Unravelling infiltrating T-cell heterogeneity in kidney renal clear cell carcinoma: Integrative single-cell and spatial transcriptomic profiling.

Kidney renal clear cell carcinoma (KIRC) pathogenesis intricately involves immune system dynamics, particularly the role of T cells within the tumour microenvironment. Through a multifaceted approach encompassing single-cell RNA sequencing, spatial transcriptome analysis and bulk transcriptome profiling, we systematically explored the contribution of infiltrating T cells to KIRC heterogeneity. Employing high-density weighted gene co-expression network analysis (hdWGCNA), module scoring and machine learning, we identified a distinct signature of infiltrating T cell-associated genes (ITSGs). Spatial transcriptomic data were analysed using robust cell type decomposition (RCTD) to uncover spatial interactions. Further analyses included enrichment assessments, immune infiltration evaluations and drug susceptibility predictions. Experimental validation involved PCR experiments, CCK-8 assays, plate cloning assays, wound-healing assays and Transwell assays. Six subpopulations of infiltrating and proliferating T cells were identified in KIRC, with notable dynamics observed in mid- to late-stage disease progression. Spatial analysis revealed significant correlations between T cells and epithelial cells across varying distances within the tumour microenvironment. The ITSG-based prognostic model demonstrated robust predictive capabilities, implicating these genes in immune modulation and metabolic pathways and offering prognostic insights into drug sensitivity for 12 KIRC treatment agents. Experimental validation underscored the functional relevance of PPIB in KIRC cell proliferation, invasion and migration. Our study comprehensively characterizes infiltrating T-cell heterogeneity in KIRC using single-cell RNA sequencing and spatial transcriptome data. The stable prognostic model based on ITSGs unveils infiltrating T cells' prognostic potential, shedding light on the immune microenvironment and offering avenues for personalized treatment and immunotherapy.

Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions.

AIMS: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no significant differences in the primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period. CONCLUSION: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.

Bioequivalence study of two formulations of terazosin hydrochloride capsule in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: This study was conducted to assess the pharmacokinetic and safety profiles between a new oral formulation of terazosin hydrochloride capsule compared with the brand-name drug. MATERIALS AND METHODS: A randomized, open-label, single-dose, 2-period crossover study under fasting or fed conditions was conducted in healthy Chinese subjects. 24 individuals were selected, respectively. Each subject was randomized at the beginning to receive a 2-mg capsule of the test or the reference terazosin during the first period and then received the alternate formulation during the second period following a 1-week washout period. Blood samples were collected at pre-dose and up to 60 hours after administration. Plasma terazosin was quantified by a validated LC-MS/MS method. RESULTS: 48 healthy subjects were enrolled, and 47 completed the study. Cmax, AUC0-t, and AUC0-∞ were similar and the 90% CIs for the geometric mean ratios of these parameters between the two groups were all bounded within the predefined bioequivalence criterion of 80 - 125% under both fasting and fed conditions. Throughout the study period, a total of 30 treatment-emergent adverse events (TEAEs) were reported under fasting condition. 35 TEAEs were observed under fed conditions. No serious adverse event was observed. CONCLUSION: The test and reference formulations of terazosin were bioequivalent and well tolerated under both fasting and fed conditions.

Clinical characteristics of inpatients with coronavirus disease 2019 (COVID-19) in Sichuan province.

BACKGROUND: The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients. METHODS: Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared. RESULTS: Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P <  0·0001), and to have more frequent lymphopenia (79·2% vs 43·7%, P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046). CONCLUSIONS: The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.

The Effects of Rhein and Honokiol on Metabolic Profiles in a Mouse Model of Acute Pancreatitis.

BACKGROUND Acute pancreatitis (AP) is generally a self-limiting inflammatory disease, but is associated with a high mortality rate when severe. The present study aimed to investigate the effects of rhein and honokiol on AP. MATERIAL AND METHODS Thirty mice were randomly divided into 5 groups (n=6 per group): blank control, AP model, AP+rhein, AP+honokiol, and AP+rhein+honokiol. The AP model was prepared by intraperitoneal injection of cerulein and lipopolysaccharide (LPS). We observed the pathological changes of the pancreas by hematoxylin and eosin (H&E) staining. A mouse amylase kit was utilized to detect the level of amylase content in serum. Gas chromatography mass spectrometer analysis was performed to detect the differences in metabolites among the blank control, AP model, and AP+rhein+honokiol groups. RESULTS The serum amylase level was significantly higher in the AP model, which suggested that the AP model was constructed successfully. The AP+rhein+honokiol group had significantly reduced interstitial edema, inflammatory cell infiltration, hemorrhage, and necrosis. In addition, the rhein and honokiol treatment influenced some of the metabolic pathways in AP, including riboflavin metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and the pentose and glucuronate interconversions pathway. CONCLUSIONS This study showed that the combination of rhein and honokiol ameliorated pathological changes in the pancreas of mice with AP.

Identification of long noncoding RNAs biomarkers for diagnosis and prognosis in patients with colon adenocarcinoma.

BACKGROUND: In the study, we aimed to find key long noncoding RNAs (lncRNAs) significantly associated with the diagnosis of colon adenocarcinoma (COAD) and lncRNA signatures to provide survival risk prognosis for patients with COAD. METHODS: The lncRNA and messenger RNA (mRNA) expression profiles and clinical information of patients with COAD were obtained from the Cancer Genome Atlas database. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between COAD and normal tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for COAD were identified by using feature selection procedure and classification model. Functional enrichment analysis revealed the possible roles of mRNAs coexpressed with lncRNAs in some cancer-related biological processes and pathways. Receiver operating characteristic curve of these lncRNA biomarkers were obtained by using 10-fold cross-validation. Univariate and multivariate Cox regression analysis for these DElncRNAs were performed to obtain the lncRNAs related to overall survival time. The expression levels of selected DElncRNAs were validated by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: A total of 169 DElncRNAs (60 downregulated and 109 upregulated) and 1236 DEmRNAs (708 downregulated and 528 upregulated) between COAD and normal tissues were identified. Eight lncRNAs of XXbac-B476C20.9, PP7080, CDKN2B-AS1, LINC00092, CA3-AS1, HAND2-AS1, CTD-2269F5.1, and LINC01082 were selected as optimal diagnostic lncRNA biomarkers for COAD. The expression of eight optimal diagnostic lncRNA biomarkers in qRT-PCR validation was consistent with our integrated analysis. Among them, XXbac-B476C20.9 was not only one of the eight optimal diagnostic lncRNA biomarkers, but also related to the prognosis of COAD. CONCLUSION: Our study demonstrated the promising potential of XXbac-B476C20.9 as an independent biomarker for diagnosis and prognosis of patients with COAD.

[Can the management and pronostic of pancreatic adenocarcinoma be improved ?] / Adénocarcinome du pancréas : peut-on améliorer la prise en charge et le pronostic ?

Pancreatic cancer is the 10th leading cause of death worldwide. It is a very lethal and aggressive tumor, with a 5-year overall survival rate under 5 % for confirmed ductal adenocarcinoma. Even though many genes have been identified as possible treatment targets, surgery remains the only curative treatment. Imaging is essential to the initial workup and is mostly based on CT-scan and MRI studies. Resectability is based on the absence of distant metastases and arterial vasculature infiltration. 3D imaging reconstruction could add precision to the surgical evaluation. Many phase II non randomized studies have shown that neo-adjuvant chemotherapy had a positive effect on pancreatic cancer. Nevertheless this approach is only reserved for cases with locally advanced tumors.

Le cancer du pancréas est la 10e cause de décès au monde. C'est une tumeur très agressive avec un taux de survie global à cinq ans en dessous de 5 % pour les adénocarcinomes canalaires confirmés. Bien que plusieurs gènes aient pu être identifiés comme d'éventuels cibles de traitements, la chirurgie reste l'unique traitement curatif pour cette maladie. Dans le bilan initial, l'imagerie tient une place prépondérante et est surtout basée sur le CT-scan et l'IRM. Les critères de résécabilité chirurgicale sont basés sur l'absence de métastases à distance et d'infiltration des vaisseaux artériels. La reconstruction 3D des images semble apporter plus de précision afin de déterminer la stratégie chirurgicale. Plusieurs études prospectives de phase II non randomisées ont déjà montré que les traitements néoadjuvants de chimiothérapie auraient un effet bénéfique sur les cancers du pancréas. Toutefois, cette approche est pour l'instant réservée uniquement aux cas localement avancés.

[Circular RNA in human disease and their potential clinic significance].

Circular RNAs (circ RNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. They share a stable structure, high expression and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play important roles in human disease, such as cancer, neurological disorders and atherosclerotic vascular disease risk. The huge potentials of circRNAs are recently being discovered from the laboratory to the clinic. CircRNAs might be developed as a potential novel and stable biomarker and potential drugs used in disease diagnosis and treatment. Here, we review the current understanding of the roles of circRNAs in human disease and their potential clinic significance in disease.

Major hepatectomy in Bismuth types I and II hilar cholangiocarcinoma.

BACKGROUND: Historically, hilar bile duct resection (HBDR) has been regarded as the choice of treatment for Bismuth types I and II hilar cholangiocarcinoma (HCCA). The present study aimed to evaluate the advantages of major liver resection (MLR) in the treatment of patients with Bismuth types I and II HCCA when compared with HBDR. MATERIALS AND METHODS: Between January 2005 and September 2012, in total, 52 patients with Bismuth types I and II HCCA who underwent HBDR alone or MLR were included for retrospective analysis. The intraoperative outcomes, postoperative complications, and oncological outcomes including recurrence and overall or disease-free survival rate were compared. RESULTS: The MLR group had significantly higher curative resection rates compared with the HBDR group (95% versus 62.5%, P = 0.021) and lower tumor recurrence (28% versus 63%, P = 0.049), albeit with longer operating time (395.5 ± 112.7 versus 270.9 ± 98.8, P < 0.001), and higher blood transfusion requirements (70% versus 16%, P < 0.001). MLR resulted in significantly higher overall postoperative morbidity (70% versus 34.4%, P = 0.012), compared with HBDR alone. When restricted to R0 resections for all the procedures, MLR significantly increased the overall postoperative survival rate compared with the HBDR group (P = 0.016); the overall survival rate at 1, 3 y was 68.4% and 60.8% for MLR group and 59.6% and 21.9% for HBDR group, respectively. Also, the disease-free survival rate was significantly higher in patients who underwent MLR, as compared with those who underwent HBDR (53.2% versus 0% at 3 y, P = 0.005). CONCLUSIONS: Our study has shown that MLR results in higher curative resections, fewer recurrences, and increased postoperative survival rate for Bismuth types I and II HCCA as compared with HBDR alone. However, there is a need for well-designed, multicenter studies to be undertaken to better inform a decision on the standard treatment for Bismuth types I and II HCCA.

Continuous versus interrupted suture techniques of pancreaticojejunostomy after pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) has traditionally been a source of significant morbidity and potential mortality after pancreaticoduodenectomy (PD). Both patient-derived and technical factors contribute to pancreatic anastomotic failure. The continuous suture duct-to-mucosa pancreaticojejunostomy (PJ) described previously is associated with a low rate of POPF. The aim of the present study was to observe whether the new technique would effectively reduce the POPF rate in comparison with conventional interrupted suture duct-to-mucosa PJ. METHODS: Data on 255 consecutive patients, who underwent the two methods of PJ after standard PD by one group of surgeons between 2006 and 2013, were collected retrospectively from a prospective database. The primary end point was the POPF rate. The risk factors of POPF were investigated by using univariate and multivariate analyses. RESULTS: A total of 120 patients received continuous suture PJ and 135 underwent interrupted suture PJ. Rate of POPF for the entire cohort was 12.5%. There were 9 fistulas (7.5%) in the continuous anastomosis group and 23 fistulas (17%) in the interrupted anastomosis group (P = 0.022). The rates of major complications (Clavien grades 3-5) were less in the continuous anastomosis group (5%) compared with the interrupted anastomosis group (13.3%) (P = 0.023). The greatest risk factor for a POPF was pancreatic duct diameter: POPF developed in only 3 patients (3.6%) with large pancreatic ducts (≥ 3 mm) and in 29 patients (16.9%) with small pancreatic ducts (<3 mm). There were four postoperative (in-hospital) deaths (both in the interrupted anastomosis group); two of which had POPF as the proximate cause of death, followed by bleeding and sepsis. CONCLUSIONS: The continuous suture duct-to-mucosa PJ effectively reduces the POPF rate after PD in comparison with interrupted anastomosis. The results confirm increased POPF rates in patients with pancreatic duct diameter <3 mm compared with pancreatic duct diameter ≥ 3 mm.

The role of organ failure and infection in necrotizing pancreatitis: a prospective study.

OBJECTIVE: To clarify the roles of organ failure and infection in the outcome of necrotizing pancreatitis. BACKGROUND: Results of previous cohort studies that focused on the roles of infection and organ failure in acute pancreatitis are controversial. METHODS: In this study, we collected the medical records of 447 patients with necrotizing pancreatitis from January 2009 to June 2012. Data associated with organ failure and infection were analyzed. RESULTS: The overall mortality rate was 13% (58/447). Intervention was performed in 223 of 447 patients. Among these 223 patients, 134 were confirmed to be with infected necrosis by a positive culture. The mortality rate was 15% (13/89) in the sterile necrosis group and 18% (24/134) in the infected necrosis group (P = 0.52). A multivariate analysis of death predictors indicated that bacteremia (odds ratio [OR] = 2.76, 95% confidence interval [CI], 1.23-5.46, P < 0.001), age (OR = 1.07, 95% CI, 1.03-1.11, P < 0.001), American Society of Anesthesiologists class (OR = 3.56, 95% CI, 1.65-7.18, P = 0.001), persistent organ failure in the first week (OR = 16.72, 95% CI, 7.04-32.56, P < 0.001), and pancreatic necrosis (OR = 1.73, 95% CI, 1.14-2.98, P = 0.008) were significant factors. CONCLUSIONS: Among patients with necrotizing pancreatitis, the effects of organ failure on mortality are more critical than those of infection. Bacteremia, age, American Society of Anesthesiologists class, persistent organ failure in the first week, and pancreatic necrosis were identified as the predictors of mortality.

[Perioperative complications and recent results of Frey procedure in the treatment of chronic pancreatitis].

OBJECTIVE: To analyze the perioperative complications and recent results of the Frey procedure in the treatment of chronic pancreatitis. METHODS: Between February 2009 and September 2012, 104 patients with chronic pancreatitis underwent the Frey procedures. This study included 91 male and 13 female patients, with a mean age of (49 ± 11) years (range, 16 to 75 years). The most common symptoms were abdominal pain in 97 patients, diarrhea in 10 patients, obstructive jaundice in 5 patients, and 5 patients had no symptoms. Nine patients had history of pancreatic surgery. RESULTS: There was no mortality. Perioperative complications occurred in 25 patients (24.0%), included pancreatic fistula in 7 patients, delayed gastric emptying in 15 patients, bleeding in 2 patients, abdominal infection in 1 patient, pulmonary infection in 2 patients, delayed healing incision in 4 patients, and pancreatic pseudocyst in 1 patient with reoperation. Seventeen patients with preoperative hyperamylasemia had a higher risk of intranperative hemorrhea and perioperative complications rates. At a mean follow-up of (29 ± 13) months, 8 patients had missed, 2 patients had died, and 3 patients was proved to be coexisted with pancreatic carcinoma. Among 87 patients with abdominal pain, 58 patients (66.7%) have complete pain relief and 23 patients (26.4%) have substantial pain relief. However, among 5 patients without abdominal pain, 2 had recurrent abdominal pain now. Seven of 17 patients with diabetes mellitus aggravated, and new onset of diabetes mellitus was observed in 10 patients. In addition, impaired glucose tolerance was developed in 13 patients. Among 10 patients with diarrhea, the symptom of 4 patients got worse. Thirty-one patients (33.7%) newly developed exocrine insufficiency, included 12 patients treated by patients oral administration of pancreatin and 19 patients only treated by diet control. Ten patients was readmitted and 5 patients underwent reoperation, included 1 patient of pancreatic pseudocyst, 3 patients of chronic pancratitis coexisted with pancreatic carcinoma, and 1 patient of chronic pancratitis with abdominal pain and obstructive jaundice. CONCLUSIONS: Frey procedure in the treatment of chronic pancreatitis is a safe technique with low mortality and morbidity rates, but indication should be strictly controlled and pancreatic tumorigenesis should be alerted.

Pharmacokinetics and Safety of Estradiol Valerate Tablet and Its Generic: A Phase 1 Bioequivalence Study in Healthy Chinese Postmenopausal Female Subjects.

Purpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.

Impact on Pulmonary Function in a Randomized Trial of Single-Fraction and Multifraction Stereotactic Body Radiation Therapy for Pulmonary Oligometastatic Disease: An Analysis of TROG 13.01 (SAFRON II).

PURPOSE: The TROG 13.01 (SAFRON II) trial was a phase 2 multicenter trial comparing single-fraction (SF) and multifraction (MF) stereotactic body radiation therapy. Patients with 1 to 3 peripheral pulmonary oligometastases were randomized 1:1 between 28 Gy in 1 fraction and 48 Gy in 4 fractions. There were no differences between arms in efficacy or toxicity. We performed an analysis to assess changes in pulmonary function tests (PFTs) between arms over time and assessed the effect of the number and total volume of targets on PFT change over time. METHODS AND MATERIALS: A linear mixed model was used to describe the PFTs by treatment arm over time. The effect of number and volume of targets on PFTs at 6 and 12 months was assessed by a simple linear model. RESULTS: Ninety patients were randomized; 87 were treated for 133 pulmonary oligometastases. Forty-four were randomized to the SF arm and 43 to the MF arm. There were no differences in absolute or relative PFT measures of forced expiratory volume in 1 second (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), or forced vital capacity (FVC) between the 2 arms. At 12 months, there was a reduction in absolute DLCO from baseline (-1.7 mL/min/mm Hg [95% CI, -2.5 to -1.0]), relative DLCO (-5.5% [95% CI, -8.4% to -2.6%]), absolute FEV1 (-0.17 L [95% CI, -0.23 to -0.11]), and absolute FVC (-0.20 L [95% CI, -0.27 to -0.13]). In patients with multiple pulmonary targets, increase in target number (per lesion) was associated with a reduction in the absolute FEV1 at 6 months of -0.10 L (95% CI, -0.18 to -0.03; P = .007), FEV1 at 12 months of -0.10 L (95% CI, -0.20 to -0.01; P = .04), FVC at 6 months of -0.11 L (95% CI, -0.20 to -0.03; P = .014), and FVC at 24 months of -0.13 L (95% CI, -0.25 to -0.01; P = .036). Reduction in FEV1 was also seen per 10-mL increase in PTV at 12 months (-0.03 L [95% CI, -0.06 to -0.00], P = .036). The number of targets and PTV were not associated with DLCO. CONCLUSIONS: Treating multiple targets resulted in increased loss of FEV1 and FVC but not DLCO. There were no significant differences in PFT decline between SF and MF stereotactic body radiation therapy.

Standard versus extended pancreaticoduodenectomy in treating adenocarcinoma of the head of the pancreas.

OBJECTIVES: To compare the postoperative complications and survival of standard pancreatoduodenectomy (SPD) and extended pancreatoduodenectomy (EPD) in patients with resectable adenocarcinoma of the head of the pancreas. METHODS: Between January 1994 and December 2011, 165 patients with biopsy-proven adenocarcinoma of the pancreatic head were treated in West China Hospital, among whom 93 underwent SPD and 72 had EPD. Complications and survival after the surgery were analyzed retrospectively. RESULTS: The median operation time of the EPD group was longer compared with the SPD group (375 minutes vs.310 minutes, P<0.01), the volume of blood transfusion was larger (700 mL vs.400 mL, P<0.05), while the median hospital stay (13.5 days vs.12 days, P=0.79) and the total complication rates were comparable (34.7% vs.32.4%, P=0.93). The total recurrence rates of the SPD and EPD groups were not significantly different (52.7% vs. 43.1%, P=0.83). No significant differences were found between the SPD and EPD groups in 1-year (81.7% vs. 86.1%), 3-year (38.7% vs. 43.1%), 5-year (16.7% vs. 19.4%), and median survivals (19.8 months vs. 23.2 months, P= 0.52). CONCLUSION: The postoperative complications and survival donot differ significantly between SPD and EPD.

Immunogenicity of COVID-19 vaccines in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. OBJECTIVES: This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients. DATA SOURCES: Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022. STUDY ELIGIBILITY CRITERIA: We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines. PARTICIPANTS: SOT recipients who received COVID-19 vaccines. ASSESSMENT OF RISK OF BIAS: We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used. METHODS: We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls. RESULTS: A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%). CONCLUSIONS: A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.

Central pancreatectomy for benign or borderline lesions of the pancreatic neck: a single centre experience and literature review.

BACKGROUND/AIMS: To investigate the effectiveness and safety of central pancreatectomy. METHODOLOGY: We retrospectively studied 44 cases that underwent central pancreatectomy (CP), 55 patients who underwent distal pancreatectomy (DP), and 62 patients who underwent pancreatoduodenectomy (PD) for their benign or borderline pancreatic lesions; as well as the different management styles for pancreatic stumps in CP. RESULTS: The duration of surgery and length of hospital stay were shorter in the CP group than that of PD group, and blood loss was also less in CP group. There were no differences between the CP and DP groups in duration of surgery, length of hospital stay, and blood loss. The incidence of common surgical complications was higher in the PD group. There were more pancreatic fistulas (grade B/C) in CP and PD groups compared to that of the DP group. New onset or worsening of diabetes occurred only in the CP and PD groups at 4.8% and 10.9%, respectively. A pancreaticogastrostomy for distal pancreatic stumps reduced the incidence of pancreatic fistula (p=0.038). Duct-to-mucosa anastomosis had less pancreatic fistula than invagination anastomosis (p=0.017). There was no difference in incidence of pancreatic fistula between pancreaticojejunostomy and oversewing of proximal pancreatic stumps (p=0.601). CONCLUSIONS: CP is an available and safe operation for benign or borderline lesions located in the pancreatic neck. A pancreaticogastrostomy for distal pancreatic stumps or duct-to-mucosa anastomosis may reduce the risk of pancreatic fistula.

Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.

BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 µL), and interferon gamma (10(-2)-10(-1) µg/100 µL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) µg/100 µL, P<0.05, 10(-2)-10(-3) µg/100 µL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

A systematic review and meta-analysis of studies comparing laparoscopic and open distal pancreatectomy.

OBJECTIVES: Currently, laparoscopic distal pancreatectomy (LDP) is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review compares outcomes of the laparoscopic technique with those of open distal pancreatectomy (ODP) and assesses the efficacy, safety and feasibility of each type of procedure. METHODS: Comparative studies published between January 1996 and April 2012 were included. Studies were selected based on specific inclusion and exclusion criteria. Evaluated endpoints were operative outcomes, postoperative recovery and postoperative complications. RESULTS: Fifteen non-randomized comparative studies that recruited a total of 1456 patients were analysed. Rates of conversion from LDP to open surgery ranged from 0% to 30%. Patients undergoing LDP had less intraoperative blood loss [weighted mean difference (WMD) -263.36.59 ml, 95% confidence interval (CI) -330.48 to -196.23 ml], fewer blood transfusions [odds ratio (OR) 0.28, 95% CI 0.11-0.76], shorter hospital stay (WMD -4.98 days, 95% CI -7.04 to -2.92 days), a higher rate of splenic preservation (OR 2.98, 95% CI 2.18-3.91), earlier oral intake (WMD -2.63 days, 95% CI -4.23 to 1.03 days) and fewer surgical site infections (OR 0.37, 95% CI 0.18-0.75). However, there were no differences between the two approaches with regard to operation time, time to first flatus and the occurrence of pancreatic fistula and other postoperative complications. CONCLUSIONS: Laparoscopic resection results in improved operative and postoperative outcomes compared with open surgery according to the results of the present meta-analyses. It may be a safe and feasible option for patients with lesions in the body and tail of the pancreas. However, randomized controlled trials should be undertaken to confirm the relevance of these early findings.

Identification of ceRNA regulatory network in acute pancreatitis and acute recurrent pancreatitis.

OBJECTIVE: The aim of this study was to find differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs and related signaling pathways, contributing to understanding the molecular mechanism of acute recurrent pancreatitis (ARP). METHODS: First, peripheral whole blood samples from five acute pancreatitis (AP) patients, five ARP patients and five healthy individuals ( N ) were collected for RNA sequencing. Second, differentially/specifically expressed lncRNAs, miRNAs and mRNAs were identified in AP vs. N , ARP vs. N and ARP. Third, the ceRNA (lncRNA-miRNA-mRNA) networks of common/specifical lncRNAs, miRNAs and mRNAs were constructed in AP vs. N , ARP vs. N and ARP. Finally, functional analysis of common mRNAs in AP vs. N and ARP vs. N was performed. RESULTS: A total of 315 common lncRNAs, 12 common miRNAs and 909 common mRNAs were identified between AP and ARP. Ninety-four specifically expressed lncRNAs, one specifically expressed miRNAs and 286 specifically expressed mRNAs were found in ARP. Some interaction pairs were identified in AP and ARP, such as LUCAT1/NEAT1-hsa-miR-16-2-3p-HK2, CHRM3-AS2-hsa-miR-122-5p/hsa-miR-145-3p-DBH/CACNA1C, CHRM3-AS2-hsa-miR-200a-3p-PDGFD, RBM26-AS1-hsa-miR-200b-3p-FHIT and LINC00891/KTN1-AS1-hsa-miR-143-3p-tyrosine kinase (TXK). ASAP1-IT2/DGCR9-hsa-miR-342-5p-ABCC5/MAP2K6 was the only one specific interaction pair identified in ARP. Four significantly enriched signaling pathways were identified in AP vs. N and ARP vs. N , including amino sugar and nucleotide sugar metabolism (involved NPL and HK2), MAPK signaling pathway (involved CACNA1C and PDGFD), metabolic pathways (involved DBH and FHIT) and leukocyte transendothelial migration (involved TXK). CONCLUSION: The identified altered lncRNAs, miRNAs, mRNAs and related signaling pathways may be involved in the AP development and recurrence.