentence',33 .86% ± 5 .24% for'Oral sentence',and 49 .49% ± 4 .13% for'Oro -nasal sentence'respectively in the new material .The mean nasalance scores of sentences were 54 .31% ± 4 .43% for'Nasal sentence',35 .64% ± 5 .90% for'Oral sentence',and 47 .12% ± 4 .96% for'Oro-nasal sentence're-spectively in the old material .There were significant differences between males and females through materials .The nasalance gender score differences showed that females were bigger than males (P<0 .01) .This study found a cor-relation between the new and old materials :'Nasal sentence'(r=0 .899 ,P< 0 .01) ,'Oral sentence'(r= 0 .850 ,P<0 .01) ,and'Oro -nasal sentence'(r=0 .851 ,P<0 .01) .The standard error difference showed that the new was smaller than the old (P<0 .01) .Conclusion The new material for nasalance evaluation has a better test validity ,and there is a high correlation between the old materials .The usage of the new material for nasalance evaluation will produce more accurate results with higher credibility .Normal female's nasalance scores were higher than males .