Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

[Effects of high-fat and low-carbohydrate diet combined with radiotherapy on tumor microenvironment of Lewis lung cancer bearing mice].

Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Hyperoside attenuates carbon tetrachloride-induced hepatic fibrosis via the poly(ADP-ribose)polymerase-1-high mobility group protein 1 pathway.

Oxidative stress and inflammation have been implicated in hepatic fibrosis. Antioxidant and anti-inflammatory activities are among the pharmacological effects of hyperoside. This study aimed to evaluate the impact of hyperoside on hepatic fibrosis and elucidate the underlying processes that perpetuate this relationship. The findings indicated that hyperoside significantly protects mouse livers against damage, inflammation, and fibrosis. Specifically, attenuation of hepatic fibrosis is associated with lower expression of HMGB1 protein and reduced expression of Toll-like receptor 4, PARP-1, and nuclear factor-kB (NF-κB) p65 mRNA and protein. Furthermore, hyperoside inhibited the cytoplasmic translocation of HMGB1 and nuclear localization of NF-κB p65 in the hepatic tissues of mice. The results of this study indicate that hyperoside may impose a blocking or reversing effect on hepatic fibrosis; additionally, the corresponding hyperoside-dependent mechanism may be linked to PARP-1-HMGB1 pathway regulation.

[Anatomical classification of and laparoscopic surgery for left-sided colorectal cancer with persistent descending mesocolon].

Objective: To investigate anatomical morphology and classification of persistent descending mesocolon (PDM) in patients with left-sided colorectal cancer, as well as the safety of laparoscopic radical surgery for these patients. Methods: This is a descriptive study of case series. Relevant clinical data of 995 patients with left colon and rectal cancer who had undergone radical surgery in Fujian Medical University Union Hospital from July 2021 to September 2022 were extracted from the colorectal surgery database of our institution and retrospectively analyzed. Twenty-four (2.4%) were identified as PDM and their imaging data and intra-operative videos were reviewed. We determined the distribution and morphology of the descending colon and mesocolon, and evaluated the feasibility and complications of laparoscopic surgery. We classified PDM according to its anatomical characteristics as follows: Type 0: PDM combined with malrotation of the midgut or persistent ascending mesocolon; Type 1: unfixed mesocolon at the junction between transverse and descending colon; Type 2: PDM with descending colon shifted medially (Type 2A) or to the right side (Type 2B) of the abdominal aorta at the level of the origin of the inferior mesentery artery (IMA); and Type 3: the mesocolon of the descending-sigmoid junction unfixed and the descending colon shifted medially and caudally to the origin of IMA. Results: The diagnosis of PDM was determined based on preoperative imaging findings in 9 of the 24 patients (37.5%) with left-sided colorectal cancer, while the remaining diagnoses were made during intraoperative assessment. Among 24 patients, 22 were male and 2 were female. The mean age was (63±9) years. We classified PDM as follows: Type 0 accounted for 4.2% (1/24); Type 1 for 8.3% (2/24); Types 2A and 2B for 37.5% (9/24) and 25.0% (6/24), respectively; and Type 3 accounted for 25.0% (6/24). All patients with PDM had adhesions of the mesocolon that required adhesiolysis. Additionally, 20 (83.3%) of them had adhesions between the mesentery of the ileum and colon. Twelve patients (50.0%) required mobilization of the splenic flexure. The inferior mesenteric artery branches had a common trunk in 14 patients (58.3%). Twenty-four patients underwent D3 surgery without conversion to laparotomy; the origin of the IMA being preserved in 22 (91.7%) of them. Proximal colon ischemia occurred intraoperatively in two patients (8.3%) who had undergone high ligation at the origin of the IMA. One of these patients had a juxta-anal low rectal cancer and underwent intersphincteric abdominoperineal resection because of poor preoperative anal function. Laparoscopic subtotal colectomy was considered necessary for the other patient. The duration of surgery was (260±100) minutes and the median estimated blood loss was 50 (20-200) mL. The median number of No. 253 lymph nodes harvested was 3 (0-20), and one patient (4.2%) had No.253 nodal metastases. The median postoperative hospital stay was 8 (4-23) days, and the incidence of complications 16.7% (4/24). There were no instances of postoperative colon ischemia or necrosis observed. One patient (4.2%) with stage IIA rectal cancer developed Grade B (Clavien-Dindo III) anastomotic leak and underwent elective ileostomy. The other complications were Grade I-II. Conclusions: PDM is frequently associated with mesenteric adhesions. Our proposed classification can assist surgeons in identifying the descending colon and mesocolon during adhesion lysis in laparoscopic surgery. It is crucial to protect the colorectal blood supply at the resection margin to minimize the need for unplanned extended colectomy, the Hartmann procedure, or permanent stomas.

Wingless/int-1induced secreted protein-1: a new biomarker for renal fibrosis.

This study aimed to detect the expression of Wnt-induced secreted protein-1 (WISP-1) in renal fibrosis (RF) and to clarify the underlying mechanism. An in vivo mousee model of unilateral ureteral obstruction (UUO) and in vitro model of fibrosis on renal tubular epithelial NRK52E cells after transforming growth factor-ß1 (TGF-ß1) stimulation were used. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and immunohistochemistry were used to detect WISP-1 and fibrosis markers, including the expression of fibronectin (FN), collagen I (Col I), collagen IV (Col IV), and α-smooth muscle actin (α-SMA). In vitro experiments showed that the expression of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in rat renal tubular epithelial cells were significantly higher than that in the control group after 48 h of TGF-ß1 stimulation. In vivo experiments showed that the expressions of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in the obstructed kidney of UUO animal models were significantly increased in mRNA and protein levels compared to normal mice. This study showed that WISP-1 may be an essential cytokine that promotes renal fibrosis, being involved in the development of renal fibrosis.

Blockade of fatty acid signalling inhibits lipopolysaccharide-induced macrophage recruitment and progression of apical periodontitis.

AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.

[Thalidomide in refractory Crohn's disease: long-term efficacy and safety].

Objective: To analyze the long-term efficacy and safety of thalidomide on refractory Crohn's disease (CD). Methods: A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed. Results: In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95%CI 80.6%-96.6%), 80.7% (95%CI 70.3%-91.1%), 53.7% (95%CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio (HR) of 3.559 for Crohn's disease activity index (CDAI) ≥220(95%CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions: This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.

TPM4 aggravates the malignant progression of hepatocellular carcinoma through negatively regulating SUSD2.

OBJECTIVE: The aim of this study was to elucidate the role of TPM4 in the progression of hepatocellular carcinoma (HCC), and to explore the potential underlying mechanism by interacting with SUSD2. PATIENTS AND METHODS: TPM4 expression levels in 41 HCC tissues and paracancerous tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between TPM4 level with the pathological indexes and overall survival of HCC patients was analyzed. TPM4 overexpression and knockdown models were constructed in Bel-7402 and Hep3B cells, respectively. Subsequently, Cell Counting Kit-8 (CCK-8) and transwell assay were conducted to assess the effects of TPM4 on the proliferative and migratory abilities of HCC cells. Dual-Luciferase reporter gene assay was performed to verify the binding relationship between TPM4 and SUSD2. In addition, the xenograft model was conducted in HCC-bearing mice administrated with Hep3B cells in vivo. Finally, the effect of TPM4 on the growth of HCC was explored. RESULTS: TPM4 was significantly upregulated in HCC tissues and cell lines. Higher rates of lymphatic and distant metastasis, as well as worse prognosis, were observed in HCC patients with higher expression level of TPM4. The overexpression of TPM4 significantly enhanced the viability and migration abilities of Bel-7402 cells. However, opposite results were observed after the knockdown of TPM4 in Hep3B cells. SUSD2 was verified to be the target of TPM4 and was negatively regulated by TPM4. SUSD2 was lowly expressed in HCC tissues and cell lines. Meanwhile, SUSD2 was considered to be responsible for TPM4-regulated progression of HCC. In mice administrated with Hep3B, the cells transfected with sh-TPM4, the tumor volume and weight of HCC were markedly reduced when compared with the controls. CONCLUSIONS: TPM4 level is correlated with high rates of lymphatic and distant metastasis, as well as poor prognosis of HCC patients. By negatively targeting SUSD2, TPM4 aggravates the progression of HCC by accelerating the proliferative and migratory abilities of HCC cells.

Analysis of serum metabolite profiles in syphilis patients by untargeted metabolomics.

BACKGROUND: Global metabolomics analysis can provide substantial information on energy metabolism, physiology, possible diagnostic biomarkers and intervention strategies for pathogens. OBJECTIVE: To gain a better understanding of the mechanisms of syphilis and analysis of serum metabolite profiles in syphilis patients. METHODS: We conducted an untargeted metabolomics analysis of serum from 20 syphilis patients and 20 healthy controls. RESULTS: A total of 2890 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Distinct differential metabolites were identified by principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis. Furthermore, five metabolites were identified as significantly different by Student's t-test, including trimethylamine N-oxide, l-arginine, lysoPC(18:0), betaine and acetylcarnitine. KEGG analysis showed that these differential metabolites were in various pathways, including Chagas disease, fatty acid biosynthesis, primary bile acid biosynthesis, Salmonella infection, ABC transporters, glycerophospholipid metabolism and choline metabolism. Among them, trimethylamine N-oxide was 3.922 times in patients with syphilis than healthy controls. CONCLUSION: Trimethylamine N-oxide may be used as an indicator to distinguish between syphilis patients and healthy controls. The changes in these metabolites suggest that Treponema pallidum affects the normal metabolic activity of host cells, providing some clues for elucidating the pathogenesis of T. pallidum.

Simvastatin alleviates bone resorption in apical periodontitis possibly by inhibition of mitophagy-related osteoblast apoptosis.

AIM: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. METHODOLOGY: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. RESULTS: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. CONCLUSIONS: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.

The effect of dexmedetomidine on expressions of inflammatory factors in patients with radical resection of gastric cancer.

OBJECTIVE: To investigate the effect of dexmedetomidine on the expressions of inflammatory factors, T-lymphocyte subgroups and nuclear factor kappa-B (NF-κB) in peripheral blood monocytes in the perioperative period of radical resection of gastric cancer. PATIENTS AND METHODS: We selected 74 patients who were admitted to our hospital for radical resection of gastric cancer between January 2012 and October 2015. All patients were randomly divided into the dexmedetomidine group and the control group. Within 15 min before anesthesia induction, patients in the dexmedetomidine group received the intravenous injection of dexmedetomidine, while the same volume saline in the control group. During the operation, the initial dosage in the dexmedetomidine group was set as 1 µg/kg followed by 0.2 µg/kg•h intravenous injection to the end of operation. Three time points were selected: 15 min before anesthesia induction (T0), 1 h before the end of operation (T1) and 24 h after operation (T2). At these time points, we detected the levels of serum inflammatory factors using enzyme-linked immune sorbent assay (ELISA), immunoturbidimetry, and flow cytometer, respectively. RESULTS: The levels of IL-1ß, IL-6, TNF-α, NF-κB and CRP at T1 and T2 were significantly elevated compared with the levels at T0, and the amplitude of elevation in the control group was significantly larger than that in the dexmedetomidine group. The expression levels of T-lymphocyte subgroup in patients in both groups were decreased at T1 (compared with the levels at T0), and the decreasing extent of the ratio of CD4+ to CD8+ in the control group was significantly larger than that in the dexmedetomidine group. Meanwhile, we found that the percentages of CD3+ and CD4+ at T1 and T2 in the control group were significantly lower than those in the dexmedetomidine group. CONCLUSIONS: Dexmedetomidine can effectively reduce the release of inflammatory factors in patients that received the radical resection of gastric cancer, and the anti-inflammation effect may be exerted through downregulating the expression of NF-κB. Besides, dexmedetomidine can also alleviate the reduction in subgroups of CD3+ and CD4+, thereby ameliorating the impaired immune functions.

The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.

BACKGROUND: The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure. METHODS: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric. RESULTS: After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87). CONCLUSIONS: Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.

Duration of the anti-androgen in men undergoing 6 months of an LHRH agonist and radiation therapy for unfavorable-risk prostate cancer and the risk of death.

BACKGROUND: Whether adding a first-generation anti-androgen (AA) to a luteinizing hormone-releasing hormone agonist in the radiotherapeutic management of unfavorable-risk prostate cancer (PC) reduces the risk of all-cause and PC-specific mortality (ACM and PCSM) among men within differing comorbidity subgroups is unknown. METHODS: Between 1995 and 2001, 206 men with unfavorable-risk PC were enrolled in a randomized trial comparing radiation with or without 6 months of androgen-deprivation therapy (ADT). Partial AA use (median: 4.2 months) occurred in 29 of the 102 men randomized to ADT. Cox, and Fine and Gray's regressions were used to evaluate the impact of full versus partial AA use on PCSM and ACM-risk within comorbidity subgroups. RESULTS: After a median follow-up of 16.62 years, 156 men died. In men with moderate to severe comorbidity increasing death was observed as treatment transitioned from no to partial to full ADT (P=0.02) with an increased ACM-risk with full versus partial AA use (adjusted hazard ratio (AHR), 2.25 (95% confidence interval (CI), 0.94-5.41); P=0.07); whereas only 1 and no PC deaths occurred in men receiving a partial versus full AA course, respectively. Among men with no or minimal comorbidity there was no decrease in ACM (AHR, 0.97 (95% CI, 0.49-1.91); P=0.92) or PCSM-risk (AHR 0.39 (95% CI 0.07-52.18); P=0.28) in comparing full versus partial AA use. CONCLUSION: Increasing AA use by 2 months does not appear to impact survival in men with localized unfavorable-risk PC and no or minimal comorbidity, but may shorten survival in men with moderate to severe comorbidity, raising concern regarding in whom and for how long the AA should be prescribed.

Application of peripherally inserted central catheter in acute myeloid leukaemia patients undergoing induction chemotherapy.

Increasingly, peripherally inserted central catheters (PICC) are applied in patients with haematological malignancies. The feasibility and safety of PICC for induction chemotherapy in acute myeloid leukaemia (AML) remain unclear. Medical records of 89 newly diagnosed adult de novo AML patients, who achieved complete remission, were retrospectively reviewed (PICC group, n = 43; intravenous [IV] line group, n = 46). Patients' clinical characteristics and the number of blind punctures for blood sampling were compared between these two groups, and risk factors associated with bacteraemia were identified by univariate analysis. Patients in the PICC group experienced significantly fewer blind punctures than those in the IV line group (3.3 ± 3.6 vs. 14.4 ± 6.0; p = .000); 20.9% of PICC patients had bacteraemia, compared with 23.9% in the IV line group (p = .803). Most patients (76.7%) removed their PICC because treatment was completed. PICC increased the quality of life in AML patients undergoing chemotherapy induction by reducing the number of blind blood punctures required. Bacteraemia in PICC patients was comparable to that in IV line patients. PICC is, therefore, a feasible and safe central venous device for use in AML patients.

TLR3 preconditioning enhances the therapeutic efficacy of umbilical cord mesenchymal stem cells in TNBS-induced colitis via the TLR3-Jagged-1-Notch-1 pathway.

Toll-like receptor-3 (TLR3) priming may enhance mesenchymal stem cell (MSC) immunosuppressive activity, but this mechanism has not been investigated in the context of inflammatory bowel disease. Thus, we assessed the immunosuppressive properties of TLR3-primed MSCs using a trinitrobenzene sulfonate (TNBS)-induced mouse model of colitis. Intraperitoneally injected polyribocytidylic acid (poly (I:C)- (a ligand of TLR3) primed human umbilical cord-derived MSCs (hUC-MSCs) migrated to the inflamed colon and effectively improved clinical and pathological manifestations in colitic mice compared with mice treated with unstimulated hUC-MSCs (UCMs). Poly (I:C)-MSCs decreased a wide range of inflammatory cytokines and increased systemic interleukin-10 (IL-10) levels in colonic tissues. Poly (I:C)-MSCs also impaired T-helper type 1/17 (Th1/17) cell expansion and enhanced the suppressive effects of regulatory T cells (Treg) in vitro and in vivo. Poly (I:C)-MSCs suppressed the proliferation of activated mesenteric lymph node (MLN) cells via the overproduction of prostaglandin E2 (PGE2) and upregulation of Jagged-1. PGE2 produced by hUC-MSCs in response to poly (I:C) increased the production of IL-10 and promoted the differentiation of Treg, which could be reversed by inhibition of Notch-1. Collectively, preconditioning MSCs with poly (I:C) enhanced the therapeutic effects of hUC-MSCs in TNBS-induced colitis, and TLR3-activated Notch-1 signaling regulated the immune suppression of hUC-MSCs through the production of PGE2.

Correlation between polymorphisms in the estrogen receptor α gene and coronary heart disease: A meta-analysis.

The aim of this study was to conduct a systematic evaluation the correlation between polymorphisms in the estrogen receptor α gene (ESRα) and coronary heart disease susceptibility. Case-control studies until August 2015 analyzing the correlation between the ESRα PvuII T/C polymorphism and coronary heart disease were obtained from various electronic databases (CBM, CNKI, Wanfang Data, VIP, and MEDLINE, Cochrane Library, Embase, Springer, and Ovid. The data obtained from these studies were evaluated and valid data was extracted. A meta-analysis was performed using RevMan 5.0. Eleven cases, comprising 1742 patients with coronary heart disease and 2012 controls, that conformed to the inclusion criteria set in this study were extracted. The results of our meta-analysis indicated that the C and T alleles, the TC+CC and TT genotypes, and the CC and TT+TC genotypes did not differ significantly. The results of this meta-analysis confirmed that there was no correlation between polymorphisms in ESRα and coronary heart disease susceptibility in the Chinese population.

[Spontaneous ovulation in in vitro fertilization-embryo transfer cycles using gonadotropin-releasing hormone antagonist: a large-sample retrospective study].

OBJECTIVE: To investigate the premature spontaneous ovulation rates in in vitro fertilization-embryo transfer (IVF-ET) cycles using gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a), as well as the risk factors for premature spontaneous ovulation. METHODS: The rates of premature spontaneous ovulation in a total of 10 612 cycles using GnRH-ant or GnRH-a were compared. Matched case-controlled study and binary logistic regression model were conducted to analyze the risk factors for premature spontaneous ovulation. RESULTS: The spontaneous ovulation rate in the whole for GnRH-a cycles was 0.15% (13/8 514), compared with a 1.62% (34/2 098) in GnRH-ant cycles (P<0.01). Further matched controlled study and regression analyze found out that higher basal FSH level was a predominant risk and prediction factor for spontaneous ovulation (OR=1.20, P=0.009). CONCLUSIONS: In GnRH-ant cycles, spontaneous ovulation rate is about 10 times than which in GnRH-a cycles. Diminished ovarian function is a predominate risk factor for premature spontaneous ovulation.