OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

Background and purpose:The resistance of pancreatic cancer to albumin-bound paclitaxel affects the therapeutic effect and prognosis.Signal transducer and activator of transcription 3(STAT3)is one of the important molecules regulating the chemotherapy sensitivity of cancer cells.The liposome BP1003 targeting the antisense oligonucleotide of STAT3 mRNA can inhibit the expression of STAT3 and increase the chemotherapy sensitivity.However,the effect of BP1003 on the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel remains unclear.The purpose of this study was to investigate the effects of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3.Methods:Pancreatic cancer cell lines PANC-1 and ASPC-1 were cultured.They were divided into control group(without drugs),BP1003 group(200 μg/mL BP1003 intervention),different concentrations of albumin-bound paclitaxel group(5,10,20 nmol/L albumin-bound paclitaxel intervention),BP1003+different concentrations of albumin-bound paclitaxel group(200 μg/mL BP1003 combined with 5,10,20 nmol/L albumin-bound paclitaxel intervention).The proliferation viability,apoptotic rate and the protein expression levels of STAT3,STAT4,STAT6,Bcl-2,Bax and c-Myc were detected.The transplanted tumor model was established by subcutaneous injection of PANC-1 and ASPC-1 cell suspension in nude mice,which were divided into control group(normal saline intervention),BP1003 group(25 mg/kg BP1003 intervention,once every 2 weeks)and albumin-bound paclitaxel group(10 mg/kg albumin-bound paclitaxel,once a week),BP1003+albumin-bound paclitaxel group(25 mg/kg BP1003 intervention,once every 2 weeks combined with 10 mg/kg albumin-bound paclitaxel,once a week).Four weeks later,the graft volume and mass were measured,and the protein expression levels of STAT3,Bcl-2,Bax and c-Myc were detected.Results:The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003 group and albumin-bound paclitaxel group were higher than those in the control group,while the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in control group(P＜0.05).There was no significant difference in the expression levels of STAT4 and STAT6 in PANC-1 and ASPC-1 cells between BP1003 group and the control group(P＞0.05).The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003+different concentrations of albumin-bound paclitaxel groups were higher than those in different concentrations of albumin-bound paclitaxel groups,and the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in different concentrations of albumin-bound paclitaxel groups(P＜0.05).The volume and mass of transplanted tumor and the protein expression levels of STAT3,Bcl-2 and c-Myc of nude mice in BP1003 group,albumin-bound paclitaxel group and BP1003+albumin-bound paclitaxel group were all lower compared with the control group,the protein expression level of Bax was higher compared with the control group(P＜0.05),and the above changes in BP1003+albumin-bound paclitaxel group were more significant compared with BP1003 and albumin-bound paclitaxel group.Conclusion:BP1003 increases the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel by inhibiting the expression of STAT3.

Background and purpose:The resistance of pancreatic cancer to albumin-bound paclitaxel affects the therapeutic effect and prognosis.Signal transducer and activator of transcription 3(STAT3)is one of the important molecules regulating the chemotherapy sensitivity of cancer cells.The liposome BP1003 targeting the antisense oligonucleotide of STAT3 mRNA can inhibit the expression of STAT3 and increase the chemotherapy sensitivity.However,the effect of BP1003 on the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel remains unclear.The purpose of this study was to investigate the effects of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3.Methods:Pancreatic cancer cell lines PANC-1 and ASPC-1 were cultured.They were divided into control group(without drugs),BP1003 group(200 μg/mL BP1003 intervention),different concentrations of albumin-bound paclitaxel group(5,10,20 nmol/L albumin-bound paclitaxel intervention),BP1003+different concentrations of albumin-bound paclitaxel group(200 μg/mL BP1003 combined with 5,10,20 nmol/L albumin-bound paclitaxel intervention).The proliferation viability,apoptotic rate and the protein expression levels of STAT3,STAT4,STAT6,Bcl-2,Bax and c-Myc were detected.The transplanted tumor model was established by subcutaneous injection of PANC-1 and ASPC-1 cell suspension in nude mice,which were divided into control group(normal saline intervention),BP1003 group(25 mg/kg BP1003 intervention,once every 2 weeks)and albumin-bound paclitaxel group(10 mg/kg albumin-bound paclitaxel,once a week),BP1003+albumin-bound paclitaxel group(25 mg/kg BP1003 intervention,once every 2 weeks combined with 10 mg/kg albumin-bound paclitaxel,once a week).Four weeks later,the graft volume and mass were measured,and the protein expression levels of STAT3,Bcl-2,Bax and c-Myc were detected.Results:The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003 group and albumin-bound paclitaxel group were higher than those in the control group,while the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in control group(P＜0.05).There was no significant difference in the expression levels of STAT4 and STAT6 in PANC-1 and ASPC-1 cells between BP1003 group and the control group(P＞0.05).The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003+different concentrations of albumin-bound paclitaxel groups were higher than those in different concentrations of albumin-bound paclitaxel groups,and the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in different concentrations of albumin-bound paclitaxel groups(P＜0.05).The volume and mass of transplanted tumor and the protein expression levels of STAT3,Bcl-2 and c-Myc of nude mice in BP1003 group,albumin-bound paclitaxel group and BP1003+albumin-bound paclitaxel group were all lower compared with the control group,the protein expression level of Bax was higher compared with the control group(P＜0.05),and the above changes in BP1003+albumin-bound paclitaxel group were more significant compared with BP1003 and albumin-bound paclitaxel group.Conclusion:BP1003 increases the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel by inhibiting the expression of STAT3.

AIM: To explore the current status, research hotspots, and trends of global uveitis research to provide a theoretical basis and references for researchers in the field of uveitis, and promote further development in this area.METHODS: Relevant literatures on uveitis were retrieved from the China National Knowledge Infrastructure(CNKI)database, Wanfang database, and Web of Science core collection database since their establishment until 24 August 2023. The country/publishing institutions, research authors, high-frequency keywords, and burst keywords were visual analyzed by using software such as GraphPad Prism 9, CiteSpace 6.2. R2, and VOSviewer.RESULTS: Research teams for uveitis have been formed in various countries globally. The top three countries in terms of publications are the United States of America(7 585 papers), the United Kingdom(2 412 papers)and Germany(1 679 papers). The top three foreign institutions in terms of publications are Harvard University, Oregon Health & Science University, and Moorfields Eye Hospital, while the top three domestic institutions are Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Chongqing Medical University, and Zhongshan Ophthalmic Center, Sun Yat-sen University. The analysis of high-frequency keywords and burst keywords in Chinese and English shows that research hotspots mainly focus on exploring pathogenesis and different treatment methods for uveitis. The research hotspots related to uveitis treatment are transitioning to molecular biology-related research topics, such as molecular biological signaling pathways(NF-κB signaling pathway with a strength value of 22.89), biological agents(adalimumab with a strength value of 32.21), and tumor necrosis factor(with a strength value of 48.44). Related research is also expanding to basic experiments on relevant rats.CONCLUSIONS: In recent years, the research hotspots and trends of global uveitis mainly focus on precise diagnosis, pathogenesis, and more effective treatment methods. It is important for more scholars to dedicate themselves to uveitis-related research in the future to make breakthroughs and progress in the field. More large-scale and multicenter clinical studies on uveitis can provide high-quality research evidence.

Objective To explore the effect of endoscopic hemostasis combined with octreotide on hemodynamics and clinical outcome of patients with acute upper gastrointestinal bleeding.Methods From January 2019 to June 2022,80 patients with acute upper gastrointestinal bleeding in Xinyu Yinhe Hospital of Jiangxi Province,and according to random number table method,40 cases each in the control group and 40 cases in the observation group.The control group was treated with conventional endoscopic,while the observation group was treated with octreotide on this basis.The clinical efficacy,high sensitivity C-reactive protein(hs-CRP),cortisol(Cor)levels and hemodynamic changes[cardiac output(CO),heart rate(HR),mean arterial pressure(MAP)]were compared between the two groups.Results The total effective rate of the observation group was significantly higher(P<0.05).After treatment,hs-CRP and Cor levels in 2 groups were lower than before,and hs-CRP and Cor levels in observation group were significantly lower(P<0.05).After treatment,the levels of CO,HR and MAP in the two groups were decreased,and the levels of CO,HR and MAP in the observation group were significantly lower(P<0.05).Conclusion Endoscopic hemostasis combined with octreotide can promote the hemodynamic indexes of patients with acute upper gastrointestinal bleeding to return to normal,improve the levels of hs-CRP and Cor,and improve clinical efficacy.

OBJECTIVES: To establish a system for control of cross-infection and workflow for preventing severe acute respiratory syndrome coronavirus 2 spread and ensuring the safety of medical staffs and patients in endoscopy center during the pandemic of the coronavirus disease 2019 (COVID-19). METHODS: Based on the national publication of relevant documents and relevant guidance of Digestive Endoscopy Branch of Chinese Medical Association, we explored and optimized the workflow, staff protection and sterilization of endoscope in digestive endoscopy center during the pandemic of the COVID-19. RESULTS: The prevention system of cross-infection and workflow in endoscopy during the pandemic of the COVID-19 were developed. The optimized workflow in endoscopy was conducted in 106 patients with necessary endoscopy from the Department of Gastroenterology, Third Xiangya Hospital, Central South University between January 24, 2020 and February 26, 2020, and no case of cross-infection was presented among the medical staffs, patients and family members. CONCLUSIONS Measures on control of cross-infection and workflow in digestive endoscopy center during the pandemic of the COVID-19 are effective, which are beneficial to preventing cross-infection in hospital and provide a scientific guidance for the general work in the digestive endoscopy centers during the pandemic of the COVID-19.
Betacoronavirus ; China ; Coronavirus Infections ; epidemiology ; prevention & control ; Cross Infection ; prevention & control ; Endoscopy ; Gastroenterology ; organization & administration ; Humans ; Pandemics ; prevention & control ; Pneumonia, Viral ; epidemiology ; prevention & control ; Workflow

OBJECTIVE: To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies. METHODS: A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks. RESULTS: A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χ=11.345, χ=10.160, χ=6.358; all < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ=6.813, =0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation. CONCLUSIONS Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.
Antiviral Agents ; Carcinoma, Hepatocellular ; etiology ; DNA, Viral ; Follow-Up Studies ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; complications ; Liver Neoplasms ; etiology ; Prospective Studies

OBJECTIVETo investigate the expression of long noncoding RNA linc00261 in hepatocellular carcinoma (HCC) and its correlation with the clinicopathological features and postoperative outcomes of the patients.

METHODSReal-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of linc00261 in surgical specimens of HCC and adjacent tissues from 74 patients. The correlation of the expression level of linc00261 in HCC with the clinicopathological parameters of the patients was analyzed using Chi-square test. The Cox's proportional hazards regression model was used to assess the value of linc00261 in predicting the prognosis of HCC patients after operation. The expression of linc00261 was also examined in 5 HCC cell lines using qRT-PCR. The HCC cell lines MHCC-LM3 and SNU-449 were transfected with small interfering RNAs targeting linc00261 for linc00261 knockdown, and the changes in the cell proliferation, migration and invasion abilities were observed using CCK-8 assay and Transwell assay.

RESULTSThe expression level of linc00261 in HCC was significantly correlated with AFP (=0.032), tumor size (=0.007), microscopic vascular invasion (MVI; =0.01), and TNM stage (=002). The patients with lowered expressions of linc00261 in HCC tissues had a significantly shortened tumor-free survival time ( < 0.05), and a lowered expression of linc00261 was identified as an independent risk factor affecting postoperative recurrence-free survival time of the patients ( < 0.05). In HCC cell lines MHCC-LM3 and SNU-449 cells, linc00261 knockdown obviously promoted the cell migration and invasion ( < 0.01) but did not significantly affect cell proliferation ( > 0.05).

CONCLUSIONSLinc00261 may serve as a new prognostic biomarker for predicting the postoperative outcomes of the patients with HCC.

Objective To analyze the death status of children ≤ 5 years old in Jiaxing City from 2013 to 2017,and to provide scientific and effective measures of decreasing the children mortality and ensuring the health of children.Methods Death surveillance data of children ≤5 years old was obtained from monitoring network covering the whole city of maternal and child health information systems and the relevant maternal and child health statistics.The mortality rate,the sequence and changing trend of main death causes,prenatal health services of children ≤5 years old in Jiaxing City from 2013 to 2017were analyzed.Results From 2013 to 2017,there were 2 788 cases death of children ≤5 years old in Jiaxing City.The neonatal mortality rate (NMR),infant mortality rate (IMR),≤5 years old children mortality rate(U5MR) in Jiaxing City were 2.33‰,3.52‰ and 4.83 ‰,respectively.The mortality rates of all ages showed a declining trend year by year (x2NMR =19.641,P＜0.001;x2IMR =31.705,P ＜0.001;x2U5MR =48.294,P ＜0.001).There were significant differences in the mortality between the lower local and the migrant children (x22013 =26.16,x22014 =18.45,x22015 =27.72,x22016 =14.49,x22017=24.19;P＜0.001).The top two causes of death in children ≤ 5 years old were drowning,premature birth and low birth weight.The top two causes of death in infants and newborns were premature birth,low birth weight and other congenital anomalies.In the recent five years,49.60％ of children ≤5 years old died in the hospital.At the same time,the proportion of deaths on the way and at home was 15.64％ and 34.76％ respectively.Although there was a gap in the level of prenatal health services between local and mobile children,the gap has been declining year by year.Conclusions The key measures to decrease the mortality rate of children under 5 years old in Jiaxing City include strengthening the management of pregnancy care and high-risk pregnancy;paying attention to tertiary prevention and doing a good job in monitoring birth defects such as prenatal screening;enhancing safety education and child supervision for parents of children in 1-4 years old;reinforcing the construction of maternal and child health professional team and the technical training of newborn resuscitation techniques such as neonatal asphyxia recovery technology;intensifying the health-care and management of migrant children and improving the ability of parents to utilize child medical service.

Objective To observe he effects of new Tangshenkang on α-SMA and E-cadherin of human renal tubular epithelial cell HK-2 in high concentrations of glucose; To explore the mechanism of new Tangshenkang on the prevention and treatment of diabetic renal fibrosis. Methods The HK-2 cells were cultured and divided into control group, high glucose group, animal serum control group, new Tangshenkang low-, medium-, and high-dosage group. After medicine intervention, cell proliferation was tested by MTT assay, and contents of α-SMA and E-cadherin were observed by ELISA assay. Results Compared with control group, α-SMA of HK-2 cultured with high glucose was much notable, but the content of E-cadherin significantly decreased, with statistical significance (P<0.05). The content of α-SMA of HK-2 cultured with new Tangshenkang decreased, and the content of E-cadherin increased; cell proliferation was markedly inhibited in culture medium supernatant of HK-2 cells cultured with high glucose plus new Tangshenkang compared with only high glucose, with statistical significance. Conclusion New Tangshenkang can inhibit cell proliferation and epithelial-myofibroblast transdifferentiation of HK-2 cell induced by high glucose, and prevent the development of diabetic renal fibrosis to a certain extent.