Trends in nutritional status and factors affecting prognostic nutritional index in ovarian cancer patients during chemotherapy: a prospective longitudinal study based on generalized estimating equations.

PURPOSE: Numerous studies have investigated the relationships between nutritional status and the prognosis of ovarian cancer (OC). However, the majority of these studies have focused on pre-chemotherapy malnutrition, with limited attention given to dynamic changes in nutritional status during chemotherapy and the associated risk factors affecting the prognostic nutritional index (PNI) in OC women. This study aims to explore the variation trend in the nutritional status of OC women over time during chemotherapy and assess its predictive factors. METHODS: A prospective longitudinal study was conducted from January 2021 to August 2023. Body mass index (BMI), PNI, Nutritional Risk Screening (NRS) 2002, serum albumin, and prealbumin measurements were utilized to assess the nutritional status of OC women. Data were collected through face-to-face interviews before initial chemotherapy (T0) and during the first (T1), third (T2), and fifth (T3) cycles of chemotherapy. Generalized Estimating Equations (GEE) were employed for the analysis of potential predictive factors. RESULTS: A total of 525 OC women undergoing chemotherapy completed the study. Significantly varied levels of BMI, PNI, and serum concentrations of hemoglobin, albumin, prealbumin, potassium, sodium, magnesium, and calcium were observed in these patients (p < 0.05). The prevalence of nutritional risk decreased over time during chemotherapy (p < 0.05). Nutritional parameters, including BMI, PNI, and the serum concentrations of albumin and prealbumin, exhibited an upward trend in nutritional status throughout the chemotherapy cycles (p < 0.05). Multivariate analysis indicated that higher levels of BMI, serum albumin, prealbumin, absolute lymphocyte count, and hemoglobin ≥ 110 g/L at admission were associated with elevated PNI after chemotherapy (ß = 0.077, p = 0.028; ß = 0.315, p < 0.001; ß = 0.009, p < 0.001; ß = 1.359, p < 0.001; ß = - 0.637, p = 0.005). CONCLUSION: Patients consistently demonstrated improvements in nutritional risk and status from the initiation to the completion of chemotherapy cycles. Nutritional monitoring of OC women, particularly those exhibiting abnormalities at the commencement of chemotherapy, is crucial. Targeted nutritional support programs should be developed to enhance the prognosis of OC women.

Protective effect of intranasal insulin on postoperative cognitive dysfunction in elderly patients with metabolic syndrome undergoing noncardiac surgery: a randomized clinical trial.

BACKGROUND: Insulin plays a crucial and multifactorial role in cognitive activity, with insulin resistance appearing in neurodegenerative and metabolic diseases. Insulin resistance contributes to the pathobiology of postoperative cognitive dysfunction (POCD) in experimental models, which can be rescued by intranasal insulin administration. AIMS: To test the effect of intranasal insulin on the incidence of POCD in elderly patients with metabolic syndrome. METHODS: The study was designed as a randomized, double-blind, placebo-controlled clinical trial. 116 elderly participants were randomly assigned to receive either 40 IU insulin (n = 58) or placebo (n = 58) for 7 days. The primary outcome was the incidence of POCD at 7 days and 3 months after surgery. Secondary outcomes included the degree of peripheral insulin resistance postoperatively, changes in peripheral inflammation levels and the safety of interventions. RESULTS: The results showed that POCD occurred in the insulin group on the 7th postoperative day in 11 (20.8%) patients, which was fewer than the 23 (45.1%) patients in the placebo group (P = 0.008). The insulin group indicated better cognitive functional performance on language and memory test than the placebo group (P < 0.05). Mean peripheral plasma concentration of TNF-α (P < 0.05) and CRP (P < 0.001) in the insulin group was significantly declined compared with the placebo group on D3 and D7. CONCLUSIONS: Intranasal insulin administration reduced the incidence of POCD and alleviated peripheral inflammatory levels in elderly patients with metabolic syndrome. TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR1800015502).

Analysis of spleen of mice (Mus musculus) infected with Aspergillus nidulans identifies immune-related genes.

Aspergillus nidulans (A. nidulans) is an ascomycetous fungus that can cause disseminated infection in humans or animals. The present study aimed to explore the pathogenesis and host spleen immune response after infection with A. nidulans. Thirty KM mice were divided into control group (C) and treated group (T). Serum was collected for the detection of inflammatory markers. Spleens were collected for histopathological examination, fungal culture and transcriptomic analysis. Compared with the control group, the concentrations of serum total protein (TP), globulin (GLO) and C-reactive protein (CRP) were significantly increased (P < 0.01), but the concentration of albumin (ALB) and the ratio of albumin/globulin (A/G) were significantly decreased in the treated group (P < 0.01). In addition, the splenic red pulp was hyperemic, and the white pulp was infiltrated by inflammatory cells in treated group. The chromatin was aggregated, and the mitochondria were swollen in the spleen lymphocytes of treated group. Transcriptome sequencing results showed that 47.2 million and 44.9 million clean reads were obtained in the control group and treated group, respectively. 946 differentially expressed genes (DEGs) were obtained, including 372 up-regulated genes and 574 down-regulated genes. GO analysis showed that these DEGs were mainly involved in the immune responses, antigen binding, immunoglobulin receptor binding, bacterial defence responses, endopeptidase activity and so on. Moreover, KEGG analysis showed that these DEGs were mainly enriched in the following pathways: complement and coagulation cascades, retinol metabolism, cytochrome p450, IL-17 signalling pathway and so on. Additionally, 9 DEGs was validated by qRT-PCR approach. In summary, this study revealed the immune response mechanism of spleen in A. nidulan-infected mice. It will benefit for a better understanding of the pathogenic mechanisms of A. nidulans.

ß-estradiol promotes the growth of primary human fetal spermatogonial stem cells via the induction of stem cell factor in Sertoli cells.

BACKGROUND: Mammalian spermatogenesis is responsible for male fertility and is supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs). Sertoli cells provide a supportive microenvironment for SSCs, in part by the production of stem cell factor (SCF), which is a potent regulator of spermatogonia proliferation and survival. METHODS: We investigated the novel role of ß-estradiol in modulating the proliferation and apoptosis of fetal SSCs via the regulation of SCF secretion in Sertoli cells isolated from human fetal testes. The proliferation of SSCs in the co-culture system was determined by colony formation and BrdU incorporation assays. TUNEL assay was used to measure SSC apoptosis in co-culture in response to treatment with control, ß-estradiol, or the combination of ß-estradiol and the estrogen receptor inhibitor ICI 182780. RESULTS: In the system with purified human fetal Sertoli cells (MIS+/c-Kit-/AP-), ß-estradiol upregulated the production of SCF in a dose- and time-dependent manner. In the co-culture system of primary human fetal SSCs (c-Kit+/SSEA-4+/Oct-4+/AP+) and Sertoli cells (MIS+), ß-estradiol markedly increased the proliferation of SSCs. Moreover, SSC apoptosis was significantly inhibited by ß-estradiol and was completely reversed by the combination of ß-estradiol and ICI 182780. CONCLUSION: Here we report, for the first time, that ß-estradiol can induce the increase of SCF expression in human fetal Sertoli cells and regulates the growth and survival of human fetal SSCs. These novel findings provide new perspectives on the current understanding of the role of estrogen in human spermatogenesis.

[HIV related risky behavioral network and molecular epidemiology of HIV seroconcordant couples in Taizhou municipality of Zhejiang Province].

UNLABELLED: Obstract: To characterize and analyze risky sexual networks and genetic scales to potential HIV transmission for HIV seroconcordant couples in Taizhou municipality of Zhejiang Province. METHODS: HIV seroconcordant positive couples were invited as index cases to participate in an egocentric survey on HIV related risky behavior and behavioral network prior to HIV diagnosis during 2008-2011. Within-couple HIV transmission pairs were determined by the combination of both behavioral and phylogenetic analysis. RESULTS: Totally 27 HIV seroconcordant couples were enrolled in this study. Male spouses were more likely to report having two or more sexual partners in the past years prior to HIV diagnosis than female spouses (88.9% vs. 37.0%). Among 27 couples, 20 couples including 17 couples by male but not female spouses, 3 couples by female but not male spouses reported having two or more sexual partners (i.e., multiple sexual partners) prior to HIV diagnosis; and 7 couples by both spouses reported having multiple sexual partners. Twenty four of 27 sexual networks were determined to be HIV transmission pairs (20) or potential transmission pairs (4), 3 couples were subtyped with discordant HIV subtypes or large genetic distance and thus had different sources of HIV transmissions. In addition, among 27 concordant couples, HIV drug resistance (HIVDR) or primary HIVDR existed in 6 ART-naïve participants in 4 networks; among them, 2 networks were determined to be potential HIVDR transmission couple pairs. CONCLUSIONS: The HIV strains isolated in HIV infected spouses characterized with diversity and CRF01_AE was the main strain subtype. One of the spouses with risky behavior infected HIV was the main route of transmission to other spouses through unprotected sexual contacts. HIVDR was isolated from some HIV infected individuals, suggesting the risk for HIVDR transmission in married couples. The results provide enhanced evidence for urgent development of tailored prevention strategies, such as couple-based HIV counseling and testing services to reduce HIV secondary transmission.

[Safety of the offspring conceived by assisted reproductive technology with cryopreserved donor sperm].

OBJECTIVE: To investigate the pregnancy outcomes of assisted reproductive technology (ART) with cryopreserved donor sperm and the safety of the offspring thus conceived. METHODS: The Human Sperm Bank of CITIC Xiangya Hospital provided cryopreserved donor semen to 31 reproductive centers in China between January 2006 and December 2012, with which 50247 ART cycles were accomplished. We compared the rates of birth defects and spontaneous abortion of intracervical insemination (ICI), intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). RESULTS: A total of 39 047 ART cycles were performed by artificial insemination with cryopreserved donor sperm, including 36 674 cycles of ICI and 2 372 cycles of IUI. Among the 8 612 clinical pregnancies achieved by ICI, there were 917 cases of spontaneous abortion (at <28 gestational wk) (10.6%) and 6133 live births, with 43 cases of birth defect (0.70%). Of the 547 clinical pregnancies achieved by IUI, there were 41 cases of spontaneous abortion (7.5%) and 426 live births, with 2 cases of birth defect (0.47%). Totally, 11 200 cycles of IVF and ICSI were accomplished with cryopreserved donor sperm. Of the 5 860 clinical pregnancies achieved by IVF, there were 456 cases of spontaneous abortion (7.8%) and 5089 live births, with 55 cases of birth defect (1.08%). Among the 350 clinical pregnancies achieved by ICSI, there were 30 cases of spontaneous abortion (8.6%) and 229 live births, with 3 cases of birth defect (1.31%). The birth defect rate of ART with cryopreserved donor sperm was significantly lower than that published by the Chinese Ministry of Health (0.86% vs 1.53%,P<0.01). CONCLUSIONS: The safety of the offspring conceived by ART with cryopreserved donor sperm is controllable.

Does Mandala Art Therapy Improve Psychological Well-Being of Gynecological Cancer Patients During the Perioperative Period? A Quasi-Experimental Study.

BACKGROUND: Women with gynecological cancer often experience psychological distress, particularly in response to surgical procedures. The impact of mandala art therapy (MAT) during the perioperative period for gynecological cancer patients remains uncertain. We aimed to examine the effects of the MAT program in women with gynecological cancer. METHODS: Employing a quasi-experimental design, we recruited 126 gynecological cancer patients from a university hospital through convenience sampling. Participants were assigned to either receive the MAT program or standard perioperative care. The interventions comprised a three-session MAT program guided by a team of trained mandala psychologists. Generalized estimating equations (GEE) were employed to analyze the effects of MAT over time. RESULTS: A total of 126 patients were enrolled, and 118 completed the entire study. Over 90% of participants completed the perioperative MAT interventions, reporting relatively high satisfaction with the program (7.70 out of 10). Individuals in the MAT group exhibited improved therapeutic effects on STAI-S, VASS, and vital signs over time. Notably, significant group*time interaction effects were noted in STAI-S scores at both the first evaluation, T1 (ß = -4.220, P < .005) and the third evaluation, T3 (ß = -3.797, P < .05), and VASS scores at T1 (ß = -11.186, P < .005), T2 (ß = -9.915, P < .05) and T3 (ß = -9.831, P < .05). Regarding vital signs, the multivariate GEE model revealed significant interaction effects in systolic blood pressure values at both T1 (ß = -7.102, P < .05) and T3 (ß = -10.051, P < .005), diastolic blood pressure values at T3 (ß = -6.441, P < .005), and pulse values at T1 (ß = -6.085, P < .005). No significant differences were observed between groups for pain, hope, or self-acceptance. CONCLUSION: This study posited that MAT could serve as a valuable complementary approach in perioperative care for addressing the psychological needs of women with gynecological cancer. Subsequent research employing more robust methodologies and larger, more diverse participant samples will be necessary to validate these conclusions.

Insulin resistance and osteocalcin associate with the incidence and severity of postoperative delirium in elderly patients undergoing joint replacement.

AIM: While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains unclear. This study aimed to investigate the association between POD and indicators of insulin sensitivity, including insulin resistance and osteocalcin. METHODS: A total of 120 elderly patients undergoing joint replacement were recruited and divided into delirium and non-delirium groups. Plasma and cerebrospinal fluid (CSF) samples were collected for the analysis of biomarkers, including insulin, uncarboxylated osteocalcin (ucOC), total osteocalcin (tOC), and glucose. Insulin resistance was assessed through the homeostatic model assessment of insulin resistance (HOMA-IR). MAIN RESULTS: Out of the total, 28 patients (23.3%) experienced POD within 5 days after surgery. Patients with delirium exhibited higher levels of preoperative HOMA-IR and ucOC in CSF and plasma, and of tOC in CSF (P = 0.028, P < 0.001, P = 0.005, P = 0.019). After adjusting for variables, including age, Mini-Mental State Examination score, surgical site and preoperative fracture, only preoperative ucOC in CSF and HOMA-IR were significantly linked to the incidence of delirium (OR = 5.940, P = 0.008; OR = 1.208, P = 0.046, respectively), both of which also correlated with the severity of delirium (P = 0.007, P < 0.001). Receiver operating curve analysis indicated that preoperative HOMA-IR and ucOC in CSF might partly predict POD (area under the curve [AUC] = 0.697, 95% confidence interval [CI] = 0.501-0.775, AUC = 0.745, 95% CI = 0.659-0.860). CONCLUSIONS: We observed that preoperative elevated HOMA-IR and ucOC in CSF were associated with the incidence and severity of POD. While these preliminary results need confirmation, they suggest a potential involvement of insulin resistance and osteocalcin in the pathological mechanism of POD. Geriatr Gerontol Int 2024; 24: 421-429.

Performance of a modified RBC system in simulated municipal wastewater treatment.

A new method based on rotating biological contactor (RBC) was employed for solving the problems of long hydraulic retention times (HRT) low specific surface area and organic loading rates (OLR) in conventional RBCs. The system showed its particular adsorption ability of microorganisms in the biofilm-attaching period. Microbes on the first cage were observed in comparison with the second one. Packing biodisc also had a good shock load tolerance. It was observed that the system performance improved at higher HRTs, while at the increased level of input OLR, the removal performance worsened slightly. The positive role of rotational speed in the treatment of municipal wastewater was more pronounced in the range of 10-12 rpm. Chemical oxygen demand (COD) removal rate achieved 94% under the optimal operating conditions, which were HRT of 1.5 h, rotational speed of 9.9 rpm. The modified RBC system is highly beneficial to engineering application for better system performance and lower energy consumption.

DFT study of common anions adsorption at graphene surface due to anion-π interaction.

Using density functional theory (DFT) calculations, we researched the different anions adsorption on the graphene and found that anions can be stably adsorbed on the graphene surface due to the anion-π interaction. The adsorption energy decreased as the order of HPO42- > SO42- > F- > CH3COO- > ClO3- > NO3- > ClO4- > SCN- > Cl- > Br-. The adsorption energy markedly increased as the valence of anion increased from negative monovalence (< -20 kcal/mol) to negative bivalence (> -40 kcal/mol). The energy decomposition analysis (EDA) showed that anion-π interaction is mainly induced by orbital effect. This work provides new insights for understanding Hofmeister effect at graphene interface from the molecular level and indicates that the anion-π interaction cannot be ignored at the interface, especially for the substrate with π-electron-rich carbon-based nanomaterials.

Effectiveness of Bone Marrow-Derived Platelet-Rich Fibrin on Rotator Cuff Healing in a Rabbit Degenerative Model.

BACKGROUND: Platelet-rich fibrin (PRF) is a second-generation platelet concentrate. Although peripheral blood-derived PRF (P-PRF) is commonly applied in biological augmentation, there is no report about the therapeutic effect of bone marrow-derived PRF (BM-PRF) for degenerative rotator cuff tears (RCTs). PURPOSE/HYPOTHESIS: To examine the effects of platelet-rich plasma (PRP), P-PRF, and BM-PRF during rotator cuff repair (RCR) in degenerative RCTs in rabbits. We hypothesized that BM-PRF would accelerate the bone-tendon healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: Degenerative RCT models were created 2 weeks before beginning the study, and 68 juvenile rabbits were divided into 4 groups: the control, PRP, P-PRF, and BM-PRF groups. RCR without augmentation was done in the control group. PRP was prepared by centrifuging peripheral blood twice using a plastic tube. P-PRF and BM-PRF were prepared by centrifuging peripheral blood and bone marrow, respectively, using a glass tube. Rabbits from PRP, P-PRF, and BM-PRF groups were administered the augmentation in a similar fashion for RCR, between the rotator cuff and the footprint of the humerus. At 4, 8, and 12 weeks, rabbits were euthanized and histologically assessed using hematoxylin and eosin staining, Alcian blue staining, and immunohistochemical staining for type I and III collagen. The sections were also evaluated with immunofluorescence staining of vascular endothelial growth factor (VEGF) at 4 weeks. RESULTS: The continuity was significantly better in the BM-PRF group at 4 weeks (P < .05). Immunofluorescence staining demonstrated that VEGF-positive stained cells were significantly greater in the BM-PRF group than in the control group (P < .01). The modified tendon maturing score was significantly greater in the BM-PRF group than in the control and PRP groups at 12 weeks (P < .05). There was no significant difference in the modified tendon maturing score of the P-PRF group compared with the control group. CONCLUSION: The rabbit model of degenerative RCTs demonstrated that RCR combined with BM-PRF enhanced tendon-bone continuity and increased the VEGF-positive cells at 4 weeks and obtained preferable tendon-bone maturation at 12 weeks. CLINICAL RELEVANCE: RCR augmented with BM-PRF has the potential to improve clinical outcomes for RCTs.

Cardio- and Cerebrovascular Outcomes of Postoperative Acute Kidney Injury in Noncardiac Surgical Patients With Hypertension.

Background: The cardiovascular and cerebrovascular risk of postoperative acute kidney injury (AKI) in surgical patients is poorly described, especially in the hypertensive population. Methods: We conducted a retrospective cohort study among all hypertensive patients who underwent elective noncardiac surgery from January 1st, 2012 to August 1st, 2017 at the Third Xiangya Hospital. The primary outcomes were fatal stroke and fatal myocardial infarction (MI). The secondary outcomes were all-cause mortality. Results: The postoperative cumulative mortality within 3 months, 6 months, 1 year, 2 years, and 5 years were 1.27, 1.48, 2.15, 2.15, and 5.36%, for fatal stroke, and 2.05, 2.27, 2.70, 3.37, and 5.61% for fatal MI, respectively, in patients with postoperative AKI. Compared with non-AKI patients, those with postoperative AKI had a significantly higher risk of fatal stroke and fatal MI within 3 months [hazard ratio (HR): 5.49 (95% CI: 1.88-16.00) and 11.82 (95% CI: 4.56-30.62), respectively], 6 months [HR: 3.58 (95% CI: 1.43-8.97) and 9.23 (95% CI: 3.89-21.90), respectively], 1 year [HR: 3.64 (95% CI: 1.63-8.10) and 5.14 (95% CI: 2.50-10.57), respectively], 2 years [HR: 2.21 (95% CI: 1.03-4.72) and 3.06 (95% CI: 1.66-5.64), respectively], and 5 years [HR: 2.27 (95% CI: 1.30-3.98) and 1.98 (95% CI: 1.16-3.20), respectively]. In subgroup analysis of perioperative blood pressure (BP) lowering administration, postoperative AKI was significantly associated with 1-year and 5-year risk of fatal stroke [HR: 9.46 (95% CI: 2.85-31.40) and 3.88 (95% CI: 1.67-9.01), respectively] in patients with ACEI/ARB, and MI [HR: 6.62 (95% CI: 2.23-19.62) and 2.44 (95% CI: 1.22-4.90), respectively] in patients with CCB. Conclusion: Hypertensive patients with postoperative AKI have a significantly higher risk of fatal stroke and fatal MI, as well as all-cause mortality, within 5 years after elective noncardiac surgery. In patients with perioperative administration of ACEI/ARB and CCB, postoperative AKI was significantly associated with higher risk of fatal stroke and MI, respectively.

Efficacy Analysis of Day Surgery A1 Pulley Release for Pediatric Trigger Thumb.

Objective: To investigate clinical application of day surgery A1 pulley release for pediatric trigger thumb. Methods: We retrospectively analyzed the clinical data of 1,642 children with trigger thumb who were treated with day surgery A1 pulley release at our hospital, including satisfaction surveys, functional recovery, and complications. Results: The operative time for unilateral and bilateral tenolysis was 4.8 ± 3.1 and 9.2 ± 3.8 min, respectively. Three children had postoperative fever and were discharged on the 2nd day after surgery. The rest of the children were discharged on the day of surgery. All incisions healed primarily, and no complications of vascular and nerve injury were reported. The patients' degree of satisfaction with the medical treatment process, diagnosis and treatment workflow, treatment effectiveness, length of hospital stay and hospitalization cost, and discharge guidance were 97.9, 96.1, 99.3, 91.1, and 98.5%, respectively. The follow-up period was between 5 months and 3 years and 1 month. Four children experienced symptom relapse after the operation, and re-tenolysis was performed in one of them. At the final follow-up, the appearance and function of the thumb had recovered well in all cases. Conclusion: Day surgery A1 pulley release can effectively release tendon sheaths and has a short operative time, no complications of vascular and nerve injury, and good recovery of thumb function. It is a safe and reliable procedure with high patient satisfaction, and it is worthy of clinical promotion.

Gait characteristics and effects of the cerebrospinal fluid tap test in probable idiopathic normal pressure hydrocephalus.

OBJECTIVES: To evaluate gait characteristics and investigate changes pre- and post- cerebrospinal fluid tap test (CSF TT) in gait parameters in patients with probable idiopathic normal pressure hydrocephalus (iNPH). METHODS: Sixty patients were sequential circuited and diagnosed with possible iNPH according to Japanese second iNPH guidelines at our hospital from December 2016 to March 2021. All patients underwent the CSF TT. Gait parameters, cognitive and urinary function were assessed pre- and post-CSF TT. Patients who were unable to ambulate to take the tests or could not walk independently or walked normally were excluded. RESULTS: Twenty-six patients were diagnosed with probable iNPH using the CSF TT. After CSF TT, the Boon sum score improved from 20.0 ± 7.7-16.6 ± 8.0 (p < 0.001), the Boon walking score improved from 8.9 ± 3.5-7.8 ± 4.4 (p = 0.008), the Boon step score improved from 6.3 ± 2.3-5.2 ± 2.1 (p < 0.001), the Boon time score improved from 4.9 ± 2.4-3.7 ± 2.3 (p < 0.001), tandem walking disturbance improved from 1.7 ± 0.7-1.4 ± 0.9 (p = 0.043), tendency toward falling improved from 1.7 ± 0.7-1.3 ± 1(p = 0.022), 3-meter timed up and go test (3-mTUG) improved from 21.9 ± 7.1-17.6 ± 5.1( p < 0.001), 10-meter walking (10-MWT) step improved from 31.1 ± 13.1-24.6 ± 7.5 (p < 0.001), velocity improved from 0.7 ± 0.2-0.8 ± 0.3 (p < 0.001) and stride length improved from 0.4 ± 0.1-0.46 ± 0.1(p < 0.001), compared with before the CSF TT. CONCLUSION: These results suggest that many parameters in the Boon gait test were responsive to the CSF TT, and the Boon gait test may help objectify response to the CSF TT by combining the 10-MWT and 3-mTUG gait assessments.

C21, C22 pregnane glycosides and cytotoxic C27 spriostanol steroids from Asparagus cochinchinesis.

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C21 (1-4) and one new pregnane (5) glycosides, and four known C27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC50 values of 35.5 and 39.6 µM, respectively.

Identification of mRNA Prognostic Markers for TGCT by Integration of Co-Expression and CeRNA Network.

Testicular germ cell tumor (TGCT) is the most common malignant tumor in young men and is associated with poor prognosis. We assessed the RNA expression profiles of 13 TGCT tissues and 4 adjacent normal tissues by transcriptome sequencing to identify novel prognostic biomarkers. We detected several differentially expressed mRNAs in TGCT that were functionally annotated by GO and KEGG enrichment analyses to tumorigenesis-related processes such as immunity and chemotherapeutic resistance. An mRNA-lncRNA-miRNA regulatory network was constructed using RNA-Seq data and public databases, and integrated with TCGA database to develop a prediction model for metastasis and recurrence. Finally, GRK4, PCYT2 and RGSL1 were identified as predictive markers of survival and therapeutic response. In conclusion, we found several potential predictors for TGCT prognosis and immunotherapeutic response by ceRNA network analysis.

TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL.

Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.

Individual mortality risk predictive system of patients with acute-on-chronic liver failure based on a random survival forest model.

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS: The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.

[Simultaneous discriminating measurement of temperature and strain based on a long period grating's spectrum].

The new scheme of using a long period grating for simultaneous discriminating measurement of temperature and strain is proposed. The scheme is based on the long period grating's spectrum characteristics. The spectrum is composed of multiple and different loss peak. The resonant wavelength of the first and fourth-order loss peak with different temperature and strain sensitivity was selected in this experiment. The wavelength shift resulting from parameter variation can be obtained by observing its corresponding spectrum. The temperature was acquired by a study on the temperature characteristic of a LPG. The strain sensitivity was obtained by the research on the strain characteristic of a LPG. The standard matrix equation was set up and solved according to the corresponding parameter. The authors know by calculating the standard matrix equation that the cross-sensitivity has little influence on the measurement of the parameter. As the effect of cross-sensitivity is lower than the resolution of the LPG in this case, we can eliminate the deviation due to the cross-sensitive by appropriate compensation. The errors of temperature and strain were calculated to be +/- 0.92 degrees C and +/- 22 microepsilon respectively. The cross-sensitivity between temperature and strain was decreased and the measuring precision of the system was improved by using this scheme in which a single long period grating was used to test two measurands. By comparison between the applied and the calculated temperature and strain of a LPG, the experiment results showed that the methods are feasible. The experimental system is small and the cost is relatively low. The experimental device is simple and practical and has good application prospect.

Methionine increases yolk production to offset the negative effect of caloric restriction on reproduction without affecting longevity in C. elegans.

Caloric restriction (CR) or Dietary restriction (DR) is known to improve health and in many cases increases lifespan. However, its negative effect on reproduction has not been fully studied. Practicing CR/DR without adequate knowledge on its side effect may risk complications such as infertility, birth defect, or malnutrition. In this study, by using several CR strategies in C. elegans, we examine key functions of reproduction including embryonic development and larvae growth. We find that CR significantly decreases the survival of embryos and slows the growth of the offspring. We further determine that defect in oocyte but not sperm is responsible for the compromised reproduction under CR. Interestingly, adding methionine to the medium reverses the reproduction defects, but does not affect the long lifespan resulted from CR. The beneficial effect of methionine on reproduction requires the yolk protein vitellogenin. CR down-regulates vitellogenin expression, which can be reversed by supplementing methionine in the food. Lacking the yolk protein transport due to rme-2 mutation blocks methionine's beneficial effects. Our study has revealed a novel, methionine-mediated genetic pathway linking nutrient sensing to reproduction and suggested methionine as a potential food supplement to mitigate the side effect of CR.