IC Group Research Articles

Efficacy of ICI-based treatment in advanced NSCLC patients with PD-L1≥50% who developed EGFR-TKI resistance.

Platinum-based chemotherapy is still the standard of care for Epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) patients after developing EGFR-TKI resistance. However, no study focusing on the role of immuno checkpoint inhibitor (ICI) based treatments for EGFR mutated NSCLC patients who carried programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50% progressed after EGFR-TKI therapy. In this study, we retrospectively investigated the outcomes of ICI-based treatments for EGFR mutated NSCLC patients carried PD-L1 TPS≥50% after developing EGFR-TKI resistance and to explore the population that may benefited from ICI-based treatment. We retrospectively collected data of advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation at Shanghai Chest Hospital between January 2018 and June 2021. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of this study. A total of 146 patients were included. Up to June 20th, 2022, median follow-up was 36.7 months (IQR, 12.5-44.2 months). Among the population, 66 patients (45.2%) received chemotherapy, the remaning (54.8%) received ICI-based treatment, including 56 patients(70.0%) received ICI combined with chemotherapy (IC) and 24 patients (30.0%) received ICI monotherapy (IM). In IC group,31 patients received ICI combined with chemotherapy,19 patients received ICI combined with antiangiogenic therapy and remaing received ICI combined with chemotherapy and antiangiogenic therapy. Survival analysis shown that patients who received ICI-based treatment had better progress-free survival (PFS) and overall survival (OS) compared with those treated with other therapy (median PFS, 10.0 vs. 4.0 months, P<0.001; median OS, 39.5 vs. 24.2 months, P<0.001). What's more, patients who treated with IC treatment had a superior survival time than those received IM treatment (median PFS, 10.3 vs. 7.0 months, P<0.001; median OS, 41.6 vs. 32.4 months, P<0.001). Subgroup analysis found that the PFS and OS benefit of IC was evident in all subgroups. For advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation, ICI-based treatment could provide a more favorable survival than classical chemotherapy. What' s more, compared with ICI monotherapy, ICI combined with chemotherapy seems to be the preferred treatment.

Bevacizumab/PD-1 inhibitor plus chemotherapy as first-line treatment of advanced non-squamous non-small-cell lung cancer.

Aim: To compare the effectiveness of PD-1 inhibitor or bevacizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer (nsNSCLC). Methods: We retrospectively collected data for patients with advanced nsNSCLC who underwent first-line treatment with PD-1 inhibitor or bevacizumab plus chemotherapy (IC and BC groups). Propensity score matching (PSM) was adopted to balance covariates. Results: 278 patients were enrolled, after PSM (n=104/group), the objective response rate was 45.1% and 24.0% in the IC and BC groups (p=0.001). Median progression-free survival (PFS) was 13.5 and 8.2months (p=0.007), and duration of response was 14.8 versus 8.1months (p=0.007), respectively. In subgroup analysis, the PFS for those patients with PD-L1≥1% (16.2 vs 6.8months, p=0.000) was significantly longer in the IC group than that in BC group, but not in the PD-L1<1% subgroup (8.9 vs12.7months, p=0.719). Conclusion: PD-1 inhibitor plus chemotherapy was superior to bevacizumab plus chemotherapy as first-line treatment for advanced nsNSCLC, which is debatable for patients with PD-L1<1%.

Mesenchymal Stem Cells (MSCs) Treatment Alleviates Smoke Inhalation and Burn-Induced Acute Respiratory Distress Syndrome (ARDS) by Inhibiting HMGB1-TLR4 Signal

Abstract ARDS is one of the leading causes of high morbidity and mortality in trauma patients. Previously our data demonstrated autologous MSCs treatment improved survival in a swine model of smoke inhalation and burn injury. However, the pathophysiological mechanisms are still largely unknown. Twenty anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, were then randomly assigned to either mock treatment (IC, n=10), or autologous MSCs treatment (MSCs, n=10), followed by ICU care up to 72 hours except in case of early death. Three doses of MSCs collected by bone marrow aspiration and concentrated using a bedside cell concentrator device were applied at 2, 24, and 48 hours of post-injury (PI). Blood and tissue samples were collected for ELISA and IHC analyses. In IC group, 10/10 injured pigs developed ARDS, but only 6/10 pigs in MSCs group developed ARDS. Serum analysis revealed that the HMGB1 level gradually increased after injury and reached a peak at 48h PI (5.7-fold increase vs. baseline). The SDC-1 and C3a levels also increased after injury but reached a peak at 24h (2.9-fold) and 72h PI (2.2-fold), respectively. The MSCs treatment significantly reduced the HMGB1 level in the serum, especially at 6h and 12h PI compared to the IC group but failed to inhibit the SDC-1 and C3a increases. IHC analyses showed that injury triggered a significantly higher expressions of HMGB1 and TLR4, as well as co-localization of HMGB1 and TLR4 in the lung; while MSCs treatment was able to disrupt the HMGB1-TLR4 interaction and significantly reduce their expressions. Our data indicate that the way MSCs treatment mitigates ARDS might be by reducing HMGB1 release and inhibiting the HMGB1-TLR4 signal pathway activation in pigs after smoke and burn injury. This work was supported by the US Army Medical Research and Development Command (USAMRDC) under Grant No. W81XWH-13-2-0005.

The state of the cytokine profile in pregnant women with non-alcoholic fatty liver disease at the stage of non-alcoholic steatohepatitis with varying degrees of comorbid obesity under the influence of the developed complex therapy program

The aim of the study: to evaluate the cytokine profile state in pregnant women with non-alcoholic fatty liver disease (NAFLD) at the stage of non-alcoholic steatohepatitis (NASH) with varying degrees of obesity under the influence of the developed complex therapy program. Material and methods. We examined 197 pregnant women with NAFLD at the stage of NASH in combination with obesity. The main group I consisted of 98 pregnant women with NAFLD at the stage of NASH with varying degrees of obesity, who were divided into 3 subgroups depending on body mass index (BMI). Among them, 26 pregnant women with BMI of 25.0–29.9 kg/m2 were included in IA group, 48 pregnant women with BMI of 30.0–34.9 kg/m2 were included in IB group, and 24 pregnant women with BMI of 35.0–39.9 kg/m2 – in IC group. All pregnant women in the main group were prescribed complex therapy including vitamin E at a dose of 400 IU/day, ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg/day, and L-carnitine at a dose of 3 g per day. The comparison group consisted of 69 women with NAFLD at the stage of NASH and abdominal obesity, who corresponded to subgroups of the main group (IIA – 23 patients, IIB – 25 women, IIC – 21 pregnant women) and received basic therapy. The control group consisted of 30 healthy women. To evaluate the cytokine profile, levels of IL-1β, IL-6, IL-10 and TNF-α were determined by ELISPOT. Results. Analysis of the cytokine profile in women with NASH and obesity showed the presence of systemic inflammation links in the examined groups, which was manifested by increased levels of pro-inflammatory and decreased levels of anti-inflammatory interleukins in blood serum of pregnant women. A prescription of the complex treatment contributed to a decreased activity of the inflammatory response, which was manifested by an improvement in the levels of cytokine profile indicators. Conclusions. NASH during pregnancy is accompanied by significant changes in the cytokine profile. The prescription of complex therapy in the form of vitamin E, UDCA and L-carnitine is effective in the treatment of pregnant women with NAFLD at the stage of NASH due to cumulative and potentiating effects, reducing manifestations of systemic inflammation by normalizing the level of cytokines.

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT.

Since allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients' survival. We retrospectively compared patients who received venetoclax plus hypomethylating agents (VEN+HMA, n=23) or intensive chemotherapy (IC, n=42) for hematological relapse of myeloid malignancies after allo-HSCT. HMA selection included decitabine (n=2) and azacitidine (n=21), and combined donor lymphocyte infusion was administered to 21 and 42 patients in VEN+HMA and IC groups, respectively. Median age of all patients was 39 (16-64) years old. Overall response rates, including complete response (CR), CR with incomplete recovery of normal neutrophil or platelet counts (CRi) and partial response (PR), were not significantly different between VEN+HMA and IC groups (60.1% versus 64.3%, P=0.785). CR/CRi rate was 52.2% in VEN+HMA and 59.5% in IC group (P=0.567). The rate of relapse after response was 66.7% in VEN+HMA group and 40.7% in IC group (P=0.176). Median overall survival was 209.0 (95%CI 130.9-287.1) days for VEN+HMA group versus 211.0 (95%CI 28.7-393.3) days for IC group (P=0.491). The incidence of lung infection (17.4% versus 50.0%, P=0.010), thrombocytopenia (73.9% versus 95.2%, P=0.035) and acute graft-versus-host disease (aGvHD) (50.0% versus 13.0%, P=0.003) was significantly higher in IC group. In conclusion, VEN+HMA is not inferior to IC regimen in terms of improving response and survival, and is associated with a lower incidence of adverse events and aGvHD. However, further research is required to enhance long-term survival.

Unique Characteristics of Patients with Von Hippel-Lindau Disease Defined by Various Diagnostic Criteria.

Von Hippel-Lindau (VHL) disease diagnosis is based on two criteria sets: International criteria (IC, two hemangioblastomas, one hemangioblastoma plus one visceral lesion, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion); or Danish criteria (DC, two clinical manifestations, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion). We aimed to compare the characteristics of patients with VHL-related pancreatic neuroendocrine tumor (vPNET) meeting either the clinical Danish criteria only (DOC) or IC to those with sporadic PNET (sPNET). The cohort included 33 patients with VHL (20 vPNETs) and 65 with sPNET. In terms of genetic testing and family history of VHL, 90.0% of the patients with vPNET in the IC group had a germline VHL pathogenic variant, and 70.0% had a family history of VHL vs. 20% and 10% in the DOC group, respectively (p < 0.05 for both). Patients with vPNET were younger at diagnosis compared with sPNET (51.6 ± 4.1 vs. 62.8 ± 1.5 years, p < 0.05). Patients in the IC group were younger at diagnosis with VHL, vPNET, pheochromocytoma, or paraganglioma (PPGL) and renal-cell carcinoma (RCC) than those in the DOC group (p < 0.05 for all comparisons). The most prevalent presenting manifestations were hemangioblastoma (42.8%) and PPGL (33.3%) vs. RCC (58.3%) and PNET (41.7%) in the IC vs. DOC groups. In conclusion, patients with vPNET meeting DOC criteria show greater similarity to sPNET. We suggest performing genetic testing, rather than solely using clinical criteria, for establishing the diagnosis of VHL.

Assessment of Endocrine, Metabolic, and Fibrinolytic Profile and Its Association with BMI in Polycystic Ovarian Syndrome

Polycystic ovarian syndrome is a typical endocrine disorder that occurs in women and has a significant impact on the reproductive, metabolic, endocrine, and fibrinolytic systems. It is a heterogeneous clinical condition caused by multiple factors, especially obesity. Furthermore, metformin is the classical treatment approach for PCOS, which has conflicted results. The current study aimed to find out the effect of the usage of metformin on metabolic, fibrinolytic, and reproductive profiles between obese women with PCOS and non-obese women with PCOS. A cross-sectional study was carried out on 200 women diagnosed with PCOS and divided into two groups based on BMI. Each group was further subdivided into three subgroups (A, B, and C) based on their prescribed treatment. In addition, 50 age-matched controls were selected to compare the outcome. The reproductive hormones, lipid profile, glycaemic index, and fibrinolytic profile were measured in each group and compared to find the desired association. The demographic variables did not show significant variation within or between the groups except BMI. Group IA has shown better metabolic variables, Group IB has an improved endocrine profile, and Group IC has a better fibrinolytic profile(p&gt;0.01**). Group II B has shown a better metabolic and endocrine profile, whereas it is significantly higher in the fibrinolytic profile (p&gt;0.01**). Cumulatively Group II has a drastic reduction in all variables than group I(p&gt;0.01**) except few non-significant variables. Obese PCOS patients are at an increased risk for complications such as endometrial hyperplasia, metabolic syndrome, and vascular thrombosis. Metformin and OCP are highly beneficial as they reduce the risk of insulin resistance and glucose intolerance and improve ovarian functions for a better reproductive life.

Mutational profile, outcomes, and impact of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and inconclusive cytogenetic analysis.

Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p=.02). The 2-year RFS (55.9% vs. 58.5%; p=.29) and OS (61.9% vs. 66.9%; p=.48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p=.99). Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.

Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy

Objective: To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths. Methods: The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results: (1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer (P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage (HR=1.882, 95%CI: 1.305-2.716), LNM (HR=2.178, 95%CI: 1.483-3.200) and UCI (HR=3.650, 95%CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage (HR=2.500, 95%CI: 1.580-3.956), LNM (HR=2.053, 95%CI: 1.309-3.218), UCI (HR=3.984, 95%CI: 1.917-8.280), PVM (HR=3.235, 95%CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% (P=0.794), and the 5-year OS were 90.8% and 89.3% (P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions: Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Origin of the superchondritic carbon/nitrogen ratio of the bulk silicate Earth – an outlook from iron meteorites

Disagreement regarding the origin of the bulk silicate Earth’s (BSE) superchondritic carbon/nitrogen (C/N) ratio is due, in part, to the unknown C/N ratios of differentiated planetesimals – the building blocks of Earth-like rocky planets. In this study we report solid–liquid metal partitioning experiments for C and N that allow us to reconstruct, from the C and N contents of iron meteorites, the C/N ratios of the cores of the earliest formed planetesimals. Due to their siderophile character, most of the C and N retained in these bodies after differentiation resides in their cores. Therefore, estimates of the bulk C and N contents and C/N ratios of the cores yield confident estimates of these quantities in the complete parent bodies of iron meteorites. Our experimental data, at 1 GPa and 1200–1400 °C, show that C and N are incompatible in solid metal relative to S-poor liquids but compatible in solid metal relative to S-rich liquids. Crucially, N is approximately an order of magnitude more compatible than C in S-rich systems. S itself is incompatible in solid metal and so the late-crystallizing liquids persisting at the end of core freezing were S-rich for most cores. Although these late-crystallizing liquids are unsampled by iron meteorites, we infer that their N contents and C/N ratios were generally lower and higher, respectively, than those in iron meteorites. Depending upon the fraction of unsampled late-crystallizing liquids as well as their S contents, the C/N ratios of the bulk cores and complete parent bodies are either similar to or higher than those measured in iron meteorites. The reconstructed C/N ratios of most of the parent bodies of iron meteorites are chondritic, except that the volatile-rich IC and IIC groups have superchondritic C/N ratios. Importantly, the C/N ratio of the parent body of the IC iron meteorite group lies within the estimated range of the BSE, whereas the C/N ratios of all other groups are lower. Correlated depletion of moderately volatile elements like Ge and Ga with C and N, variations in metallographic cooling rates, and Pd-Ag isotope systematics suggest that the parent cores of the volatile-depleted iron meteorite groups were likely affected by volatile degassing. If volatile-rich iron meteorite groups like the IC better capture the C and N inventories of the parent cores of the earliest formed planetesimals, then delivery of C and N via such planetesimals makes the superchondritic C/N ratio of the BSE a natural consequence of the Earth’s accretion history. Otherwise, poorly constrained processes like atmospheric erosion or C and N delivery by exotic materials are required to explain the superchondritic C/N ratio of the BSE.

Effects of dietary epidermal growth factor supplementation on liver antioxidant capacity of piglets with intrauterine growth retardation.

The present experiment was conducted to study the effects of dietary epidermal growth factor (EGF) supplementation on the liver antioxidant capacity of piglets with intrauterine growth retardation (IUGR). The present study consists of two experiments. In experiment 1, six normal-birth-weight (NBW) and six IUGR newborn piglets were slaughtered within 2 to 4 h after birth to compare the effects of IUGR on the liver antioxidant capacity of newborn piglets. The results showed that compared with NBW piglets, IUGR piglets had a lower birth weight and liver relative weight; IUGR piglets had a higher serum malondialdehyde (MDA) level, liver MDA level and hydrogen peroxide (H2O2) level, and had a lower liver total antioxidant capacity (T-AOC) level and glutathione peroxidase (GSH-Px) activity; IUGR trended to increase serum alanine aminotransferase activity, aspartate aminotransferase activity, and H2O2 level, and trended to decrease liver total superoxide dismutase activity. In experiment 2, six NBW piglets, and 12 IUGR piglets weaned at 21 d of age were randomly divided into the NC group (NBW piglets fed with basal diet); IC group (IUGR piglets fed with basal diet), and IE group (IUGR piglets fed with basal diet plus 2 mg/kg EGF), and feeding for 14 d. Organ index, serum parameters, liver antioxidant capacity, and liver antioxidant-related genes expression were measured. The results showed that compared to the IC group, dietary EGF supplementation (IE group) significantly reduced serum malondialdehyde level and H2O2 level, and liver protein carbonyl (PC) level and 8-hydroxydeoxyguanosine level of piglets with IUGR; dietary EGF supplementation (IE group) significantly increased serum T-AOC level, liver T-AOC level and GSH-Px activity; dietary supplemented with EGF (IE group) enhanced liver Nrf2, NQO1, HO1, and GPX1 mRNA expression compared to IC group. Pearson's correlation analysis further showed that EGF can alleviate liver oxidative injury caused by IUGR and improve the performance of IUGR piglets. In conclusion, EGF exhibited potent protective effects on IUGR-induced liver oxidative injury, by activating the Nrf2 signaling pathway to mediate the expression of downstream antioxidant enzymes and phase II detoxification enzymes (NQO1 and HO1), thereby alleviating liver oxidative damage and promoting the growth performance of IUGR piglets.

Psychosocial characteristics pattern correlated with HIV-related risky sexual behavior among HIV-negative men who have sex with men: a latent profile analysis

Men who have sex with men (MSM) have become a high risk population of HIV infection due to their risky sexual behaviors. The latent pattern of psychosocial characteristics plays an important effect in HIV-related risky behaviors among HIV-negative MSM. Participants were recruited from Wuhan, Nanchang, and Changsha city from September 2017 to January 2018. Social support was assessed by the multidimensional scale of social support, Connor-Davidson Resilience scale-10 items for reliance, the assessment of Stigma towards Homosexuality for sexual minority stigma, the Likert subscale of nondisclosure for identity concealment, the ACE questionnaire-Kaiser-CDC for adverse childhood experience, the Centers for Epidemiological Studies Depression Scale for depression. Latent profile analysis (LPA) and multivariate regression were used to analyze the data. Three psychosocial characteristic patterns were revealed by the LPA. "Social support and resilience group" (SR group), "Identity concealment group" (IC group) and "Adverse childhood experience" (ACE group) were identified, respectively. In comparison with "SR group", "IC group" have a higher likelihood of one-night male partners (AOR = 2.74, 95%CI = [1.54, 4.90]), both fixed and one-night male partners (AOR = 2.01, 95%CI = [1.34, 3.01]) and HIV-unsure male partner (AOR = 2.12, 95%CI = [1.44, 3.13]). Similarly, "ACE group" were more likely having inconsistent condom use (AOR = 2.58, 95%CI = [1.41, 4.73]), and having sex with HIV-positive male partner (AOR = 4.90, 95%CI = [1.95, 12.30]) with comparison of "SR group". In addition, we further revealed that "ACE group" had a higher ratio (90.0%) of inconsistent condom use among MSM whose male partners were HIV-positive. Six important psychosocial factors were divided into three latent pattern classes. Compared with "SR group", "IC group" and "ACE group" were more likely to engage in HIV-related risky sexual behaviors. Further research may pay more attention to "IC group" and "ACE group" for targeted intervention.

Renal function change after radical cystectomy for urothelial carcinoma patients with a solitary kidney may be independent of urinary diversion type.

To compare renal function change by urinary diversion (UD) type (ileal conduit [IC] vs. neobladder [NB]) in patients with a single kidney who underwent radical cystectomy (RC) due to bladder cancer. We evaluated the renal function change in 86 patients with a single kidney who underwent RC between January 1999 and August 2022. Renal function was assessed using serum creatinine, serum estimated glomerular filtration rate (eGFR), eGFR difference value (preoperative and follow-up values), and eGFR difference proportion (eGFR difference value/preoperative eGFR) at 1, 3, 6, 12, 24, 36, 48, and 60 months. In addition, multiple definitions of eGFR decline were evaluated: 10 points, 10%, and 20% decline in eGFR. Cox regression models were used to identify risk factors of eGFR decline-free, recurrence-free, overall, and cancer-specific survival rates. A total of 54 patients (62.8%) underwent IC, whereas 32 (37.2%) underwent NB. Baseline characteristics were similar between the two groups except for age and body mass index. Renal functions over time by various methods did not differ significantly between the IC and NB groups. Furthermore, eGFR decline-free survival rate using different definitions was similar between the IC and NB groups. Overall survival, recurrence-free survival, and cancer-specific-free survival rates were not different between the IC and NB groups. UD type (IC vs. NB) did not impact the renal function change of patients with a single kidney who underwent RC. Therefore, patients with a single kidney might be considered to be an indication of NB.

Long-term impact of patients' compliance to peri-implant maintenance therapy on the incidence of peri-implant diseases: An 11-year prospective follow-up clinical study.

To prospectively evaluate the incidence of peri-implant diseases and the associated risk factors during 11 years of peri-implant maintenance therapy (PIMT). A sample of 80 partially edentulous individuals rehabilitated with dental implants was invited to participate in a PIMT program (T1-prior to entering the PIMT program). After 11 years, 51 individuals remained regularly or irregularly adherent to PIMT (T2-last recall after 11 years) and were classified as regular (RC; n= 27) or irregular (IC; n= 24) compliers. Data of interest were analyzed using univariate and multivariate logistic regression analyses. The incidence of peri-implant mucositis and peri-implantitis observed at T2 in the IC group (70.8% and 37.5%, respectively) were significantly higher than those observed in the RC group (37.0% and 11.1%, respectively). The incidence of peri-implant diseases was mostly attributable to potentially modifiable risk factors, as such: RC group-PM (p= 0.013); IC group-high plaque index (p< 0.001), irregular compliance (p< 0.001), the presence of PM (p= 0.015) and periodontitis (p< 0.039). Regular compliance during PIMT had a strong effect in minimizing the incidence of peri-implant diseases. Increasing regular dental visits and improving oral hygiene would provide benefits for preventing peri-implant diseases.

Alpha Lipoic Acid and Monoisoamyl-DMSA Combined Treatment Ameliorates Copper-Induced Neurobehavioral Deficits, Oxidative Stress, and Inflammation.

Copper (Cu), being an essential trace metal, plays several roles in biological processes, though exposure to Cu can be potentially toxic to the brain and a few other soft organs. In the present study, we investigated the effects of the combined administration of monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), which is a new chelator, and alpha lipoic acid (ALA) and an antioxidant that is made naturally in the body and is also found in foods, against Cu-induced oxidative stress in rats. Rats were exposed to 20 mg/kg copper sulfate for 16 weeks once a day via the oral route. After 16 weeks of exposure, animals were divided into different sub-groups. Group I was divided into three subgroups: Group IA, control; Group IB, MiADMSA (75 mg/kg, oral); Group IC, ALA (75 mg/kg, oral), while Group II was divided into four subgroups: Group IIA, Cu pre-exposed; Group IIB, Cu+ MiADMSA; Group IIC, Cu+ ALA; Group IID, Cu+ ALA+ MiADMSA. Exposure to Cu led to significant neurobehavioral abnormalities; treatment with MiADMSA, and in particular MiADMSA + ALA, significantly ameliorated the neurobehavioral parameters and restored the memory deficits in rats. Oxidative stress variables (ROS, nitrite, TBARS, SOD, catalase) and inflammatory markers (TNF-α, and IL-1β), which were altered on Cu exposed rats, also responded favorably to ALA+ MiADMSA combined treatment. Thus, combined administration of MiADMSA and ALA might be a better treatment strategy than monotherapy with MiADMSA or ALA against Cu-induced neurotoxicity, particularly in reducing oxidative stress, neurobehavioral abnormalities, and inflammatory markers.

Genetics, age, and crystallization history of group IC iron meteorites

The IC iron meteorite group is characterized utilizing nucleosynthetic mass-independent isotopic compositions and 182W age constraints, coupled with siderophile element concentration measurements and modeling of crystal-liquid fractionation processes. The six IC irons analyzed, Arispe, Bendego, Chihuahua City, Nocoleche, NWA 2743, and Winburg have indistinguishable Mo and W genetic isotopic compositions and are consistent with derivation from the same parent body, which formed in the non-carbonaceous (NC) nebular reservoir. A pre-exposure µ182W value (parts-per-million deviations in isotopic ratios from terrestrial standards) for the six IC irons of −337 ± 5 corresponds to a metal-silicate segregation age of 1.0 ± 0.4 Myr after calcium-aluminum-rich inclusion (CAI) formation. This age is similar to those determined for other NC iron groups. Siderophile element abundances of the IC irons are generally similar and characterized by minor depletions in the more volatile siderophile elements. Highly siderophile element (HSE) distributions among the IC group suggest that the initial parent body core was S-rich, with preferred model results indicating an initial melt composition with ∼ 18 wt% S, 2 wt% P and 0.03 wt% C. Processes in addition to fractional crystallization, such as late-stage parent body modification, possibly as a result of impacts, and subsequent metal-melt mixing, are required within the first 100 Myr of Solar System history to explain the range of HSE abundances.

10-Day Decitabine Versus Intensive Chemotherapy Followed By Transplantation in Fit AML Patients Aged ≥60 Years: Health-Related Quality of Life Outcomes of the Randomized Phase III Trial AML21 of the EORTC Leukemia Group, Gimema, Celg, and Gmds-SG

Background To assess the optimal treatment strategy for fit older patients with acute myeloid leukemia (AML), we performed a large international phase III randomized controlled trial (RCT) in fit AML patients aged >60 years, comparing 10-day decitabine (DEC) followed by allografting (HSCT) versus intensive chemotherapy (IC, "3+7" regimen) followed by HSCT. This trial revealed comparable HSCT rates and survival outcomes, but a more favorable safety profile with DEC when compared to IC (Lübbert M. et al, HemaSphere, 6, 26-27, 2022), supporting the hypothesis that reduced toxicity translates into a better health-related quality of life (HRQoL). Objective We hereby report the HRQoL outcomes of this international RCT. Patients and Methods HRQoL was a secondary endpoint and was assessed by the EORTC QLQ-C30 and its validated module for evaluating HRQoL in older patients, namely the EORTC QLQ-ELD14. Key inclusion criteria were: newly diagnosed AML, age >60 years, eligibility for IC, and a WHO performance status of ≤2. Assessments of HRQoL were performed at baseline and then at 2 (at regeneration after two treatment cycles), 6 and 12 months. For patients undergoing a HSCT, HRQoL was assessed prior to the procedure and at day 100 after the transplant. Quality of life deterioration (QD) was defined as any of the following events: death, progression, and clinically meaningful deterioration from baseline in at least one of the five pre-selected primary HRQoL scales (i.e., physical functioning, role functioning, fatigue, pain, and illness burden). The two co-primary endpoints were: QD at 2 months and QD at 6 or 12 months. A difference of 10 points or more was considered clinically meaningful. We hypothesized better HRQoL outcomes for patients treated with DEC. The changes in the primary HRQoL scales from baseline to 2 months and from baseline to the average of 6 and 12 months were secondary HRQoL endpoints. HRQoL trajectories of patients undergoing HSCT on-study based on evaluations at baseline, prior to HSCT and at day 100 after HSCT were also described. This study was registered at ClinicalTrials.gov (NCT02172872). Results Between December 2014 and August 2019, 606 patients were randomized and a baseline HRQoL assessment was available for 549 patients (91%): 279 out of 303 in the DEC arm and 270 out of 303 in the IC arm. Compliance among alive patients at 2, 6 and 12 months was 57%, 57%, and 64%, respectively. The proportion of patients evaluable for QD at 2 months was 60%. The proportion of patients evaluable for QD at 6 or 12 months was 82%. Analysis of the primary HRQoL endpoint showed that the proportion of patients deteriorating at 2 months was 76% (95% CI, 69 to 82%) in the DEC group vs 88% (95% CI, 82 to 93%) in the IC group (odds ratio 0.43 [95% CI, 0.24 to 0.76], P=.003). Several sensitivity analyses, using multiple imputation to deal with missing values and predefined modifications of the definition of QD, confirmed this finding. QD analysis at 6 or 12 months indicated no statistically significant difference between both arms (odds ratio 0.83 [95% CI, 0.46 to 1.52]). At 2 months from randomization, the illness burden scale increased by 4.19 (95% CI, -0.44 to 8.83) points in the DEC and by 15.15 (95% CI, 9.88 to 20.42) points in the IC arm, indicating a clinically meaningful and statistically significant difference of -10.96 (95% CI, -17.94 to -3.97), P=.004. The changes in the primary HRQoL scales from baseline to 2 months and from baseline to the average of 6 and 12 months are presented in Table 1. Baseline data were available for 218 of the 240 patients who received an on-study HSCT. Clinically meaningful HRQoL deteriorations between baseline and post-HSCT in the IC group were observed in all primary HRQoL scales except for pain. The change from baseline to post-HSCT HRQoL in the DEC arm appeared less pronounced and did not reach the threshold of clinical relevance. Conclusions Following two months of treatment, there was a significantly lower percentage of patients treated with DEC who reported HRQoL deterioration, compared to those treated with IC. Additionally, patients treated with DEC did not experience any clinically meaningful deterioration in key pre-specified HRQoL domains post-HSCT, while this was the case for patients treated with IC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cervical disc arthroplasty combined with two-level ACDF for the treatment of contiguous three-level cervical degenerative disc disease: A comparative study.

To compare the differences among constructs with one-level cervical disc arthroplasty (CDA) and two-level anterior cervical discectomy and fusion (ACDF).A retrospective study was conducted involving patients who underwent one-level CDA and two-level ACDF between June 2012 and July 2020. According to the different locations of CDA and ACDF, we divided the constructs into three types: type Ⅰa: CDA-ACDF-ACDF; type Ⅰb: ACDF-CDA-ACDF; type Ⅰc: ACDF-ACDF-CDA. The differences of clinical and radiological outcomes were evaluated.Fifty-three patients were included with 29 in type Ⅰa group, 11 in type Ⅰb group, and 13 in type Ⅰc group. After surgery, all groups showed significant improvement in apanese Orthopedic Association, Neck Disability Index, and Visual Analog Scale scores (p < 0.001). Range of motion(ROM) of the total cervical spine in type Ⅰc group decreased significantly compared with those in type Ⅰa and type Ⅰb groups (p < 0.05). No significant differences in ROM of the arthroplasty segment and the variations in ROM of the superior adjacent segment were observed among thethree groups. The fusion rates of the superior ACDF segments were significantly higher at 6 and 12 months postoperatively than those of the inferior ACDF segments (p < 0.05).The clinical outcomes were similar among constructs concerning different locations of CDA and ACDF in three-level hybrid surgery. ROM of the cervical spine in type Ⅰc group decreased significantly compared with that in type Ⅰa and type Ⅰb groups. The fusion rates of superior ACDF segments were higher at early time points after surgery than those of inferior ACDF segments.

Dietary Epidermal Growth Factor Supplementation Alleviates Intestinal Injury in Piglets with Intrauterine Growth Retardation via Reducing Oxidative Stress and Enhancing Intestinal Glucose Transport and Barrier Function.

Simple SummaryIt is well known that intrauterine growth retardation (IUGR) seriously affects the postnatal growth and intestinal health of piglets. Keeping intestinal health is of great importance to pig production. Numerous studies have shown that epidermal growth factor (EGF) has a positive effect on the repair of intestinal injury of animals. However, whether EGF can promote the intestinal health of IUGR piglets is unknown. Therefore, in our present study, a total of 12 IUGR piglets and 6 normal birth weight (NBW) piglets were selected to study the effects of EGF on the growth performance and intestinal health of IUGR piglets. Our study found that basal diet supplemented with 2 mg/kg EGF significantly improved the growth performance, jejunum morphology, jejunum glucose absorption and antioxidant capacity, and jejunum barrier function of piglets with IUGR. Therefore, this study confirmed that EGF has positive effects on the growth and intestinal development of piglets with IUGR.EGF plays an important role in the intestinal repair and nutrients transport of animals. However, the effect of EGF on the intestinal health of piglets with IUGR has not been reported. Thus, the present study was performed to investigate the effects of EGF on the intestinal morphology, glucose absorption, antioxidant capacity, and barrier function of piglets with IUGR. A total of 6 NBW piglets and 12 IUGR piglets were randomly divided into three treatments: NC group (NBW piglets fed with basal diet, n = 6), IC group (IUGR piglets fed with basal diet, n = 6), and IE group (IUGR piglets fed with basal diet supplemented with 2 mg/kg EGF, n = 6). Growth performance, serum biochemical profile, jejunum histomorphology, jejunum glucose absorption and antioxidant capacity, and jejunal barrier function were measured. The results showed that EGF supplementation significantly increased the final body weight (FBW), average daily gain (ADG), and average daily feed intake (ADFI) of piglets with IUGR; EGF supplementation significantly increased the total protein (TP), glucose (GLU), and immunoglobulin G (IgG) levels compared with the IUGR piglets in the IC group; EGF administration effectively exhibited an increased jejunum villus height (VH) and the villus-height-to-crypt-depth ratio (V/C) of IUGR piglets compared with the IC group; EGF supplementation significantly increased sodium/potassium-transporting adenosine triphosphatase (Na+/K+-ATPase) activity, intestinal alkaline phosphatase (AKP) activity, glucose transporter sodium/glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2), and AMP-activated protein kinase α1 (AMPK-α1) mRNA expressions in the jejunum of IUGR piglets compared with the IC group; EGF supplementation exhibited increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) levels, tended to increase glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and tended to decrease the malondialdehyde (MDA) level in the jejunum of IUGR piglets compared with the IC group; EGF supplementation significantly increased ZO-1, Claudin-1, Occludin, and MUC2 mRNA expressions and improved secreted immunoglobulin A (sIgA) secretion in the jejunum of IUGR piglets compared with the IC group and tended to decrease the interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) levels in the jejunum of IUGR piglets compared with the IC group. Pearson’s correlation analysis further showed that EGF can promote intestinal development and nutrient absorption by promoting intestinal barrier function, thus improving the growth performance of IUGR piglets.

Relationship between tongue pressure and handgrip strength: A systematic review and meta-analysis.

Muscle strength decreases with age, causing a decline in physical and oro-facial function. However, the impact of physiological and pathophysiological factors on tongue pressure (TP) has not been clarified. The purpose of this systematic review and meta-analysis was to compare and analyse TP and handgrip strength (HGS) between individuals aged <60 and ≥60 years, gender and need for care (independent older adults (IC) and older adults receiving nursing care (NC)). Furthermore, the effect of HGS in physical function on TP was examined. Human clinical studies reporting HGS and TP were searched systematically using PubMed and Ichushi-Web published from 1969 to Nov 2021. Random-effects meta-regressions were performed to compare between subgroups and to examine the association between HGS and TP (α < .05). Forty-four studies with a total of 10343 subjects were included. TP and HGS values were significantly higher in people aged <60 years relative to ≥60 years and in IC relative to NC (all p < .001). Regarding gender, there was no significant difference in TP (p=.370). However, a significant gender-dependent difference in TP was observed in people aged <60 years (p < .001), but not in aged ≥60 years in IC group (p=.118) and aged ≥60 years in NC group (p=.895). There was a significant positive correlation of HGS and TP (p < .001). Similar to decrease in HGS, age-related sarcopaenia seems to have an effect on oro-facial muscles like the tongue. Research on rehabilitation measures for oro-facial muscle strength, similar to HGS might be beneficial to improve the personally acquired oro-facial potential.