Global burden of acute hepatitis E between 1990 and 2019 and projections until 2030.

BACKGROUND AND AIMS: Acute hepatitis E (AHE) is still a public health issue worldwide. Here, we report the global burden of AHE in 204 countries and territories from 1990 to 2019 by age, sex and socio-demographic index (SDI), and predict the future trends to 2030. METHODS: Data on AHE were collected from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. The average annual percentage change (AAPC) and joinpoint analysis were used to determine the burden trend. RESULTS: In 2019, there were 19.47 million (95% UI, 16.04 to 23.37 million) incident cases of AHE globally, with a 19% increase since 1990. Age-standardized rate (ASR) of disability-adjusted life years (DALYs), prevalent and incident cases declined from 1990 to 2019. In 2019, the ASR of incidence, prevalence and DALYs due to HEV infection were highest in the same regions of South Asia for both sexes. Southern Sub-Saharan Africa presented the highest increases in the ASR for incidence of HEV infection in both males (AAPC = .25) and females (AAPC = .24) from 1990 to 2019. Incident cases are higher in males than females before 55-59 years old. The SDI values were negatively correlated with the age-standardized DALYs. Between 2019 and 2030, the ASR for incidence and prevalence of HEV for both sexes showed an increasing trend. CONCLUSIONS: Although the overall ASR of AHE decreased, the burden of AHE remains an underappreciated problem for society. The findings may provide useful information for policymakers to develop appropriate strategies aimed at reducing the burden of AHE.

Delayed gastric emptying after laparoscopic pancreaticoduodenectomy: a single-center experience of 827 cases.

BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.

The global, regional, and national burden of appendicitis in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide, and its burden has been changing. We report the level and trends of appendicitis prevalence, and incidence; and years lived with disability (YLD) in 204 countries and territories from 1990 to 2019, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: The numbers and age-standardized prevalence, incidence, and YLD rates per 100,000 population of appendicitis were estimated across regions and countries by age, sex, and sociodemographic index (SDI). All the estimates were reported with 95% uncertainty intervals (UIs). RESULTS: Globally, the age-standardized prevalence and incidence rates of appendicitis in 2019 were 8.7 (95% UI 6.9 to 11.0) and 229.9 (95% UI 180.9 to 291.0) per 100,000 population, with increases of 20.8% (95% UI 18.9 to 23.0%) and 20.5% (95% UI 18.7 to 22.8%) from 1990 to 2019, respectively. Additionally, the age-standardized YLDs rate was 2.7 (95% UI 1.8 to 3.9) in 2019, with an increase of 20.4% (95% UI 16.2 to 25.1%) from 1990 to 2019. In 2019, the age-standardized prevalence, incidence, and YLD rates peaked in the 15-to-19-year age groups in both male and female individuals. However, no statistically significant differences were observed between the male and female individuals in all groups. Ethiopia, India, and Nigeria showed the largest increases in the age-standardized prevalence rate between 1990 and 2019. Generally, positive associations were found between the age-standardized YLD rates and SDI at the regional and national levels. CONCLUSIONS: Appendicitis remains a major public health challenge globally. Increasing awareness of appendicitis and its risk factors and the importance of early diagnosis and treatment is warranted to reduce its the burden.

The short- and long-term outcomes of laparoscopic pancreaticoduodenectomy combining with different type of mesentericoportal vein resection and reconstruction for pancreatic head adenocarcinoma: a Chinese multicenter retrospective cohort study.

BACKGROUND: The results of laparoscopic pancreaticoduodenectomy combining with mesentericoportal vein resection and reconstruction (LPD-MPVRs) for pancreatic head adenocarcinoma are rarely reported. The aim of present study was to explore the short- and long-term outcomes of different type of LPD-MPVRs. METHODS: Patients who underwent LPD-MPVRs in 14 Chinese high-volume pancreatic centers between June 2014 and December 2020 were selected and compared. RESULTS: In total, 142 patients were included and were divided into primary closure (n = 56), end-end anastomosis (n = 43), or interposition graft (n = 43). Median overall survival (OS) and median progress-free survival (PFS) between primary closure and end-end anastomosis had no difference (both P > 0.05). As compared to primary closure and end-end anastomosis, interposition graft had the worst median OS (12 months versus 19 months versus 17 months, P = 0.001) and the worst median PFS (6 months versus 15 months versus 12 months, P < 0.000). As compared to primary closure, interposition graft had almost double risk in major morbidity (16.3 percent versus 8.9 percent) and about triple risk (10 percent versus 3.6 percent) in 90-day mortality, while End-end anastomosis had only one fourth major morbidity (2.3 percent versus 8.9 percent). Multivariate analysis revealed postoperation hospital stay, American Society of Anesthesiologists (ASA) score, number of positive lymph nodes had negative impact on OS, while R0, R1 surgical margin had protective effect on OS. Postoperative hospital stay had negative impact on PFS, while primary closure, end-end anastomosis, short-term vascular patency, and short-term vascular stenosis positively related to PFS. CONCLUSIONS: In LPD-MPVRs, interposition graft had the worst OS, the worst PFS, the highest rate of major morbidity, and the highest rate of 90-day mortality. While there were no differences in OS and PFS between primary closure and end-end anastomosis.

Incidence trends of acute viral hepatitis caused by four viral etiologies between 1990 and 2019 at the global, regional and national levels.

BACKGROUND: Hepatitis is a major public health challenge and a leading cause of death worldwide. We aimed to study the cause-specific incidence and temporal trends of acute viral hepatitis (AVH). METHODS: Data on AVH etiologies were available from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) was used to quantify temporal trend in AVH age-standardized incidence rates (ASIRs) by region, sex and aetiology. RESULTS: From 1990 to 2019, the global incidence of AVH increased by 8.02%, from 244 350 063 in 1990 to 263 951 645 in 2019, with an average decreasing ASIR of 0.52% (95% CI -0.58% to -0.45%) annually. The ASIR of AVH due to hepatitis B virus (HBV) decreased, while those of hepatitis A (HAV), hepatitis C (HCV) and hepatitis E (HEV) remained stable, with EAPCs (95% CI) of -1.47 (-1.58 to -1.36), 0 (-0.09 to 0.09), -0.35 (-0.83 to -0.13), and -0.16 (-0.41 to 0.09) respectively. Although the number of new AVH cases increased in the low sociodemographic index (SDI), low-middle SDI regions, the ASIRs decreased in all five SDI regions. Globally, HAV and HBV are the leading causes of acute hepatitis. The EAPC is significantly associated with a baseline ASIR of less than 5500 per 100 000 population (ρ = -0.44), and with the 2019 human development index (HDI) (ρ = 0.16) for AVH. CONCLUSIONS: Although the ASIR of AVH showed a generally decreasing trend, the burden of AVH remains a major public health challenge globally. The findings may be helpful for policymakers in establishing appropriate policies to reduce the viral hepatitis burden.

The global, regional, and national burden of gallbladder and biliary tract cancer and its attributable risk factors in 195 countries and territories, 1990 to 2017: A systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: The global burden of gallbladder and biliary tract cancer (GBTC) is increasing. A comprehensive evaluation of the burden is crucial to improve strategies for GBTC prevention and treatment. METHODS: The incidence rates, mortality, and disability-adjusted life years (DALYs) of GBTC from 1990 to 2017 were extracted from the Global Burden of Diseases Study (GBD) 2017. Estimated annual percent changes (EAPCs) were calculated to quantify GBTC trends during the study period. RESULTS: Globally, there were 210,878 new cases, 173,974 deaths, and 3,483,046 DALYs because of GBTC in 2017. GBTC incidence increased by 76%, mortality increased by 65%, and DALYs increased by 52% from 1990 to 2017. In addition, relatively higher Socio-Demographic Index regions had greater incidence and death rates but greatly decreased age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). At the national level, Chile had the highest ASIR (10.38 per 100,000 population) and the highest ASDR (10.43 per 100,000 population) in 2017. The largest increases in ASIR (EAPC, 3.38) and ASDR (EAPC, 3.39) were observed in Georgia. Nonlinear associations were observed between the ASDR, the Socio-Demographic Index, and DALYs at the 21 GBD regional levels and at the national level. The proportions of GBTC age-standardized deaths and DALYs attributable to high body mass index were 15.4% and 16%, respectively. CONCLUSIONS: GBTC remains a major health burden worldwide. These findings are expected to prompt policymakers to establish a cost-effective method for the early diagnosis, prevention, and treatment of GBTC, reducing its modifiable risk factors and reversing its increasing trends. LAY SUMMARY: Although the rates of age-standardized incidence, death, and disability-adjusted life-years for gallbladder and biliary tract cancer decreased from 1990 to 2017, the numbers of these measures increased. Nonlinear associations existed between the age-standardized death rate, the Socio-Demographic Index, and disability-adjusted life-years at the 21 regional and national levels in the Global Burden of Disease Study.

Laparoscopic partial splenectomy with temporary occlusion of the trunk of the splenic artery in fifty-one cases: experience at a single center.

BACKGROUND: Laparoscopic partial splenectomy (LPS) for splenic benign space-occupying lesions has been reported by many researchers; however, few studies have described methods to control intraoperative bleeding. Trustworthy experience in LPS with a satisfactory intraoperative hemorrhage control technique is therefore necessary. The current study aims to present our experience in LPS with temporary occlusion of the trunk of the splenic artery for controlling intraoperative bleeding with a large sample of 51 cases and to evaluate the safety, feasibility, and reproducibility of this technique. METHODS: Fifty-one patients from August 2014 to April 2019 who underwent LPS in our institution were retrospectively analyzed. Surgical techniques were described in detail. RESULTS: All patients had successfully undergone LPS with temporary occlusion of the trunk of the splenic artery. Conversions to open surgery, hand-assisted laparoscopic splenectomies, or blood transfusions were not needed. The operative time was 94.75 ± 18.91 min, the estimated blood loss was 71.13 ± 53.87 ml, and the volume of resected spleen was 34.75 ± 12.19%. The range of postoperative stays was 4-14 days. One female patient (2%, 1/51) suffered from postoperative complications. No perioperative mortality, incision infections, postoperative pancreatic fistulas (POPFs), splenic infarctions, or portal/splenic vein thromboembolic events occurred. CONCLUSION: LPS is an effective spleen-preserving surgery. Although there are many other bleeding control methods, temporarily occluding the trunk of the splenic artery was found to be a safe, feasible, and reproducible technique in LPS. The outcomes of this technique and the efficacy of splenic parenchyma preservation are acceptable.

The global, regional, and national burden of pancreatitis in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Pancreatitis is a critical public health problem, and the burden of pancreatitis is increasing. We report the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) for pancreatitis at the global, regional, and national levels in 195 countries and territories from 1990 to 2017, stratified by sex, age, and sociodemographic index (SDI). METHODS: Data on pancreatitis were available from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Numbers and age-standardized prevalence, incidence, and YLDs' rates per 100,000 population were estimated through a systematic analysis of modeled data from the 2017 GBD study. Both acute and chronic pancreatitis are being modeled separately in the GBD 2017; however, our data show acute and chronic pancreatitis together. Estimates were reported with uncertainty intervals (UIs). RESULTS: Globally, in 2017, the age-standardized rates were 76.2 (95% UIs 68.9 to 83.4), 20.6 (19.2 to 22.1), and 4.5 (2.3 to 7.6) per 100,000 population for the point prevalence, incidence, and YLDs, respectively. From 1990 to 2017, the percent changes in the age-standardized prevalence and YLDs rates increased, whereas the age-standardized incidence rate decreased. The global prevalence increased with age up to 60-64 years and 44-49 years in females and males, respectively, and then decreased, with no significant difference between females and males. The global prevalence rate increased with age, peaking in the 95+ age group, with no difference between sexes. Generally, positive correlation between age-standardized YLDs and SDIs at the regional and national levels was observed. Slovakia (297.7 [273.4 to 325.3]), Belgium (274.3 [242.6 to 306.5]), and Poland (266.7 [248.2 to 284.4]) had the highest age-standardized prevalence rates in 2017. Taiwan (Province of China) (104.2% [94.8 to 115.2%]), Maldives (72.4% [66.5 to 79.2%]), and Iceland (64.8% [57.2 to 72.9%]) had the largest increases in age-standardized prevalence rates from 1990 to 2017. CONCLUSIONS: Pancreatitis is a major public health issue worldwide. The age-standardized prevalence and YLDs rates increased, but the age-standardized incidence rate decreased from 1990 to 2017. Improving the quality of pancreatitis health data in all regions and countries is strongly recommended for better monitoring the burden of pancreatitis.

A robust twelve-gene signature for prognosis prediction of hepatocellular carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) patients remains poor. Identifying prognostic markers to stratify HCC patients might help to improve their outcomes. METHODS: Six gene expression profiles (GSE121248, GSE84402, GSE65372, GSE51401, GSE45267 and GSE14520) were obtained for differentially expressed genes (DEGs) analysis between HCC tissues and non-tumor tissues. To identify the prognostic genes and establish risk score model, univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed based on the integrated DEGs by robust rank aggregation method. Then Kaplan-Meier and time-dependent receiver operating characteristic (ROC) curves were generated to validate the prognostic performance of risk score in training datasets and validation datasets. Multivariable Cox regression analysis was used to identify independent prognostic factors in liver cancer. A prognostic nomogram was constructed based on The Cancer Genome Atlas (TCGA) dataset. Finally, the correlation between DNA methylation and prognosis-related genes was analyzed. RESULTS: A twelve-gene signature including SPP1, KIF20A, HMMR, TPX2, LAPTM4B, TTK, MAGEA6, ANX10, LECT2, CYP2C9, RDH16 and LCAT was identified, and risk score was calculated by corresponding coefficients. The risk score model showed a strong diagnosis performance to distinguish HCC from normal samples. The HCC patients were stratified into high-risk and low-risk group based on the cutoff value of risk score. The Kaplan-Meier survival curves revealed significantly favorable overall survival in groups with lower risk score (P < 0.0001). Time-dependent ROC analysis showed well prognostic performance of the twelve-gene signature, which was comparable or superior to AJCC stage at predicting 1-, 3-, and 5-year overall survival. In addition, the twelve-gene signature was independent with other clinical factors and performed better in predicting overall survival after combining with age and AJCC stage by nomogram. Moreover, most of the prognostic twelve genes were negatively correlated with DNA methylation in HCC tissues, which SPP1 and LCAT were identified as the DNA methylation-driven genes. CONCLUSIONS: We identified a twelve-gene signature as a robust marker with great potential for clinical application in risk stratification and overall survival prediction in HCC patients.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: The clinical utility of sorafenib plus hepatic arterial infusion chemotherapy (SoraHAIC) in advanced hepatocellular carcinoma (HCC) patients remains unclear. We, therefore, conducted the current meta-analysis to systematically evaluate the efficacy and safety of SoraHAIC therapy on major outcomes with advanced HCC patients. METHODS: A systematic search of The Cochrane Library, PubMed, and Embase databases was performed. The major outcomes in patients with advanced HCC were divided into SoraHAIC group and sorafenib group, which included overall response rate, overall survival, progressive disease, and adverse events. RESULTS: Involving a total of 726 patients from 5 included studies, our meta-analysis demonstrated that SoraHAIC showed significantly more improvement than sorafenib alone in overall response rate [risk ratio=3.08; 95% confidence interval (CI), 1.38-6.89; P=0.006] and complete response (risk ratio=5.84; 95% CI, 1.85-18.45; P=0.003). With regard to survival outcome, the combination therapy also significantly prolongs the median overall survival than sorafenib monotherapy (hazard ratio=0.59; 95% CI, 0.35-1.00; P=0.05). In addition, the risk of adverse events such as anemia, neutropenia, and thrombocytopenia was significantly greater in the combination group than in the sorafenib group (P<0.05 for all). CONCLUSIONS: This meta-analysis indicated that SoraHAIC seems to be efficient and safe for advanced HCC patients. However, additional large-scale randomized controlled trials are needed to further investigate the clinical benefit.

[Application of Early Splenic Artery Occlusion in Laparoscopic Spleen-preserving Distal Pancreatectomy using Kimura Technique].

OBJECTIVE: To present our institutional experience in laparoscopic spleen-preserving distal pancreatectomy (Lap-SPDP) using Kimura technique with or without early occlusion of the root of the splenic artery. In addition, to explore the safety and feasibility of this occlusion technique, especially its advantages in intraoperative hemorrhage control and spleen preservation. METHODS: From February 2011 to May 2019, 54 consecutive patients who were diagnosed as benign or low-grade malignant space-occupying lesions at the body and the tail of pancreas underwent Lap-SPDP using Kimura technique in our institution. Twenty-five patients before 2015 were allocated into non-occlusion group and 29 patients after 2015 were allocated into occlusion group. The non-occlusion group underwent direct dissection of the distal pancreas with blood supply from the splenic artery as well as traditional traction of the splenic artery without occlusion. Whereas the occlusion group underwent temporary occlusion of the root of the splenic artery by Bulldog clip after transecting the neck of the pancreas and distal pancreas was excised under a relatively bloodless situation. Surgical techniques were described in detail. Data between groups were retrospectively collected and stratification analysis was performed based on the diameter of tumor (>3 cm or ≤3 cm). RESULTS: Before stratification, there was a statistical difference in age between the two groups ( P=0.033), but no difference in body mass index (BMI) ( P=0.069). The median lesion diameter of the two groups was 2.5 cm and 4 cm, respectively, with no statistical difference ( P=0.065). The success rates of spleen preservation in the two groups were 93.1% and 92% respectively, showing no significant difference ( P=1.000). The length of hospital stay was slightly longer in the non-occlusion group than that in the occlusion group ( P=0.020). Comparing with the non-occlusion group, the occlusion group had significantly shorter operation time (median, 165 min vs. 235 min) and less estimated blood loss (median, 100 mL vs. 200 mL) ( P<0.05). After stratification by the tumor diameter, there were 2 cases of failed spleen preservation both in occlusion and non-occlusion group with tumor diameter >3 cm (occlusion group: 2/8, 25% and non-occlusion group: 2/14,14.3%). However there was no statistical difference between the two groups ( P=0.602). When the tumor diameter ≤3 cm, the spleen preservation rate of both groups reached 100%. When the tumor diameter was >3 cm, the operation time of the occlusion group was shorter than that of the non-occlusion group ( P=0.005). In terms of intraoperative blood loss, regardless of tumor size, the occlusion group had less estimated blood loss than that of the non-occlusion group ( P<0.05). In the occlusion group, no conversion or blood transfusion was needed intraoperatively and/or postoperatively. After stratification, there was no difference in the length of hospital stay between two groups ( P>0.05). During the follow-up period (median (Min-Max), 13.5 (3-96) months), no perioperative death, disease recurrence, portal vein or splenic vein thrombosis, gastric varices or upper gastrointestinal bleeding was noted. CONCLUSION: Lap-SPDP using Kimura technique with early occlusion of the root of splenic artery was safe and feasible and could be generally applied. By using this technique, we could reduce the operation time and blood loss, as well as sustain a high probability of spleen preservation.

[Role of PpIX-based photodynamic therapy in promoting the damage and apoptosis of colorectal cancer cell and its mechanisms].

OBJECTIVE: To explore the effects of protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) on induction of apoptosis and death in colon cancer cell and the underlying mechanisms.
 Methods: The cell killing effect of PDT on HCT116 cell was determined by cell counting kit (CCK). The cells were divided into a control group, a single light group, a single PpIX group, and a PDT group. Hoechst 33342 and flow cytometry was used to assess the cell apoptosis. Western blot was employed to analyze the expressions of bcl-2, bax, and caspase-3. Reactive oxygen species (ROS) was detected by flow cytometry.
 Results: The viability of HCT116 cell was decreased gradually with the increase of irradiation dose (P<0.05). Compared to the other 3 groups, ROS production, the number of apoptotic cells and the protein expressions of bax and caspase-3 in PDT group increased, while bcl-2 expression was decreased (P<0.05).
 Conclusion: PpIX-mediated PDT can enhance the apoptosis in HCT116 cell, which may be related to mitochondrial apoptosis pathway.

Gemcitabine plus cisplatin versus gemcitabine alone in the treatment of pancreatic cancer: a meta-analysis.

BACKGROUND: Pancreatic cancer ranks as the fourth leading cause of cancer-related mortality in the USA. And gemcitabine has been the standard of care for advanced pancreatic cancer. However, a combined use of gemcitabine plus cisplatin (GemCis) has shown promising efficacies in pancreatic cancer patients. Here, system review and meta-analysis were performed to compare the efficacy and safety of GemCis versus gemcitabine (Gem) alone in the treatment of pancreatic cancer. METHODS: The databases of MEDLINE (PubMed), EMBASE, and Cochrane Library were systematically searched for retrieving the relevant publications prior to 31 September 2014. The primary end point was overall survival (OS) and secondary end points included 6-month survival, 1 year survival, overall response rate (ORR), clinical benefit rate (CBR), time to progression/progression-free survival (TTP/PFS), and toxicities. RESULTS: A total of nine randomized controlled trials involving 1354 patients were included for systematic evaluations. Overall, as compared with Gem alone, GemCis significantly improved the 6-month survival rate (relative risk (RR) = 1.303, 95% confidence interval (CI) 1.090-1.558, P = 0.004), ORR (RR = 1.482, 95% CI 1.148-1.913, P = 0.003), PFS/TTP (hazard ratio (HR) = 0.87; 95% CI 0.78-0.93, P = 0.022), and the overall toxicities (RR = 2.164, 95% CI 1.837-2.549, P = 0.000). However, no significance difference existed in overall survival (HR = 0.90, 95% CI 0.80-1.42, P = 1.02), 1-year survival rate (RR = 0.956, 95% CI 0.770-1.187, P = 0.684), and CBR (RR = 0.854, 95% CI 0.681-1.072, P = 0.175). As for grade III/IV toxicity, seven kinds of toxicities were higher in the GemCis group. However, no significant inter-group statistical differences existed in the incidence of leukopenia, thrombocytopenia, or diarrhea. CONCLUSIONS: Despite a higher incidence of three-fourths toxicity, GemCis offers better outcomes of ORR, PFS/TTP, and 6-month survival, which indicates GemCis may be a promising therapy for pancreatic cancer.

Bioactive Coumarins from the Stems of Clausena emarginata.

Five new coumarins, clauemarmarins I - M (1 - 4), together with 10 known analogs (5 - 14), were isolated from the stems of Clausena emarginata. Compounds 8 - 13 were obtained from this plant for the first time. Their structures were established and elucidated by comprehensive analysis of spectroscopic data. The absolute configurations of 1 - 4 were further determined by their electronic circular dichroism spectroscopy. Compounds 5, 7, 12, and 14 exhibited inhibitory effects on LPS-induced NO production. Compounds 5 - 7 showed selective neuroprotective effects in Aß25 - 35 model at 10 µm.

Limonoids with neuroprotective activity from the stems of Clausena emarginata.

Two new limonoids, clauemargines M-N (1-2), together with five known compounds (3-7), were isolated from the stems of Clausena emarginata, and compounds 6 and 7 were gained from this plant for the first time. Their structures were established and elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1-2 were further determined by the octant rule of saturated cyclic ketone. Compounds 1, 2, 4, and 5 showed moderate neuroprotective effects against L-glutamic acid-induced cellular damage in human neuroblastoma SK-N-SH cells at 10 µM.

[Combination analysis of new drug discovery with "Xiaohe Silian" method and traditional Chinese medicine clinical pharmacy].

With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning.

Background and aims: Cuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI). Methods: The datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes. Results: Seventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues. Conclusion: Our findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI.

Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification.

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. PANoptosis is a recently unveiled programmed cell death pathway, Nonetheless, the precise implications of PANoptosis within the context of HCC remain incompletely elucidated. Methods: We conducted a comprehensive bioinformatics analysis to evaluate both the expression and mutation patterns of PANoptosis-related genes (PRGs). We categorized HCC into two clusters and identified differentially expressed PANoptosis-related genes (DEPRGs). Next, a PANoptosis risk model was constructed using LASSO and multivariate Cox regression analyses. The relationship between PRGs, risk genes, the risk model, and the immune microenvironment was studies. In addition, drug sensitivity between high- and low-risk groups was examined. The expression profiles of these four risk genes were elucidate by qRT-PCR or immunohistochemical (IHC). Furthermore, the effect of CTSC knock down on HCC cell behavior was verified using in vitro experiments. Results: We constructed a prognostic signature of four DEPRGs (CTSC, CDCA8, G6PD, and CXCL9). Receiver operating characteristic curve analyses underscored the superior prognostic capacity of this signature in assessing the outcomes of HCC patients. Subsequently, patients were stratified based on their risk scores, which revealed that the low-risk group had better prognosis than those in the high-risk group. High-risk group displayed a lower Stromal Score, Immune Score, ESTIMATE score, and higher cancer stem cell content, tumor mutation burden (TMB) values. Furthermore, a correlation was noted between the risk model and the sensitivity to 56 chemotherapeutic agents, as well as immunotherapy efficacy, in patient with. These findings provide valuable guidance for personalized clinical treatment strategies. The qRT-PCR analysis revealed that upregulated expression of CTSC, CDCA8, and G6PD, whereas downregulated expression of CXCL9 in HCC compared with adjacent tumor tissue and normal liver cell lines. The knockdown of CTSC significantly reduced both HCC cell proliferation and migration. Conclusion: Our study underscores the promise of PANoptosis-based molecular clustering and prognostic signatures in predicting patient survival and discerning the intricacies of the tumor microenvironment within the context of HCC. These insights hold the potential to advance our comprehension of the therapeutic contribution of PANoptosis plays in HCC and pave the way for generating more efficacious treatment strategies.

Global burden of cirrhosis and other chronic liver diseases due to nonalcoholic fatty liver disease, 1990-2019.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of cirrhosis and other chronic liver diseases (COCLDs). AIM: To conduct a comprehensive and comparable updated analysis of the global, regional, and national burden of COCLDs due to NAFLD in 204 countries and territories from 1990 and 2019 by age, sex, and sociodemographic index. METHODS: Data on COCLDs due to NAFLD were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Numbers and age-standardized prevalence, death, and disability-adjusted life years (DALYs) were estimated through a systematic analysis of modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. The estimated annual percentage change was used to determine the burden trend. RESULTS: In 2019, the global age-standardized prevalence rate of COCLDs due to NAFLD was 15022.90 per 100000 population [95% uncertainty interval (UI): 13493.19-16764.24], which increased by 24.51% (22.63% to 26.08%) from 1990, with an estimated annual percentage change of 0.78 (95% confidence interval: 0.74-0.82). In the same year, however, the age-standardized death rate and age-standardized DALYs per 100000 population were 1.66 (95%UI: 1.20-2.17) and 43.69 (95%UI: 31.28-58.38), respectively. North Africa and the Middle East had the highest prevalence rates of COCLDs due to NAFLD. The death rate increased with age up to the 95+ age group for both sexes. Males had higher numbers of prevalence, death rate, and DALYs than females across all age groups before the 65-69 age group. The sociodemographic index was negatively correlated with the age-standardized DALYs. CONCLUSION: Globally, the age-standardized prevalence rate has increased during the past three decades. However, the age-standardized death rate and age-standardized DALYs decreased. There is geographical variation in the burden of COCLDs due to NAFLD. It is strongly recommended to improve the data quality of COCLDs due to NAFLD across all countries and regions to facilitate better monitoring of the burden of COCLDs due to NAFLD.

Global, regional, and national burden of gallbladder and biliary diseases from 1990 to 2019.

BACKGROUND: Gallbladder and biliary diseases (GABDs) are a major public health issue. AIM: To analysis the cause-specific incidence, prevalence, and years lived with disability (YLDs) and its temporal trends of GABDs at the global, regional, and national level. Data on GABD were available from the Global Burden of Disease study 2019. METHODS: The estimated annual percentage change (EAPC) was used to quantify temporal trend in GABD age-standardized incidence rates (ASIRs), age-standardized prevalence rate (ASPR), and age-standardized YLD rate (ASYR) by region, sex. We analyzed the relationship between the GABD burden and country development level using the human development index (HDI). RESULTS: In 2019, the incident cases of GABD were 52003772, with an ASIR of 63432/100000 population. Globally, the number of incident cases and ASIR of GABD increased 97% and 58.9% between 1990 and 2019. Although, the ASPR and ASYR decreased from 1990 to 2019, the number of prevalent and YLDs cases increased. The highest ASIR was observed in Italy, and the highest ASPR and ASYR was observed in United Kingdom. The highest burden of GABD was found in low-SDI region, and the burden in female was significantly higher than males. A generally negative correlation (ρ = -0.24, P < 0.05) of GABD with the EAPC and human development index (HDI) (in 2021) were observed for ASIR. What's more, no correlation in ASPR (ρ = -0.06, P = 0.39) and ASYR (ρ = -0.07, P = 0.36) of GABD with the EAPC and HDI (in 2021) were observed, respectively. CONCLUSION: GABD remain a major global public health challenge; however, the burden of GABD varies geographically. Globally, the number of incident cases and ASIR of GABD increased between 1990 and 2019. The results of our study provide insight into the global disease burden of GABD and may assist policymakers in formulating effective policies to mitigate modifiable risk factors.