A study on improving cancer-related fatigue and disease-related psychological variables in patients with cervical cancer based on online mindfulness-based stress reduction: a randomized controlled trial.

BACKGROUND: The persistent destructive power of cancer-related fatigue (CRF) has been regarded as the biggest influencing factor affecting the postoperative physical and mental health of patients with cervical cancer. During this process, patients might also experience different feelings of disease-related psychological. Therefore, this study aimed to adopt mindfulness-based stress reduction (MBSR) to intervene in patients with cervical cancer, and conducted follow-up for 3 and 6 months to observe the effects of changes in CRF, uncertainty in illness, coping styles, sense of coherence (SOC), and perceived social support (PSS). METHODS: A randomized controlled trial was conducted in ShengJing Hospital of China Medical University. A total of 102 patients were selected, and 78 patients completed the whole process, including 40 in the experimental group and 38 in the control group. Data were collected according to Cancer Fatigue Scale, Medical Coping Modes Questionnaire, Multidimensional Scale of Perceived Social Support, and Sense of Coherence-13. The change trend and difference of the two groups of research data were compared by repeated measurement analysis of variance. Bonferroni test was used for multiple tests between groups. RESULTS: The CRF, SOC, and coping styles of the MBSR group showed a decreasing trend (P < 0.001) at after MBSR, 3 months follow-up, and 6 months follow-up compared to the before MBSR. However, the uncertainty in illness of the MBSR group showed a decreasing trend (P < 0.001) at after MBSR compared to the before MBSR, and it rose in 3 months follow-up and 6 months follow-up. CONCLUSION: MBSR can effectively alleviate the fatigue of CRF after treatment, while improving their psychological environment. Medical workers can consider implementing online MBSR for patients with cervical cancer in their daily rehabilitation nursing, which is beneficial for their recovery. TRIAL REGISTRATION: China Clinical Trial Registration Center ChiCTR2000040122 (https//www.chictr.org.cn/). Registered on November 21, 2020.

Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation.

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.

Long noncoding RNA VPS9D1-AS1 promotes the progression of endometrial cancer via regulation of the miR-187-3p/S100A4 axis.

VPS9D1-AS1 functions as an oncogene in many cancers. However, its role and potential mechanism in the progression of endometrial cancer (EC) are not fully understood. VPS9D1-AS1 levels in EC and adjacent normal tissues were investigated using the TCGA-UCEC cohort and 24 paired clinical samples. The roles of VPS9D1-AS1 and miR-187-3p in cell cycle, proliferation, and apoptosis were evaluated by loss- and gain-of-function experiments. In addition, the effect of VPS9D1-AS1 on tumor growth was further investigated in vivo. Rescue experiments were performed to investigate the involvement of the miR-187-3p/S100A4 axis in VPS9D1-AS1 knockdown-mediated antitumor effects. VPS9D1-AS1 was highly expressed in EC tissues. VPS9D1-AS1 knockdown, similar to miR-187-3p overexpression, significantly inhibited cell proliferation, inhibited colony formation, induced cell cycle arrest, and facilitated apoptosis of KLE cells. MiR-187-3p bound directly to VPS9D1-AS1 and the 3'UTR of S100A4. Furthermore, VPS9D1-AS1 negatively regulated miR-187-3p while positively regulating S100A4 expression in EC cells. MiR-187-3p knockdown or S100A4 overexpression partially reversed the tumor suppressive function of VPS9D1-AS1 knockdown. The results suggest that VPS9D1-AS1 affects EC progression by regulating the miR-187-3p/S100A4 axis. This may provide a promising therapeutic target to help treat EC.

Molecular network characteristics and drug resistance analysis of 392 newly reported MSM HIV/AIDS cases in Chongqing, China.

To comprehensively investigate the molecular transmission patterns of HIV-1 genotypes among men who have sex with men (MSM) in Chongqing, we employed 392 pol sequences of MSM to construct a phylogenetic tree and gene transmission network. Among the viral subtypes, CRF07_BC accounted for 73.2% (287/392) and CRF01_AE accounted for 20.7% (81/392), emerging as the predominant subtypes in this investigation. Additionally, we observed the presence of CRF55_01B, subtype B, CRF08_BC and other circulating recombinant forms. The HIV-1 molecular network was constructed with a gene distance threshold of 1.5%, resulting in an entry rate of 61.4% (241/392). Within the network, we identified a total of 23 molecular clusters, with the largest cluster being the CRF07_BC molecular cluster comprising 148 node values. Transmitted drug-resistance (TDR) mutations were found in 4.34% of the cases, with 1.79% associated with protease inhibitors (PIs), 0.51% with nucleoside reverse transcriptase inhibitors (NRTIs), and 2.55% with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Statistical analysis indicated a higher enrollment rate in the HIV-1 molecular network among infected individuals with the CRF07_BC subtype, those identifying with same-sex sexual roles as "vers," and individuals with higher education levels. This suggests the need for strengthened investigation and intervention in this population to prevent the formation of larger transmission clusters. Furthermore, continuous monitoring of the HIV-1 molecular dynamics network is necessary to promptly and accurately track changes in molecular epidemic characteristics.

Long-Term Risks of Cardiovascular Death among Older Patients with Major Hematological Malignancies: A Population-Based Cohort Study from SEER Database.

BACKGROUND: The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM). METHODS: This study included 103,102 older patients diagnosed with seven major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result database. The proportion of deaths, Fine-Gray subdistribution hazards regression model, standardized mortality ratios (SMR), and absolute excess risk (AER) were used to evaluate the risk of CVD-related death. RESULTS: For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular disease-related deaths (SMR: 0.99-1.66; AER: -0.35 to 24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in patients with Hodgkin lymphoma with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types. CONCLUSIONS: For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy. IMPACT: Our results emphasize the need to manage long-term cardiovascular risk in older patients with hematological malignancies, especially in those identified as high-risk cases.

The value of transitory protective stomas during primary debulking surgery for advanced epithelial ovarian cancer-- a retrospective cohort study.

OBJECTIVES: Limited data are available on patients with advanced-stage epithelial ovarian cancer (OC) who require ostomy during primary cytoreductive surgery. This study aimed to investigate the application of postoperative and long-term oncological results from transitory protective stoma (TPS) formation during primary debulking surgery (PDS) for OC. METHODS: This is a retrospective cohort study with a single center. We identified patients with stage III-IV OC who underwent colon resection and anastomosis. Depending on the methods used after colorectal anastomosis and the outcomes of surgical resection, the patients were stratified into three groups: resection and end-to-end anastomosis, resection and ostomy, or R1 resection. Demographic and clinical data were analyzed. RESULTS: 84 patients underwent colorectal resection during cytoreduction for FIGO stage III-IV OC. Patients undergoing ostomy were more likely to have a longer mean operative time (266 vs. 283 vs. 236 min; P=0.003) and to undergo rectosigmoid resection at the time of cytoreductive surgery (56.0% vs. 22.7%, P=0.007). Their postoperative feeding (7 vs. 1 vs. 3 d, P<0.001) and exhaustion (6 vs. 3 vs. 3, P<0.001) times were similar to those of patients with R1 resection and much earlier than those of patients with intestinal anastomosis. The first normal time (35 d) and half-life (14.68 d) of CA125 after surgery were significantly better in patients with TPS group. The overall incidence of complications was the same, and there was no significant difference in the 30-day readmission rate. The overall quality of life assessment was significantly lower in the R1 resection group. CONCLUSIONS: TPSs can accelerate postoperative recovery and the initiation of postoperative chemotherapy, reduce the risk of mortality and disease progression and limit the incidence of complications.

Electroacupuncture regulates histone acetylation of Bcl-2 and Caspase-3 genes to improve ischemic stroke injury.

Background: Imbalances between Bcl-2 and caspase-3 are significant evidence of apoptosis, which is considered an influential factor in rapidly occurring neuronal cell death and the decline of neurological function after stroke. Studies have shown that acupuncture can reduce poststroke brain cell damage via either an increase in Bcl-2 or a reduction in caspase-3 exposure. The current study aimed to investigate whether acupuncture could modulate Bcl-2 and caspase-3 expression through histone acetylation modifications, which could potentially serve as a neuroprotective mechanism. Methods: This study used TTC staining, Nissl staining, Clark neurological system score, and Evans Blue (EB) extravasation to evaluate neurological damage following stroke. The expression of Bcl-2/caspase-3 mRNA was detected by real-time fluorescence quantification of PCR (real-time PCR), whereas the protein expression levels of Bcl-2, Bax, caspase-3, and cleaved caspase-3 were assessed using western blotting. TUNEL staining of the ischemic cortical neurons determined apoptosis in the ischemic cortex. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities, along with the protein performance of AceH3, H3K9ace, and H3K27ace, were detected to evaluate the degree of histone acetylation. The acetylation enrichment levels of H3K9 and K3K27 in the Bcl-2/caspase-3 gene were assessed using Chromatin Immunoprecipitation (ChIP) assay. Results: Our data demonstrated that electroacupuncture (EA) exerts a significant neuroprotective effect in middle cerebral artery occlusion (MCAO) rats, as evidenced by a reduction in infarct volume, neuronal damage, Blood-Brain Barrier (BBB) disruption, and decreased apoptosis of ischemic cortical neurons. EA treatment can promote the mRNA and protein expression of the Bcl-2 gene in the ischemic brain while reducing the mRNA and protein expression levels of caspase-3 and effectively decreasing the protein expression levels of Bax and cleaved caspase-3. More importantly, EA treatment enhanced the level of histone acetylation, including Ace-H3, H3K9ace, and H3K27ace, significantly enhanced the occupancy of H3K9ace/H3K27ace at the Bcl-2 promoter, and reduced the enrichment of H3K9ace and H3K27ace at the caspase-3 promoter. However, the Histone Acetyltransferase inhibitor (HATi) treatment reversed these effects. Conclusions: Our data demonstrated that EA mediated the expression levels of Bcl-2 and caspase-3 in MCAO rats by regulating the occupancy of acetylated H3K9/H3K27 at the promoters of these two genes, thus exerting a cerebral protective effect in ischemic reperfusion (I/R) injury.

Indications affect neonatal outcomes following early rescue ICSI: a retrospective study.

PURPOSE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients. CONCLUSION: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.

High-efficiency electrocatalytic nitrite-to-ammonia conversion on molybdenum doped cobalt oxide nanoarray at ambient conditions.

Electrochemical conversion of nitrite (NO2-) contaminant to green ammonia (NH3) is a promising approach to achieve the nitrogen cycle. The slow kinetics of the complex multi-reaction process remains a serious issue, and there is still a need to design highly effective and selective catalysts. Herein, we report that molybdenum doped cobalt oxide nanoarray on titanium mesh (Mo-Co3O4/TM) acts as a catalyst to facilitate electroreduction of NO2- to NH3. Such a catalyst delivers an extremely high Faradaic efficiency of 96.9 % and a corresponding NH3 yield of 651.5 µmol h-1 cm-2 at -0.5 V with strong stability. Density functional theory calculations reveal that the introduction of Mo can induce the redistribution of electrons around Co atoms and further strengthen the adsorption of NO2-, which is the key to facilitating the catalytic performance. Furthermore, the assembled battery based on Mo-Co3O4/TM suggests its practical application value.

Does cleavage stage morphology increase the discriminatory power of prediction in blastocyst transfer outcome?

PURPOSE: To evaluate the contribution of the cleavage stage morphological parameters to the prediction of blastocyst transfer outcomes. METHODS: A retrospective study was conducted on 8383 single-blastocyst transfer cycles including 2246 fresh and 6137 vitrified-warmed cycles. XGboost, LASSO, and GLM algorithms were employed to establish models for assessing the predictive value of the cleavage stage morphological parameters in transfer outcomes. Four models were developed using each algorithm: all-in model with or without day 3 morphology and embryo quality-only model with or without day 3 morphology. RESULTS: The live birth rate was 48.04% in the overall cohort. The AUCs of the models with the algorithm of XGboost were 0.83, 0.82, 0.63, and 0.60; with LASSO were 0.66, 0.66, 0.61, and 0.60; and with GLM were 0.66, 0.66, 0.61, and 0.60 respectively. In models 1 and 2, female age, basal FSH, peak E2, endometrial thickness, and female BMI were the top five critical features for predicting live birth; In models 3 and 4, the most crucial factor was blastocyst formation on D5 rather than D6. In model 3, incorporating cleavage stage morphology, including early cleavage, D3 cell number, and fragmentation, was significantly associated with successful live birth. Additionally, the live birth rates for blastocysts derived from on-time, slow, and fast D3 embryos were 49.7%, 39.5%, and 52%, respectively. CONCLUSIONS: The value of cleavage stage morphological parameters in predicting the live birth outcome of single blastocyst transfer is limited.

Characteristics of Electroacupuncture Preconditioning and Treatment on Regulation of the Brain Transcriptome in Rats with Ischemic Stroke.

BACKGROUND: Accumulating evidence suggests that acupuncture may serve as a potent strategy to mitigate the deleterious effects of ischemic stroke on neural tissue. The present investigation delineated the neuroprotective potential of electroacupuncture (EA) administered pre-and post-stroke, with a focus on determining the commonalities and disparities between these two therapeutic approaches in ameliorating ischemic stroke-induced brain injury. The ultimate objective is to inform optimal timing for acupuncture intervention in the clinical management and prevention of stroke. METHODS: The extent of cerebral infarction was quantified with 2,3,5-triphenyltetrazolium chloride staining. The integrity of the blood-brain barrier was assessed by evaluating the extravasation of Evans blue (EB) dye, while neurological function was appraised using the Longa neurological scoring system. RNA sequencing was employed to examine the transcriptomic landscape of ischemic brain tissue, with subsequent bioinformatics annotation of the sequencing data facilitated by Metascape. RESULTS: (1) A notable decrease in the ischemic infarct volume was observed in both the EA-preconditioned plus middle cerebral artery occlusion (MCAO), EA-preconditioned plus middle cerebral artery occlusion (EAM) and MCAO plus EA-treated (MEA) groups, compared to the MCAO group. Furthermore, the decreased leakage of EB and reduction in neurological function impairment scores were evident in the EAM and MEA groups compared with the MCAO group. (2) Relative to the Sham group, the MCAO group exhibited a total of 4798 differentially expressed genes (DEGs), with 67.84% demonstrating an expression fold change (FC) greater than 1.5, and 34.16% exceeding a FC of 2. The EAM and MEA groups displayed 4020 and 1956 DEGs, respectively, compared to the MCAO group. In both groups, more than 55% of DEGs showed an expression FC surpassing 1.5, whereas only approximately 10% exhibited a change greater than 2-fold. Remarkably, EA preconditioning and EA treatment resulted in the reversal of 18.72% and 28.91% of DEGs, respectively, in the MCAO group. (3) The DEGs upregulated in response to ischemic stroke were predominantly implicated in immune inflammatory processes and cellular apoptosis, whereas the downregulated DEGs were associated with neurogenesis and neuronal signal transduction. The MEA-induced upregulated DEGs were primarily involved in neural transmission and metabolic processes, whereas the downregulated DEGs were linked to excessive inflammatory responses to physical and chemical stimuli, as well as cell matrix adhesion chemotaxis. In the context of EAM, the upregulated DEGs were chiefly related to protein biosynthesis, and energy and metabolic processes, whereas the downregulated genes were connected to gene transcriptional activity, synaptic function, and neuronal architecture. CONCLUSIONS: Both preconditioning and post-event treatment with acupuncture demonstrated efficacy in mitigating pathological damage to brain tissue in a rat model of ischemic stroke, albeit with some divergences in their gene targets. The integration of EA preconditioning and treatment may potentially confer enhanced neuroprotection in the clinical management of stroke patients.

STAT3 modulates CD4+ T mitochondrial dynamics and function in aging.

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production.

Analysis of clinicopathological features and prognosis of double primary cervical cancer and ovarian cancer based on SEER database.

OBJECTIVE: Double primary cervical cancer and ovarian cancer refer to the simultaneous or successive appearance of cervical cancer and ovarian cancer in the same patient. Due to the low incidence, there are few relevant reports. Therefore, this study is the first population-based analysis of the clinicopathological features as well as the prognostic status of double primary cervical cancer and ovarian cancer. We look forward to providing a reference for future clinical diagnosis and treatment. METHODS: In this study, 473 cases of double primary cervical cancer and ovarian cancer were collected from 1975 to 2019 through the SEER database. Double primary cancers were considered non-synchronous when they were diagnosed more than 6 months apart and were classified as Group A. Double primary cancers were considered synchronous when the interval between diagnosis of the two tumors was less than or equal to 6 months and was classified as group B. RESULTS: In this study, the incidence of double primary cervical cancer and ovarian cancer accounted for 0.39% of primary cervical cancer and 0.24% of primary ovarian cancer in the same period. 80% of patients developed second cancer within 107 months of their first cancer being diagnosed. Compared with non-synchronous cancer, synchronous cancer is mainly characterized by simultaneous bilateral ovarian involvement and early clinical stage, but highly malignant, high lymph node metastasis rate, and poor prognosis. CONCLUSION: Most patients developed second cancer within 107 months of their first cancer being diagnosed. Age at diagnosis, bilateral ovarian invasion, the interval between diagnoses, pathological type and stage of ovarian cancer, and grade of cervical cancer are important factors affecting survival, which still needs to be confirmed by more extensive studies in future.

High-Performance Electrocatalytic Reduction of Nitrite to Ammonia under Ambient Conditions on a FeP@TiO2 Nanoribbon Array.

Electrochemical nitrite (NO2-) reduction is recognized as a promising strategy for synthesizing valuable ammonia (NH3) and degrading NO2- pollutants in wastewater. The six-electron process for the NO2- reduction reaction is complex and necessitates a highly selective and stable electrocatalyst for efficient conversion of NO2- to NH3. Herein, a FeP nanoparticle-decorated TiO2 nanoribbon array on a titanium plate (FeP@TiO2/TP) is proposed as an efficient catalyst for NH3 production under ambient conditions. In 0.1 M NaOH with 0.1 M NO2-, such a FeP@TiO2/TP affords a large NH3 yield of 346.6 µmol h-1 cm-2 and a high Faradaic efficiency of 97.1%. Additionally, it demonstrates excellent stability and durability during long-term cycling tests and electrolysis experiments.

3D cauliflower-like Ni foam: a high-efficiency electrocatalyst for ammonia production via nitrite reduction.

A 3D cauliflower-like Ni foam on titanium plate (Ni foam/TP) shows high electrocatalytic performance for ambient ammonia (NH3) synthesis via nitrite (NO2-) reduction. In 0.1 M phosphate-buffered saline solution with 0.1 M NO2-, such Ni foam/TP attains a high NH3 Faradaic efficiency (FE) of 95.9% and a large NH3 yield of 742.7 µmol h-1 cm-2 at -0.8 V. Its Zn-NO2- battery offers a high power density of 6.2 mW cm-2 and an NH3 FE of 90.1%.

OSR1 downregulation indicates an unfavorable prognosis and activates the NF-κB pathway in ovarian cancer.

BACKGROUND: Odd-skipped related 1 (OSR1) has been reported as a tumor suppressor gene in various malignant tumors. The mechanism through which OSR1 regulates ovarian cancer (OC) progression remains unclear. MATERIALS AND METHODS: Immunohistochemistry was utilized to evaluate OSR1 expression in patients with ovarian cancer. We investigated the association between clinicopathological parameters and OSR1 expression in OC patients and the influence of OSR1 expression on patient survival and prognosis. OC cells with OSR1 overexpression or knockdown were established and validated using Western blot and Quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The influence of OSR1 on the NF-κB pathway was examined by analyzing the p-IκBα, IκBα, p65, and p-p65 protein expression. In vitro assays, such as cell cycle assay, Cell Counting Kit-8 (CCK-8), transwell invasion assay, wound healing migration assay, enzyme-linked immunoassay (ELISA), and Annexin V/PI flow cytometry apoptosis assay, were conducted to explore the effect of OSR1 knockdown or dual inhibition of OSR1 and the NF-κB pathway on OC malignant biological behavior. RESULTS: OSR1 expression was downregulated in OC tissues, with significant associations observed between its expression and The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue differentiation. Low OSR1 expression in OC patients correlated with reduced overall survival (OS) rates and poor prognosis. In vitro, experiments confirmed a negative correlation between OSR1 expression and NF-κB pathway activity. OSR1 knockdown facilitated OC cell malignant biological behavior, while the NF-κB pathway inhibitor (Bay 11-0782) reversed the impacts of OSR1 knockdown on cell proliferation, migration, invasion, and apoptosis. CONCLUSION: Our findings indicate that OSR1 is downregulated and associated with OC prognosis. OSR1 suppresses NF-κB pathway activity and inhibits OC progression by targeting the NF-κB pathway.

Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1α/RORγt pathway.

BACKGROUND: Acquired aplastic anemia (AA) is a life-threatening disease associated with an imbalance in Th17/Treg cells. Regulating this balance may be an effective treatment approach for AA. Rhodiola rosea has shown efficacy in AA treatment, but its mechanisms remain unclear. PURPOSE: We investigated salidroside's effect (a component of Rhodiola rosea) on Th17/Treg balance in adult AA patients and a mouse model. METHODS: HIF-1α mRNA and protein levels were measured in AA patients' peripheral blood. Flow cytometry, qRT-PCR, and WB analyzed salidroside's impact on T cell differentiation, Th17 cells, Treg cells, STAT3, HIF-1α, and RORγt expression. ELISA measured hematopoietic growth factors in mouse serum. RESULTS: AA patients exhibited elevated HIF-1α levels. Salidroside improved hematopoietic function, increasing blood cell count and enhancing bone marrow. Salidroside induced SCF, TPO, and IL-3 expression while inhibiting IL-2 in mice. Salidroside reduced STAT3, HIF-1α, RORγt, and IL-17a, while increasing FoxP3 expression, correcting the Th17/Treg imbalance in vitro and in vivo. CONCLUSION: Salidroside has potential as a novel AA treatment by correcting the Th17/Treg imbalance through the STAT3/HIF-1α/RORγt pathway.

HIV-1 molecular transmission network and drug resistance in Chongqing, China, among men who have sex with men (2018-2021).

BACKGROUND: Over the past few years, HIV transmission among men who have sex with men (MSM) in China has increased significantly. Chongqing, located in the southwest of China, has the highest prevalence of HIV among MSM in the country. METHODS: Blood samples were taken from 894 MSM in Chongqing who had recently been diagnosed with HIV-1 infection and had not yet started getting treatment. In order to determine the distribution of HIV-1 subtypes, transmitted drug resistance, and assessments of molecularly transmitted clusters, we sequenced the Pol genes and employed them in phylogenetic analysis. The genetic distance between molecular clusters was 1.5%. To find potential contributing factors, logistic regression analyses were performed. RESULTS: Of the 894 HIV-1 pol sequences acquired from study participants, we discovered that CRF07_BC (73.6%) and CRF01_AE (19.6%) were the two most prevalent HIV-1 genotypes in Chongqing among MSM, accounting for 93.2% of all infections. In addition, CRF08_BC (1.1%), B subtype (1.0%), CRF55_01B (3.4%), and URF/Other subtypes (1.3%) were less frequently observed. Among MSM in Chongqing, transmitted drug resistance (TDR) was reported to be present at a rate of 5.6%. 48 clusters with 600 (67.1%, 600/894) sequences were found by analysis of the molecular transmission network. The distributions of people by age, sexual orientation, syphilis, and genotype were significantly differentially related to being in clusters, according to the multivariable logistic regression model. CONCLUSION: Despite the low overall prevalence of TDR, the significance of genotypic drug resistance monitoring needs to be emphasized. CRF07_BC and CRF01_AE were the two main genotypes that created intricate molecular transmission networks. In order to prevent the expansion of molecular networks and stop the virus's spread among MSM in Chongqing, more effective HIV intervention plans should be introduced.

CXCL10 and CCL5 as feasible biomarkers for immunotherapy of homologous recombination deficient ovarian cancer.

This study aims to identify biomarkers of ovarian cancer, specifically those tumors exhibiting homologous recombination deficiency (HRD), to contribute to the optimization of immunotherapy. We screened the differentially expressed genes coding for CXCL10 and CCL5 by analyzing the transcriptome data of patient with different HRD scores in the ovarian cancer cohort of the TCGA database and validated our results using pathological tissue sections. The cellular origin of CXCL10 and CCL5 were identified using the single-cell sequencing data extracted from the GEO database combined with the tumor mutational burden (TMB) and single nucleotide polymorphism (SNP) data obtained from the TCGA database. We found that CXCL10 and CCL5 expression levels were correlated with HRD score. Analysis of single-cell sequencing results and tumor mutation data suggested that both CXCL10 and CCL5 present in the tumor microenvironment were primarily derived from immune cells. In addition, we found that samples with high expression of CXCL10 and CCL5 also had higher stromal cell and immune cell scores, indicating low tumor homogeny. Further analysis showed that CXCL10 and CCL5 expression was associated with immune checkpoint-related genes, and the efficacy of using these proteins as biomarkers was significantly higher than that of PD-1 in predicting the effect of anti-PD-1 immunotherapy. The expression of CXCL10 and CCL5 had statistically different effects on the survival of patients, based on multivariate Cox regression. In summary, the results demonstrate that in ovarian cancer, the expression of CXCL10 and CCL5 are correlated with HRD. When CXCL10 and CCL5 are secreted by immune cells, immune cell infiltration can be chemotactic and predict the effect of immunotherapy more efficiently than using PD-1 as a biomarker. Therefore, CXCL10 and CCL5 look to be promising novel biomarkers to guide immunotherapy in ovarian cancer.