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.

AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

The cold congeal and blood stasis syndrome is a common clinical traditional Chinese medicine（TCM） syndrome. The animal model of cold ongeal and blood stasis syndrome is the basis for exploring the essence of TCM cold congeal and blood stasis syndrome，and the premise of follow-up TCM clinical research.This paper summarized the preparation method， theoretical support，and evaluation method of animal models of cold congeal and blood stasis syndrome in recent years and analysed the strengthens and weaknesses of different models. At present，the common animal models of cold congeal and blood stasis syndrome mainly include etiological model，etiological and pathological composite model and disease-syndrome combination model. The etiological model was mainly prepared by cold exposure，which could be divided into whole-body freezing， ice bath and local frostbite. The etiological and pathological composite model was mainly prepared by cold stimulation combined with epinephrine injection. The common disease-syndrome combination models included the coronary heart disease model of cold congeal and blood stasis syndrome，primary dysmenorrhea model of cold congeal and blood stasis syndrome，endometriosis model of cold congeal and blood stasis syndrome， and arteriosclerosis obliterans model of cold congeal and blood stasis syndrome. The three models have both advantages and disadvantages. Specifically， the disease-syndrome combination model had the highest consistency with clinical practice and was more reliable and practical. However， the disease types of this model were specific，and the combination method of disease and syndrome was controversial. The evaluation indicators of the animal models of cold congeal and blood stasis syndrome focused on the characterization of the syndrome and the physico-chemical indicators related to blood flow，such as blood rheology，coagulation function and microcirculation. In addition， some scholars explored the evaluation indicators from the aspects of vasomotor function，endocrine and energy metabolism. The objectivity and specificity of the current model evaluation methods needed to be further improved. The research of animal model of cold congeal and blood stasis syndrome should be based on clinical practice and oriented by clinical demand. Only by establishing animal models that are highly consistent with the characteristics of clinical disease and syndrome can we better reveal the essence of cold congeal and blood stasis syndrome and promote the modernization of TCM.

Consensus ; Critical Illness ; Humans ; Serum Albumin ; Serum Albumin, Human

Objective:To explore the macroscopic medication rule of Chinese medicine for the treatment of primary liver cancer and provide references for clinical medication. Method:The databases of CNKI，VIP， and Wanfang Data were searched for research articles published from September 1959 to June 2019 with the terms of "Chinese medicine" and "liver cancer". A database was established based on the collected Chinese medicinal prescriptions for the treatment of primary liver cancer. The frequency，clustering， and association rules were analyzed by Excel， etc. Result:In this study，106 effective articles were included，and after the modified prescriptions were removed， 92 effective prescriptions were screened out，involving 281 Chinese herbal medicines used for 1 181 times in total. The top 5 high-frequency drugs were Poria （deficiency-tonifying），Astragali Radix （heat-clearing），Bupleuri Radix （blood-activating and stasis-resolving），Paeoniae Radix Alba （urination-promoting and dampness-draining）， and Codonopsis Radix （Qi-regulating）. The analysis of drug flavor with a frequency higher than 10 showed that most of the drugs were sweet，bitter， and pungent in flavor，cold，warm， and plain in nature，and acted on spleen and liver meridians. Four combinations and 10 herbal pairs were obtained by the cluster analysis of high-frequency drugs and association analysis， respectively. The high-frequency drugs and potential herbal pairs were classified targeting the specific clinical syndromes in different stages of liver cancer. Conclusion:Replenishing Qi， invigorating spleen，clearing heat， removing toxin，activating blood， and resolving stasis were the basic principles for the treatment of primary liver cancer. The combination of those drugs was the main therapeutic strategy. In addition，the resulting 10 potential herbal pairs from high-frequency drugs and cluster analysis could inspire the clinical treatment of primary liver cancer in different clinical stages with various clinical syndromes， which was of reference value for the clinical medication.

Objective:To analyze the clinical characteristics of gastrointestinal symptoms and liver function injury in patients with coronavirus disease 2019 (COVID-19).Methods:From January 23, 2020 to February 29, 2020, the medical records of 251 patients with COVID-19 admitted to the West Campus of the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, were collected. The proportion of the patients with gastrointestinal symptoms including anorexia, nausea and vomiting, diarrhea and abdominal pain were analyzed respectively. The patients were divided into common type (76 cases), severe type (65 cases) and critical type (110 cases). The incidence of liver function injury and the changes of liver function parameters such as total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), albumin and globulin of the patients with different clinical types and with or without gastrointestinal symptoms were analyzed. Mann-Whitney U test, Chi square test and Fisher′s exact test were used for statistical analysis. Results:The main gastrointestinal symptoms of patients with COVID-19 were anorexia (33.9%, 85/251), diarrhea (12.0%, 30/251), nausea and vomiting (7.6%, 19/251) and abdominal pain (1.2%, 3/251). 143 patients (57.0%) had liver function injury, the rate of liver function injury in critical type patients was 75.5% (83/110), which was higher than that of common type patients (40.8%, 31/76) and severe type patients (44.6%, 29/65), and the differences were statistically significant ( χ2=22.765 and 16.865, both P<0.01). There was no significant difference in the proportion of patients with liver function injury between common type and severe type patients ( P>0.05). There was no statistically significant difference in the proportion of liver function injury between patients with gastrointestinal symptoms and those without gastrointestinal symptoms (57.8%(67/116) vs. 56.3%(76/135), P>0.05). The median values of TBil, DBil, ALT, AST, ALP, GGT, LDH and globulin level of critical type patients were 13.5 μmol/L, 4.9 μmol/L, 44.5 U/L, 50.0 U/L, 64.0 U/L, 41.0 U/L, 527.0 U/L and 33.6 g/L respectively. The proportions of critical type patients with TBil level >34.2 μmol/L, DBil level>13.6 μmol/L, ALT level>80 U/L and AST level>80 U/L were 7.3% (8/110), 7.3% (8/110), 17.3% (19/110) and 17.3% (19/110), respectively. These results were all higher than those of common type patients (9.5 μmol/L, 2.9 μmol/L, 28.5 U/L, 28.5 U/L, 54.0 U/L, 25.5 U/L, 225.5 U/L, 30.1 g/L, 0, 0, 6.6% (5/76) and 2.6% (2/76) ) and severe type patients (10.4 μmol/L, 3.4 μmol/L, 30.0 U/L, 31.0 U/L, 49.0 U/L, 25.0 U/L, 284.0 U/L, 30.7 g/L, 0, 0, 6.2% (4/65) and 1.5% (1/65)), and the differences were statistically significant ( Z=-4.264, -5.507, -4.000, -6.558, -3.112, -4.333, -4.858, -3.873, Fisher′s exact test, Fisher′s exact test, χ2=4.574, 9.620; Z=-3.060, -3.850, -3.923, -5.005, -9.495, -7.651, -3.853, -2.725, Fisher′s exact test, Fisher′s exact test, χ2=4.425, 10.169; all P<0.01). The median values of pre-albumin level, albumin level and the albumin to globulin ratio of critical type patients were 85.3 g/L, 28.2 g/L and 0.8, which were all lower than those of common type patients (157.3 g/L, 32.3 g/L and 1.1, respectively) and severe type patients (133.6 g/L, 31.6 g/L and 1.1, respectively), and the differences were statistically significant ( Z=-6.631, -3.647, -4.924, -4.503, -5.283 and -3.903, all P<0.01). The median albumin level of patients with diarrhea was lower than that of patients without diarrhea (28.2 g/L vs. 30.5 g/L), the proportion of diarrhea patients whose TBil level >20.0 to 34.2 μmol/L was higher than that of patients without diarrhea (70.0%, 21/30 vs. 10.9%, 24/221), and the differences were statistically significant ( Z=-2.182, χ2 =62.788; both P<0.05). Conclusions:Anorexia is the most common digestive symptom in COVID-19 patients, and the incidences of abdominal pain is low. The incidence of liver function injury of critical type patients is high. There is no significant correlation between gastrointestinal symptoms and liver function injury, and patients with diarrhea have lower albumin levels.

OBJECTIVE: To identify the role of Tribbles pseudokinase 3 (TRIB3) during the process of adipogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs), and to provide a new target and a novel idea for the application of hASCs in adipose tissue engineering and soft tissue regeneration. METHODS: TRIB3-knockdown hASCs (shTRIB3) and TRIB3-overexpression hASCs (TRIB3-over) were established using lentivirus transfection technique. The transfection effect was estimated by the visible presence of green fluorescence as the expression of green fluorescent protein (GFP) in the transfected hASCs. The lentiviral transfection efficiency was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. After adipogenic induction, Oil Red staining and quantification, as well as qRT-PCR about several specific adipogenic markers were used to evaluate the adipogenic differentiation ability of hASCs. RESULTS: In TRIB3-knockdown hASCs, the TRIB3 mRNA expression level decreased by about 84.3% compared with the control group (P<0.01), and the TRIB3 protein level also showed obvious reduction. Oppositely, in TRIB3-overexpression hASCs, the TRIB3 mRNA expression level increased by approximately 160% compared with the control group (P<0.01), and the TRIB3 protein level also showed a significant increase. These results indicated a successful construction of TRIB3-knockdown hASCs and TRIB3-overexpression hASCs. The Oil Red staining results showed that the down-regulation of TRIB3 significantly promoted lipid droplets formation in hASCs, consistent with Oil Red quantification. On the other hand, the up-regulation of TRIB3 suppressed lipid droplets formation in hASCs, consistent with Oil Red quantification. After adipogenic induction, adipogenesis-related genes, including peroxisome proliferator-activated receptor γ (PPARγ), cluster of differentiation 36 (CD36) and CCAAT/enhancer binding protein α (C/EBPα), were increased significantly in TRIB3-knockdown hASCs compared with the control group (P<0.01). Oppositely, PPARγ, CD36 and lipoprotein lipase (LPL) were significantly decreased in TRIB3-overexpression hASCs compared with the control group (P<0.01). CONCLUSION TRIB3 inhibited the adipogenic differentiation of hASCs. Knockdown of TRIB3 promoted the ability of adipogenesis of hASCs, while overexpression of TRIB3 inhibited the adipogenic differentiation of hASCs. Considering the important role of PPARγ in the adipogenis process, the molecular mechanism of the regulatory function of TRIB3 may be related with PPARγ signal pathway.
Adipogenesis ; Adipose Tissue ; Cells, Cultured ; Humans ; Mesenchymal Stem Cells

Pepino mosaic virus (PepMV) causes severe disease in tomato and other Solanaceous crops around globe. To effectively study and manage this viral disease, researchers need new, sensitive, and high-throughput approaches for viral detection. In this study, we purified PepMV particles from the infected Nicotiana benthamiana plants and used virions to immunize BALB/c mice to prepare hybridomas secreting anti-PepMV monoclonal antibodies (mAbs). A panel of highly specific and sensitive murine mAbs (15B2, 8H6, 23D11, 20D9, 3A6, and 8E3) could be produced through cell fusion, antibody selection, and cell cloning. Using the mAbs as the detection antibodies, we established double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), Dot-ELISA, and Tissue print-ELISA for detecting PepMV infection in tomato plants. Resulting data on sensitivity analysis assays showed that both DAS-ELISA and Dot-ELISA can efficiently monitor the virus in PepMV-infected tissue crude extracts when diluted at 1:1 310 720 and 1:20 480 (weight/volume ratio (w/v), g/mL), respectively. Among the three methods developed, the Tissue print-ELISA was found to be the most practical detection technique. Survey results from field samples by the established serological approaches were verified by reverse transcription polymerase chain reaction (RT-PCR) and DNA sequencing, demonstrating all three serological methods are reliable and effective for monitoring PepMV. Anti-PepMV mAbs and the newly developed DAS-ELISA, Dot-ELISA, and Tissue print-ELISA can benefit PepMV detection and field epidemiological study, and management of this viral disease, which is already widespread in tomato plants in Yunnan Province of China.
Animals ; Antibodies, Monoclonal/immunology* ; China ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay/methods* ; Female ; Hybridomas ; Solanum lycopersicum/virology* ; Mice ; Mice, Inbred BALB C ; Plant Diseases/virology* ; Potexvirus/metabolism* ; Sensitivity and Specificity ; Nicotiana

Objective To investigate the safety and effectiveness of vacuum sealing drainage treatment on limb salvage in multiple trauma patients combined with Gustilo type ⅢC fracture.Methods A retrospective case control study was conducted to analyze the clinical data of 102 patients diagnosed with multiple trauma combined with Gustilo type Ⅲ C fracture admitted to Tongji Hospital from October 2005 to October 2015.There were 66 males and 36 temales,aged 17-65 years [(34.2 10.1) years].The injury severity score (ISS) ranged from 18 to 26 points [(19.8 ± 3.2)points].There were 34 patients with femur fracture,66 with tibia/fibula fracture,35 with femur and tibia/fibula fracture.Among the patients,58 were treated with VSD (VSD group) and 44 were treated with routine dressing change after emergency operation (routine group).The two groups were compared for active bleeding,re-vascular exploration,osteofascial compartment syndrome,wound infection and necrosis,gas gangrene,delayed amputation,systemic inflammatory response syndrome (SIRS),sepsis,deep venous thrombosis (DVT)incidence,per capita debridement times,length of stay,skin graft/skin flap rate,fracture fixation rate,incidence of refractory wounds,incidence of nonunion,incidence of complete nerve damage,British medical research council (BMRC) score,and amputation rate/salvage rate.Results All patients were followed up for 6-14 months [(8.4.2.1) months].There was no significant difference in limb salvage rate between the two groups after operation (P ＞ 0.05).Among the indexes of limb salvage treatment after operation,no significant differences were found between the routine group and VSD group in active bleeding,gas gangrene,re-vascular exploration and delayed amputation (P ＞ 0.05);the wound infection and necrosis rates were 32％ and 15％ (P ＜ 0.05);the incidence rates of osteofascial compartment syndrome were 22％ and 7％ (P ＜ 0.05).During the hospital stay,there were no significant differences in DVT incidence and fracture internal fixation rate between the two groups;SIRS incidence rates of routine group and VSD group were 92％ and 73％ (P ＜0.05);the incidence rates of sepsis were 28％ and 10％ (P ＜ 0.05);the per capita debridement times in routine group and VSD group were 4.2 times and 3.2 times,respectively (P ＜ 0.05);hospitalization durations were 42.1 days and 30.2 days (P ＜0.05);skin graft/skin flap rates were 69％ and 46％ (P ＜ 0.05).In the follow-up results,there was no significant difference in the amputation rate/salvage rate between the two groups (P ＜ 0.05).The incidence of refractory wounds was 28％ in routine group and 10％ in VSD group (P ＜ 0.05);the incidence of nonunion was 22％ and 6％ (P ＜ 0.05);the incidence of complete neurological damage was 36％ and 12％ (P ＜ 0.05);the excellent and good rate of BMRC score was 83％ and 96％ (P ＜ 0.05).Conclusions VSD technology can promote wound healing after operation,prevent complications,reduce the number of debridement operations and shorten hospital stay,significantly improving the prognosis and limb function of patients.It is a relatively safe and effective method for the treatment of multiple trauma combined with Gustilo type Ⅲ C fracture.