Association between sex and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis.

Aim: To explore the association between sex and immune checkpoint inhibitors (ICIs). Materials & methods: We assessed the difference in survival outcomes from ICIs between sexes using an interaction test. Results: 108 studies representing 70,243 patients were included. In the first-line setting, the pooled interaction HR was 0.97 (95% CI: 0.91-1.04). In the subsequent-line setting, the pooled interaction HR was 0.85 (95% CI: 0.77-0.95). When ICIs were given as perioperative therapy or as systemic therapy in patients with positive PD-L1 expression, both men and women obtained equal survival benefits. Conclusion: Both sex, line of therapy, cancer (sub)type and PD-L1 status should be taken into account in the assessment of risk versus benefit when deciding to offer ICIs to patients.

There are many differences between men and women, and whether these differences also affect the efficacy of immune checkpoint inhibitors is important because immune checkpoint inhibitors have been widely accepted as standardized treatments for patients with malignant tumors. Previous studies have reported conflicting results. This research was conducted to reassess this sex disparity with additional available reports. We found that both men and women can benefit from immune checkpoint inhibitors, while sex should be taken into account when deciding to offer immune checkpoint inhibitors to patients who have already been heavily treated.

Causal relationship between asthma and inflammatory bowel disease : A two-sample bidirectional mendelian randomization analysis.

BACKGROUND: Based on the findings of current observational studies, asthma and inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are associated; however, their causal association cannot be established due to methodological limitations. OBJECTIVES: we use two-sample bidirectional mendelian randomization (MR) to overcome the confounding factors and explore the causal link between asthma and inflammatory bowel disease. METHODS: After selecting asthma and IBD-related genome-wide association studies (GWAS) data and screening single nucleotide polymorphisms (SNPs), MR analysis was performed by four methods: inverse variance weighted (IVW), MR-Egger, maximum likelihood, and weighted median (WM), while Cochran's Q test was used to detect heterogeneity and MR-Egger intercept to detect horizontal pleiotropy. Finally, we used the leave-one-out method and funnel plot to perform sensitivity analysis. RESULTS: We screened 57, 59, and 60 SNPs in the association analysis of asthma and IBD, CD, and UC, respectively. The results of MR analysis showed that asthma only increased the risk of CD (IVW: OR = 1.1712, 95% CI = 1.0418-1.3167, P value = 0.0082; maximum likelihood: OR = 1.1739, 95% CI = 1.0428-1.3215, P value = 0.0080). Neither forward nor reverse MR analysis revealed heterogeneity or horizontal pleiotropy. Similarly, we did not find potential directional pleiotropy by funnel plot, and the leave-one-out method did not suggest a significant effect of a single SNP on the overall results. CONCLUSIONS: we found a negative correlation between asthma and Crohn's disease, but more research is needed to confirm this.

Analysis of Airway Thickening and Serum Cytokines in COPD Patients with Frequent Exacerbations: A Heart of the Matter.

Background: Differences in lung function for Chronic Obstructive Pulmonary Disease (COPD) cause bias in the findings when identifying frequent exacerbator phenotype-related causes. The aim of this study was to determine whether computed tomographic (CT) biomarkers and circulating inflammatory biomarkers were associated with the COPD frequent exacerbator phenotype after eliminating the differences in lung function between a frequent exacerbator (FE) group and a non-frequent exacerbator (NFE) group. Methods: A total of 212 patients with stable COPD were divided into a FE group (n=106) and a NFE group (n=106) according to their exacerbation history. These patients were assessed by spirometry, quantitative CT measurements and blood sample measurements during their stable phase. Univariate and multivariate logistic regression were used to assess the association between airway thickening or serum cytokines and the COPD frequent exacerbator phenotype. Receiver operating characteristic (ROC) curves were calculated for Pi10, WA%, IL-1ß and IL-4 to identify frequent exacerbators. Results: Compared with NFE group, FE group had a greater inner perimeter wall thickness of a 10 mm diameter bronchiole (Pi10), a greater airway wall area percentage (WA%) and higher concentrations of IL-1ß and IL-4 (p<0.001). After adjusting for sex, age, BMI, FEV1%pred and smoking pack-years, Pi10, WA%, IL-ß and IL-4 were independently associated with a frequent exacerbator phenotype (p<0.001). Additionally, there was an increase in the odds ratio of the frequent exacerbator phenotype with increasing Pi10, WA%, IL-4, and IL-1ß (p for trend <0.001). The ROC curve demonstrated that IL-1ß had a significantly larger calculated area under the curve (p < 0.05) than Pi10, WA% and IL-4. Conclusion: Pi10, WA%, IL-4, and IL-1ß were independently associated with the frequent exacerbator phenotype among patients with stable COPD, suggesting that chronic airway and systemic inflammation contribute to the frequent exacerbator phenotype. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (https://www.chictr.org.cn). Its registration number is ChiCTR2000038700, and date of registration is September 29, 2020.

Stoma-site approach single-port laparoscopic versus conventional multi-port laparoscopic Miles's procedure for low rectal cancer: A prospective, randomized controlled trial.

OBJECTIVE: The aim of this study was to compare perioperative outcomes of patients with low rectal cancer after stoma-site approach single-port laparoscopic Miles procedure or conventional multi-port laparoscopic Miles procedure, as well as to evaluate the safety and efficacy of stoma-site approach single-port laparoscopic surgery in low rectal cancer. METHODS: Between September 2020 and September 2021, 51 low rectal cancer patients scheduled for Miles procedure at the Department of Gastrointestinal Surgery of Affiliated Hospital of North Sichuan Medical College were randomly assigned to the single-port laparoscopic surgery group (SPLS) and the multi-port laparoscopic surgery (MPLS) group. The perioperative outcomes were compared between the two groups. RESULTS: In this study, 25 patients underwent SPLS and 26 underwent MPLS. All patients completed the study, and there were no perioperative deaths in either group. Observation indicators such as intraoperative bleeding (39 mL vs. 41 mL), number of lymph nodes (20.12 ± 3.29 vs. 21.84 ± 3.74), average hospital stay (7.15 ± 1.52 vs. 7.64 ± 1.66), and time to flatulence (2.5d vs. 2.5d) showed no significant differences between the SPLS and MPLS groups (p > 0.05). However, the operation duration (180 min vs. 118 min) and perioperative complications showed statistically significant differences between the two groups (p < 0.05). In addition, patients in the SPLS group had significantly higher satisfaction scores than those in the MPLS group (p < 0.05). CONCLUSION: For patients with low rectal cancer requiring Miles surgery, stoma-site approach single-port laparoscopic surgery has comparable safety and efficacy to multi-port laparoscopic surgery.

Surgical treatment of gastric stump carcinoma after Whipple procedure: A case report.

RATIONALE: Gastric stump carcinoma (GSC) is very exceptional and little known after Whipple procedure, and its diagnosis and treatment are extremely difficult to handle. PATIENT CONCERNS: The patient, a 68-year-old man, visited our hospital's General surgery outpatient clinic complaining of upper abdominal pain that had been bothering him for half a month. The endoscopy revealed lesions in the stomach residual, and the pathological results suggested adenocarcinoma. The patient underwent Whipple procedure for periampullary adenocarcinoma in the 4th year ago. DIAGNOSES: The final diagnosis was gastric adenocarcinoma and its pathological stage was Ⅱ A (T3N0M0). INTERVENTIONS: The patient underwent stump gastrectomy and end-to-side esophagojejunostomy (Roux-en-Y reconstruction). OUTCOMES: The operation went smoothly and the patient recovered well with only mild bloating and nausea, and the symptoms completely disappeared during the hospital stay. LESSONS: The development of GSC several years after Whipple procedure is uncommon. This is the first case from China that has received international attention. Early diagnosis is crucial. Surgery is considered to be the most effective treatment for GSC after Whipple procedure if long-term survival is possible and surgical risks are controllable.

Harnessing interventions during the immediate perioperative period to improve the long-term survival of patients following radical gastrectomy.

Although the incidence and mortality of gastric cancer (GC) have been decreasing steadily worldwide, especially in East Asia, the disease burden of this malignancy is still very heavy. Except for tremendous progress in the management of GC by multidisciplinary treatment, surgical excision of the primary tumor is still the cornerstone intervention in the curative-intent treatment of GC. During the relatively short perioperative period, patients undergoing radical gastrectomy will suffer from at least part of the following perioperative events: Surgery, anesthesia, pain, intraoperative blood loss, allogeneic blood transfusion, postoperative complications, and their related anxiety, depression and stress response, which have been shown to affect long-term outcomes. Therefore, in recent years, studies have been carried out to find and test interventions during the perioperative period to improve the long-term survival of patients following radical gastrectomy, which will be the aim of this review.

Association Between Vitamin B6 and the Risk of Colorectal Cancer: A Meta-analysis of Observational Studies.

OBJECTIVE: This meta-analysis aimed to assess the association between vitamin B6 intake, blood PLP levels, and the risk of colorectal cancer. METHODS: The databases PubMed, Cochrane Library and Embase databases were comprehensively searched for cohort studies or case-control studies. The odds ratio (OR) and 95% confidence interval (CI) were extracted from each eligible study, and the statistical software Stata was used to perform statistical merging. RESULTS: Twenty-eight studies (20 cohort studies, 8 case-control studies) were included in our meta-analysis. The combined OR for the association between colorectal cancer risk and vitamin B6 intake was 0.80 (95% CI: 0.68-0.94), while the combined OR between blood PLP levels and colorectal cancer risk was 0.54 (95% CI: 0.35-0.84). In addition, the subgroup analysis revealed that vitamin B6 could reduce the risk of colorectal cancer in women [vitamin B6 intake OR = 0.79, 95% CI (0.65-0.96); blood PLP levels OR = 0.41, 95% CI (0.30-0.57)] and also reduce the risk of colon cancer in men and women [vitamin B6 intake OR = 0.76, 95% CI (0.64-0.91); blood PLP levels OR = 0.56, 95% CI (0.42-0.73)]. CONCLUSION: In this meta-analysis, vitamin B6 intake and blood PLP levels were inversely associated with colorectal cancer risk.

A propensity score matching investigation of short-term results of single-incision laparoscopic low anterior rectal resection via ileostomy site.

Aims: The study was performed to verify the results of single-incision laparoscopic surgery (SILS) through the ileostomy site for low rectal cancer compared with conventional laparoscopic surgery (CLS). Materials and Methods: From January 2019 to November 2021, 133 patients with low rectal cancer underwent single-incision (n = 27) or conventional (n = 106) methods of low anterior rectal resection surgery with ileostomy. All patients were balanced by propensity score matching for basic information in a ratio of 1:2, resulting in 27 and 54 in SILS and CLS groups, respectively. Results: Relative to the CLS group, the SILS group exhibited fewer leucocyte changes, shorter time to first exhaust and first bowel sounds, shorter length of hospital stay and lower Visual Analogue Score on post-operative days (POD2) and POD3. Intraoperative or post-operative complications or readmissions were comparable between the two groups. The oncologic results remained consistent between the two groups other than the number of lymph nodes dissected in group no. 253. Conclusions: Single-incision laparoscopic low rectal resection surgery through the ileostomy site has advantages in terms of reduced post-operative pain, shorter post-operative exhaust time and length of hospital stay while also achieving oncologic outcomes similar to those of conventional laparoscopy. It can be an alternative procedure for patients with low rectal cancer who require ileostomy.

Metabolome and transcriptome profiling of Theobroma cacao provides insights into the molecular basis of pod color variation.

The Theobroma cacao presents a wide diversity in pod color among different cultivars. Although flavonoid biosynthesis has been studied in many plants, molecular mechanisms governing the diversity of coloration in cacao pods are largely unknown. The flavonoid metabolite profiles and flavonoid biosynthetic gene expression in the pod exocarps of light green pod 'TAS 410' (GW), green pod 'TAS 166' (GF), and mauve pod 'TAS 168' (PF) were determined. Changes in flavonoid metabolites, particularly the anthocyanins (cyanidin 3-O-galactoside, cyanidin 3-O-glucoside, and cyanidin O-syringic acid) were significantly up-accumulated in the mauve phenotype (PF) compared to the light green or green phenotypes, endowing the pod color change from light green or green to mauve. Consistently, the PF phenotype showed different expression patterns of flavonoid biosynthetic structural genes in comparison with GW/GF phenotypes. The expression level of LAR and ANR in GW/GF was significantly higher than PF, while the expression level of UFGT in GW/GF was lower than PF. These genes likely generated more anthocyanins in the exocarps samples of PF than that of GW/GF. Simultaneously, colorless flavan-3-ols (catechin, epicatechin and proanthocyanidin) content in the exocarp samples of PF was lower than GW/GF. Additionally, MYB (gene18079) and bHLH (gene5045 and gene21575) may participate in the regulation of the pod color. This study sheds light on the molecular basis of cacao pod color variation, which will contribute to breeding cacao varieties with enhanced flavonoid profiles for nutritional applications.

Transcriptional profiling reveals differentially expressed genes involved in lipid biosynthesis during cacao seed development.

Theobroma cacao is a plant of economic value due to the use of its seed lipid for chocolate, confectionery, and cosmetic industries. The seed lipid contains a stable ratio of saturated and unsaturated fatty acids, which determines its unique melting temperature. However, little is known about the molecular mechanism determining the fatty acid ratio and lipid content in cacao. To gain insight into the unique properties of lipid synthesis in cacao, biochemical and transcriptomic approaches were used to compare the lipid accumulation between high and low lipid content cacao accessions. Lipid accumulation rates and lipid content were different between the two accessions. Moreover, differentially expressed genes were detected between high and low lipid content cacao accessions. The data allowed the identification of distinct candidate genes and furthered our understanding of lipid accumulation, potentially explaining the differences in lipid content between various cacao accessions. The results might be used to develop molecular tools and engineer alternative pathways for cacao breeding with improved lipid production potentials.

Gene structure, phylogeny and expression profile of the sucrose synthase gene family in cacao (Theobroma cacao L.).

In higher plants, sucrose synthase (Sus, EC 2.4.1.13) is widely considered as a key enzyme involved in sucrose metabolism. Although, several paralogous genes encoding different isozymes of Sus have been identified and characterized in multiple plant genomes, to date detailed information about the Sus genes is lacking for cacao. This study reports the identification of six novel Sus genes from economically important cacao tree. Analyses of the gene structure and phylogeny of the Sus genes demonstrated evolutionary conservation in the Sus family across cacao and other plant species. The expression of cacao Sus genes was investigated via real-time PCR in various tissues, different developmental phases of leaf, flower bud and pod. The Sus genes exhibited distinct but partially redundant expression profiles in cacao, with TcSus1, TcSus5 and TcSus6, being the predominant genes in the bark with phloem, TcSus2 predominantly expressing in the seed during the stereotype stage. TcSus3 and TcSus4 were significantly detected more in the pod husk and seed coat along the pod development, and showed development dependent expression profiles in the cacao pod. These results provide new insights into the evolution, and basic information that will assist in elucidating the functions of cacao Sus gene family.

Molecular cloning and expression analysis of the sucrose transporter gene family from Theobroma cacao L.

In this study, we performed cloning and expression analysis of six putative sucrose transporter genes, designated TcSUT1, TcSUT2, TcSUT3, TcSUT4, TcSUT5 and TcSUT6, from the cacao genotype 'TAS-R8'. The combination of cDNA and genomic DNA sequences revealed that the cacao SUT genes contained exon numbers ranging from 1 to 14. The average molecular mass of all six deduced proteins was approximately 56 kDa (range 52 to 66 kDa). All six proteins were predicted to exhibit typical features of sucrose transporters with 12 trans-membrane spanning domains. Phylogenetic analysis revealed that TcSUT2 and TcSUT4 belonged to Group 2 SUT and Group 4 SUT, respectively, and the other TcSUT proteins were belonging to Group 1 SUT. Real-time PCR was conducted to investigate the expression pattern of each member of the SUT family in cacao. Our experiment showed that TcSUT1 was expressed dominantly in pods and that, TcSUT3 and TcSUT4 were highly expressed in both pods and in bark with phloem. Within pods, TcSUT1 and TcSUT4 were expressed more in the seed coat and seed from the pod enlargement stage to the ripening stage. TcSUT5 expression sharply increased to its highest expression level in the seed coat during the ripening stage. Expression pattern analysis indicated that TcSUT genes may be associated with photoassimilate transport into developing seeds and may, therefore, have an impact on seed production.

Molecular cloning and mRNA expression profile of sucrose transporter gene BnSUT1C from Brassica napus L.

The genomic and cDNA sequences of BnSUT1C were isolated from B. napus. Combination of cDNA and genomic DNA sequences revealed that the BnSUT1C gene contained three exons and two introns. The cDNA encodes a protein of 513 amino acids with a calculated molecular mass of 54.7 kDa and an isoelectric point of 9.12. It exhibits typical features of sucrose transporter with 12 trans-membranes spanning domains. BnSUT1C showed highly homologous with AtSUC1 and AtSUC5. A histidine residue, which is conserved across all functional sucrose transporter proteins in higher plants, is located at position 66 of the BnSUT1C. Two putative pollen-specific cis-elements, AGAAA and GTGA motifs, are located in 5'-upstream of BnSUT1C. The spatial and temporal expression patterns carried out by semi-quantitative RT-PCR and Real-Time PCR, which indicated that BnSUT1C predominantly expressed in later developmental stages of anther, as tapetal cells began to shrink and collapse. BnSUT1C could mediate the uptake of sucrose in the pollen and retrieval of tapetal degenerated products during pollen maturation.