The combination of a prolonged treatment time window and alpha-fetoprotein benefits the tumor response of hepatocellular carcinoma patients as evaluated by the imRECIST: a single-center, retrospective study.

Background: The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. Methods: This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Results: Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). Conclusions: In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.

Comparison of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic radical antegrade modular pancreatosplenectomy (l-RAMPS) provides a new surgical approach for patients with pancreatic cancers of the body and tail. However, whether it can achieve comparable outcomes to the open RAMPS (o-RAMPS) remains an issue. METHODS: To evaluate the safety and effectiveness of l-RAMPS, the studies in the databases of Medline, Embase, and the Cochrane Library published before September 13, 2021 were searched and a meta-analysis was performed using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. The perioperative and oncological outcomes were analyzed. RESULTS: Five retrospective cohorts involving 189 patients were included for final pooled analysis. There were no significant differences in the patients' operation time, intra-abdominal bleeding rate, intra-abdominal infection rate, mild morbidity (Clavien-Dindo classification = 1), moderate to severe morbidity (Clavien-Dindo classification ≥2), overall morbidity, wound infection rate, pancreatic fistula rate, delayed gastric emptying rate, reoperation rate, length of hospital stay, postoperative mortality, R0 resection rate, and 2-year overall survival between the 2 approaches. Besides, l-RAMPS was associated with less blood loss (mean difference (MD) = -232.69, 95% confidence interval (CI) = -316.93 to -148.46, P < 0.00001) and shorter days until oral feeding (MD = -0.79, 95% CI = -1.35 to -0.22, P = 0.006). However, the pooled analysis also indicated a significantly fewer lymph nodes dissected (MD = -3.01, 95% CI = -5.59 to -0.43, P = 0.02) in l-RAMPS approach. CONCLUSIONS: Although l-RAMPS provides similar outcomes associated with benefits of minimal invasiveness compared to o-RAMPS, it harvested significantly fewer lymph nodes which might have potentially negative influence on the patients' long-term survival. L-RAMPS is still in the infancy stage and further investigation is needed to verify its feasibility.

Endoscopic Endoluminal Radiofrequency Ablation and Single-Operator Peroral Cholangioscopy System (SpyGlass) in the Diagnosis and Treatment of Intraductal Papillary Neoplasm of the Bile Duct: A Case Report and Literature Review.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare biliary benign tumor with atypical clinical features and is frequently misdiagnosed. Its treatment is limited and surgical resection is thought to be the only therapeutic option in patients with IPNB. With the aim of increasing the early diagnosis rate of IPNB and providing more therapeutic options for surgeons, we innovatively put forward the concept of combined utilization of SpyGlass and endoscopic endoluminal radiofrequency ablation (ERFA) in the diagnosis and treatment of IPNB. Case Presentation: An 85-year-old woman was referred to our hospital due to right upper quadrant abdominal pain. The image examinations indicated suspicious filling defects at the upper common bile duct. Further evaluation of SpyGlass cholangioscopy showed multiple reddish villous lesions at the left hepatic duct, and SpyBite biopsy under direct visualization demonstrated papillary low-grade dysplasia. In consideration of the advanced age and preference of the patient, the novel ERFA therapy was performed. The procedure was successful without periprocedural complications; the patient recovered uneventfully and was discharged 2 days after the operation. Upon follow-up, the patient was asymptomatic and in good physical condition at 8 months postoperatively. Conclusion: Preliminarily, we demonstrate that the strategy of a combination of SpyGlass and ERAF seems to be a promising, feasible, well-tolerated, and safe management for patients with IPNB. However, more data with larger patient volumes are needed to evaluate its outcomes further.

Alamandine protects against renal ischaemia-reperfusion injury in rats via inhibiting oxidative stress.

OBJECTIVE: This study was to determine whether alamandine (Ala) could reduce ischaemia and reperfusion (I/R) injury of kidney in rats. METHODS: Renal I/R was induced by an occlusion of bilateral renal arteries for 70 min and a 24-h reperfusion in vivo, and rat kidney proximal tubular epithelial cells NRK52E were exposed to 24 h of hypoxia and followed by 3-h reoxygenation (H/R) in vitro. RESULTS: The elevated serum creatinine (Cr), blood cystatin C (CysC) and blood urea nitrogen (BUN) levels in I/R rats were inhibited by Ala treatment. Tumour necrosis factor alpha (TNF)-α, IL-1ß, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax were increased, and Bcl2 was reduced in the kidney of I/R rats, which were reversed by Ala administration. Ala reversed the increase of TNF-α, IL-1ß, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax and the decrease of Bcl2 in the H/R NRK52E cells. Ala could also inhibit the increase of oxidative stress levels in the kidney of I/R rats. NADPH oxidase 1 (Nox1) overexpression reversed the improving effects of Ala on renal function, inflammation and apoptosis of I/R rats. CONCLUSION: These results indicated that Ala could improve renal function, attenuate inflammation and apoptosis in the kidney of I/R rats via inhibiting oxidative stress.

Clinical application of "Double R" anastomosis technique in laparoscopic pancreaticoduodenectomy procedure.

ABSTRACT: Laparoscopic pancreaticoduodenectomy (LPD) is widely used as a treatment for periampullary tumors and pancreatic head tumors. However, postoperative pancreatic fistula (POPF), which significantly affects mortality and length of hospital stay of patients, remains one of the most common and serious complications following LPD. Though numerous technical modifications for pancreaticojejunostomy (PJ) have been proposed, POPF is still the "Achilles heel" of LPD.To reduce POPF rate and other postoperative complications following LPD by exploring the best approach to manage with the pancreatic remnant, a novel duct-to-mucosa anastomosis technique named Double Layer Running Suture (Double R) for the PJ was established. During 2018 and 2020, a totally 35 patients who underwent LPD with Double R were included, data on the total operative time, PJ duration, estimated blood loss, recovery of bowel function, postoperative complications, and length of hospital stay were collected and analyzed.The average duration of surgery was (380 ±â€Š69) minutes. The mean time for performing PJ was (34 ±â€Š5) minutes. The average estimated blood loss was (180 ±â€Š155) mL. The overall POPF rate was 8.6% (3/35), including 8.6% (3/35) for the biochemical leak, 0% (0/35) for Grade B, and 0% (0/35) for Grade C. No patient suffered from biliary fistula, post-pancreatectomy hemorrhage, and intra-abdominal infection, the 30-day mortality was 0%.Double R anastomosis is potentially a safe, reliable, and rapid anastomosis with a low rate of POPF and post-pancreatectomy hemorrhage. It provides surgeons more options when performing LPD. However, its safety and effectiveness should be verified further by a larger prospective multicenter study.

Minimally invasive versus open radical resection surgery for hilar cholangiocarcinoma: Comparable outcomes associated with advantages of minimal invasiveness.

BACKGROUND: Minimally invasive surgery (MIS) provides a new approach for patients with hilar cholangiocarcinoma (HCCA). However, whether it can achieve similar outcomes to traditional open surgery (OS) remains controversial. METHODS: To assess the safety and feasibility of MIS for HCCA, a systematic review and meta-analysis was performed to compare the outcomes of MIS with OS. Seventeen outcomes were assessed. RESULTS: Nine studies involving 382 patients were included. MIS was comparable in blood transfusion rate, R0 resection rate, lymph nodes received, overall morbidity, severe morbidity (Clavien-Dindo classification > = 3), bile leakage rate, wound infection rate, intra-abdominal infection rate, days until oral feeding, 1-year overall survival, 2-year overall survival and postoperative mortality with OS. Although operation time was longer (mean difference (MD) = 93.51, 95% confidence interval (CI) = 64.10 to 122.91, P < 0.00001) and hospital cost (MD = 0.68, 95% CI = 0.03 to 1.33, P = 0.04) was higher in MIS, MIS was associated with advantages of minimal invasiveness, that was less blood loss (MD = -81.85, 95% CI = -92.09 to -71.62, P < 0.00001), less postoperative pain (MD = -1.21, 95% CI = -1.63 to -0.79, P < 0.00001), and shorter hospital stay (MD = -4.22, 95% CI = -5.65 to -2.80, P < 0.00001). CONCLUSIONS: The safety and feasibility of MIS for HCCA is acceptable in selected patients. MIS is a remarkable alternative to OS for providing comparable outcomes associated with a benefit of minimal invasiveness and its application should be considered more.

Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. METHOD: A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. RESULTS: Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. CONCLUSIONS: LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.

IDUA, NDST1, SAP30L, CRYBA4, and SI as novel prognostic signatures clear cell renal cell carcinoma.

Carcinoma of the kidney is one of the most prevalent carcinoma worldwide. The majority types of carcinoma are clear cell renal cell carcinoma (CCRCC), which consist more than 80% of the cases. As a genetically diverse disease, identification of prognosis-related genes has utmost importance in the early diagnosis and prognosis of the CCRCC. In this study, we performed gene expression profiling to identify prognosis-related genes for CCRCC. In addition, we developed and validated a gene signature-based risk score to comprehensively assess the prognostic function of differentially expressed genes. Furthermore, we performed a ROC analysis to identify the optimal cut-off point for classification risk level of the patients. Univariate Cox regression models were used to assess the association between differentially expressed genes in relation to the prognosis of patients with different stages of CCRCC. Five genes were identified significantly differentially expressed in CCRCC and associated with their survival time, namely: IDUA, NDST1, SAP30L, CRYBA4, and SI. A 5-gene signature-based risk score was developed based on the Cox coefficient of the individual genes. The prognostic value of this risk score was validated in an internal testing data set. In summary, a gene-based risk score was identified and validated, which can predict CCRCC patient survival. The potential functions of this gene expression signature and individual differentially expressed gene as prognostic targets of CCRCC were revealed by this study. Furthermore, these findings may have important implications in the understanding of the potential therapeutic method for the CCRCC patients.

Chromatin-regulatory genes served as potential therapeutic targets for patients with urothelial bladder carcinoma.

Urothelial bladder carcinoma is the ninth most common cancer in the world, with an estimated 150,000 deaths per year. Two comprehensive analysis based on The Cancer Genome Atlas urothelial bladder carcinoma reported that chromatin modifier gene mutations were common in bladder cancer. We aimed to find how the mutations and transcriptional profiles of the genes involving in chromatin modification affected the prognosis of patients. The data were retrieved from the Genomic Data Commons data portal and the gene list in pathway Chromatin Modifying Enzymes were obtained from Reactome. The expression levels and mutational profiles of the genes involving in the chromatin were utilized altogether to construct a fusion patient similarity network by similarity network fusion. The genes that were differentially expressed in one clustered group or two were identified. Fifty chromatin-regulating genes had nonsilent mutations in at least 10 patients. KMT2D, KDM6A, CREBBP, ARID1A, and ARID2 had enriched inactivating mutations. Among 399 cases where both the single-nucleotide polymorphism information and the messenger RNA expression profiles were available, 326, 23, and 50 patients were clustered into Groups 1, 2, and 3, respectively. The survival analysis suggested that the patients in these three groups had a different prognosis. Thity-one genes were identified as differentially expressed in any group. The Gene Ontology term enrichment showed that the differentially expressed genes were enriched in the immune response especially in the complement activation. Altogether, chromatin-regulatory genes were key in bladder cancer and can serve, with the differentially expressed genes, as potential therapeutic targets.

[Effects and HPA Axis Related Mechanism of Kaixin-San and Danggui-Shaoyao-San on Glucose and Lipid Metabolism in Chronic Stress Rats with High-fat Diet].

OBJECTIVE: To study the effects and potential mechanism of Kaixin-San and Danggui-Shaoyao-San on glucose and lipid metabolism in chronic stress rats fed with high-fat diet. METHODS: 50 male Wistar rats were randomly divided into normal control group (distilled water), high-fat diet with chronic stress group (distilled water), melatonin group(20 mg/kg), Kaixin-San group (445 mg/kg) and Danggui-Shaoyao-San group (3360 mg/kg). All drugs were orally administered. In addition to the normal control group, each group of rats were fed with high-fat, diet. Simultaneously, stress were carried out after drugs administration 1 h daily. The duration was lasted for six weeks. The rat body weight daily was recorded, and the 24 h period urine was collected to detect the level of urine corticosterone (CORT) after three weeks. The level of plasma intraperitoneal glucose tolerance (IVGTT) was detected after six weeks. Finally, rats were executed, and serum fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), insulin (INS), adrenocorticotropic hormone releasing hormone (CRH), adrenocorticotropic hormone (ACTH), CORT and melatonin ( MLT) were determined. The weight of adrenal gland, liver glycogen and muscle glycogen levels were detected. The adrenal gland index, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity index( ISI) were calculated. RESULTS: Compared with normal group, model rats body weight, IVGTT (120 min), plasm CORT were decreased significantly. Serum TG, TC, LDL-C and urine CORT after three weeks were increased significantly. Kaixin-San and Danggui- Shaoyao-San could regulate the above indexes. CONCLUSION: Kaixin-San and Danggui-Shaoyao-San may regulate the activity of HPA axis, and improve glucose and lipid metabolism disorder in model rats by increasing melatonin secretion.

[Isolation and identification of nine iridoid glycosides from Lamiophlomis rotata by HPLC combining PDA and MS].

OBJECTIVE: To establish a rapid chromatographic method to separate the iridoid glycosides from Lamioplomis rotata, and to identify the target compounds with PDA and MS. METHODS: Methanol-water gradient elution was used to separate and analyze the target compounds. The fluid fractions were gathered according to the chromatogram and dried with the nitrogen airflow. The mass fractions of the target compounds were determined with RP-HPLC and the structures were identified with PDA and MS. RESULTS: The purity of some compounds exceeded 90% and these 9 compounds were identified as iridoid glycosides, which were Phlorigidoside C (1), Schismoside (2), Sesamoside (3), Shanzhiside methylester (4), 6-O-Acetyl shanzhiside methylester (5), Phloyoside II (6), Penstemoside (7), Loganin (8) and 8-O-Acetyl shanzhiside methylester (9). CONCLUSION: The method is simple and practicable with high efficiency. It can be used to qualitative and quantitative analysis of the 9 iridoid glycosides in Lamiphlomis rotata and its preparations.

Simultaneous determination of four shanzhiside methylester derivatives in rabbit plasma by liquid chromatography/tandem mass spectrometry.

A simple and sensitive high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for simultaneous determination of shanzhiside methylester and its three derivatives in rabbit plasma. The method showed good linearity and no endogenous material interfered with the marked compounds and internal standard (IS) capatol peaks. Samples were processed by acetonitrile precipitation. Chromatography was performed using a C18 column (150 × 3.9 mm i.d., 4 µm). The mobile phase consisted of methanol and water (60:40, v/v) during a total run time of 7 min. The main mass parent ions and daughter ions pairs (m/z) for monitoring were: shanzhiside methylester, 429.0/267.4; 8-O-acetyl shanzhiside methylester, 470.9/411.3; loganin, 413.2/251.4; phloyoside II, 479.2/281.3; and IS 385.2/203.3. Finally, the method was applied to a pharmacokinetic study of rabbits following intravenous administration of iridoid glycosides extracted from traditional herb Lamiophlomis rotata.

Laparoscopic fenestration vs open fenestration in patients with congenital hepatic cysts: a meta-analysis.

AIM: To determine whether the outcomes of laparoscopic fenestration (LF) were superior to open fenestration (OF) for congenital liver cysts. METHODS: Comparative studies published between January 1991 and May 2010 on Medline (Ovid), Emsco, PubMed, Science Direct; Cochrane Reviews; CNKI; Chinese Biomedical Database, VIP and other electronic databases were searched. Randomized controlled trials (RCTs) and retrospective case-control studies on the management of congenital hepatic cysts were collected according to the pre-determined eligibility criteria to establish a literature database. Retrieval was ended in May 2010. Meta-analysis was performed using RevMan 5.0 software (Cochrane library). RESULTS: Nine retrospective case-control studies involving 657 patients, comparing LF with OF were included for the final pooled analysis. The meta-analysis results showed less operative time [mean difference (MD): -28.76, 95% CI: -31.03 to 26.49, P < 0.00001]; shorter hospital stay (MD: -3.35, 95% CI: -4.46 to -2.24, P < 0.00001); less intraoperative blood loss (MD: -40.18, 95% CI: -52.54 to -27.82, P < 0.00001); earlier return to regular diet (MD: -29.19, 95% CI: -30.65 to -27.72, P < 0.00001) and activities after operation (MD: -21.85, 95% CI: -31.18 to -12.51, P < 0.0001) in LF group; there was no significant difference between the two groups in postoperative complications (odds ratio: 0.99, 95% CI: 0.41 to 2.38, P = 0.98) and cysts recurrence rates. CONCLUSION: The short-term outcomes of LF for patients with congenital hepatic cysts were superior to open approach, but its long-term outcomes should be verified by further RCTs and extended follow-up.