A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

Telephone follow-up based on artificial intelligence technology among hypertension patients: Reliability study.

Artificial intelligence (AI) telephone is reliable for the follow-up and management of hypertensives. It takes less time and is equivalent to manual follow-up to a high degree. We conducted a reliability study to evaluate the efficiency of AI telephone follow-up in the management of hypertension. During May 18 and June 30, 2020, 350 hypertensives managed by the Pengpu Community Health Service Center in Shanghai were recruited for follow-up, once by AI and once by a human. The second follow-up was conducted within 3-7 days (mean 5.5 days). The mean length time of two calls were compared by paired t-test, and Cohen's Kappa coefficient was used to evaluate the reliability of the results between the two follow-up visits. The mean length time of AI calls was shorter (4.15 min) than that of manual calls (5.24 min, P < .001). The answers related to the symptoms showed moderate to substantial consistency (κ:.465-.624, P < .001), and those related to the complications showed fair consistency (κ:.349, P < .001). In terms of lifestyle, the answer related to smoking showed a very high consistency (κ:.915, P < .001), while those addressing salt consumption, alcohol consumption, and exercise showed moderate to substantial consistency (κ:.402-.645, P < .001). There was moderate consistency in regular usage of medication (κ:.484, P < .001).

[Fertility preservation through natural and artificial ovaries: a review].

Ovarian tissue cryopreservation (OTC) is currently the exclusive choice for preserving fertility in both young girls before reaching puberty and young women who require immediate chemotherapy. Ovarian tissue transplantation has proven to be effective in restoring hormonal cycles and fertility. However, in certain cancer cases, there is a potential risk of inadvertently reintroducing malignant cells when transplanting cryopreserved ovarian tissue. Therefore, the use of an artificial ovary as an innovative and complementary approach allows for the development of isolated follicles, facilitates oocyte maturation and ovulation, and can partially restore endocrine function. This paper presents a comprehensive overview of techniques used to preserve fertility in natural ovarian tissues, including slow freezing, vitrification and hydrogel encapsulation methods. Additionally, it reviews fertility preservation techniques for artificial ovarian tissues, such as strategies involving hydrogel-encapsulated follicle, scaffolding for constructing ovarian microtissues, and 3D printing engineering. Lastly, this article explores current challenges and difficulties encountered in preserving ovarian tissue fertility, while also anticipating future trends in development, making it a valuable reference for the implementation of ovarian tissue fertility preservation.

Role of miRNAs in macrophage-mediated kidney injury.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

Serum AXL is a potential molecular marker for predicting COVID-19 progression.

Background: The severity, symptoms, and outcome of COVID-19 is thought to be closely linked to how the virus enters host cells. This process involves the key roles of angiotensin-converting enzyme 2 (ACE2) and the Tyrosine protein kinase receptor UFO (AXL) receptors. However, there is limited research on the circulating levels of ACE2 and AXL and their implications in COVID-19. Methods: A control group of 71 uninfected individuals was also included in the study. According to the Guidance for Corona Virus Disease 2019 (10th edition), a cohort of 358 COVID-19 patients were categorized into non-severe and severe cases. Serum ACE2/AXL levels in COVID-19 patients were detected by enzyme-linked immunosorbent assay (ELISA) at different time points post-COVID-19 infection, including days 0-7, 8-15, 31-179 and >180 days. Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using an iFlash 3000 Chemiluminescence Immunoassay Analyzer. The receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the biological markers, and the association between laboratory parameters and illness progression were explored. Results: Compared with the uninfected group, the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased. AXL (AUC = 0.774) demonstrated a stronger predictive ability for COVID-19 than ACE2. In the first week after infection, only the level of AXL was statistically different between severe group and non-severe group. After first week, the levels of ACE2 and AXL were different in two groups. Moreover, in severe COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8-15 before declining, whereas serum SARS-COV-2 IgG levels continued to rise, reaching a peak at day 31-180 days before decreasing. In addition, the AXL level continued to decrease and the SARS-COV-2 IgG level continued to increase in the infected group after 180 days compared to the uninfected group. Conclusions: The levels of serum ACE2 and AXL correlate with COVID-19 severity. However, AXL can also provide early warning of clinical deterioration in the first week after infection. AXL appears to be a superior potential molecular marker for predicting COVID-19 progression.

Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

The role of dietary fats on cognition and sarcopenia in the elderly.

BACKGROUND AND OBJECTIVES: To elucidate the role of dietary fats on the relationship between mild cognitive impairment and sarcopenia and help identifying and preventing the decline of cognitive and muscle function in elderly individuals. METHODS AND STUDY DESIGN: The study conducted involving a group of 1812 individuals between the ages of 61 and 92. Body composition and BMR were assessed by bioelectrical impedance analysis. Cognitive function and dietary nutrition were evaluated by neuropsychological assessments and questionnaire of food intake frequency. Lipidomics analysis was performed using UHPLC-Qtrap-MS/MS. RESULTS: MCI and SA are mutual influencing factors, lower intake of MUFA, PUFA and higher intake of fat was associated with cognitive dysfunction and/or SA (p < 0.05). PUFA was important for MCI combined with SA (Compared with Q1, Q4 OR: 0.176, 95%CI: 0.058,0.533). Lipidomics analysis revealed that triacylglycerol (TAG) contain more carbon chains with saturated double bonds may be closely related to cognitive impairment and the progression of SA (p < 0.05). While, DAG with carbon chains of unsaturated double bonds is opposite. CONCLUSIONS: Insufficient intake of unsaturated fatty acids was associated with the development of cognitive decline and the progression of SA. MUFA affecting muscle health, fats and PUFA has a greater impact on MCI combined with SA. Less MUFA intake and increasing saturated double-bonded fatty acid intake might be the key factors on promoting cognitive impairment and SA in the elderly. They have the potential to serve as prospective biomarkers indicating a higher risk of cognitive decline and/or SA in the elderly population.

Potential Applications of Dual Haptoglobin Expression in the Reclassification and Treatment of Hepatocellular Carcinoma.

HCC is a malignancy characterized by high incidence and mortality rates. Traditional classifications of HCC primarily rely on tumor morphology, phenotype, and multicellular molecular levels, which may not accurately capture the cellular heterogeneity within the tumor. Current research on HCC using scRNA-seq is predominantly focused on immune and stromal cells. This study integrates scRNA-seq and bulk RNA-seq to spotlight HP as a critical gene. HP is highly expressed in HCC malignant cells and lowly expressed in T cells. Within malignant cells, elevated HP expression interacts with C3, promoting Th1-type responses via the C3/C3AR1 axis. In T cells, down-regulating HP expression favors the expression of Th1 cell-associated marker genes, potentially enhancing Th1-type responses. Consequently, we developed a "HP-promoted Th1 response reclassification" gene set, correlating higher activity scores with improved survival rates in HCC patients. Additionally, four predictive models for neoadjuvant treatment based on HP and C3 expression were established: 1) Low HP and C3 expression with high Th2 cell infiltration; 2) High HP and low C3 expression with high Th2 cell infiltration; 3) High HP and C3 expression with high Th1 cell infiltration; 4) Low HP and high C3 expression with high Th1 cell infiltration. In conclusion, the HP gene selected from the HCC malignant cell subgroup (Malignant_Sub 6) might serve as a potential ally against the tumor by promoting Th1-type immune responses. The establishment of the "HP-promoted Th1 response reclassification" gene set offers predictive insights for HCC patient survival prognosis and neoadjuvant treatment efficacy, providing directions for clinical treatments.

Genome-wide association analysis reveals potential genetic correlation and causality between circulating inflammatory proteins and amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease, continues to elude complete comprehension of its pathological underpinnings. Recent focus on inflammation in ALS pathogenesis prompts this investigation into the genetic correlation and potential causal relationships between circulating inflammatory proteins and ALS. METHODS: Genome-wide association study (GWAS) data encompassing 91 circulating inflammatory protein measures from 14,824 individuals of European ancestry, alongside records from 27,205 ALS cases and 110,881 controls, were employed. Assessment of genetic correlation and overlap utilized LD score regression (LDSC), high-definition likelihood (HDL), and genetic analysis integrating pleiotropy and annotation (GPA) methodologies. Identification of shared genetic loci involved pleiotropy analysis, functional mapping and annotation (FUMA), and co-localization analysis. Finally, Mendelian randomization was applied to probe causal relationships between inflammatory proteins and ALS. RESULTS: Our investigation revealed significant genetic correlation and overlap between ALS and various inflammatory proteins, including C-C motif chemokine 28, Interleukin-18, C-X-C motif chemokine 1, and Leukemia inhibitory factor receptor (LIFR). Pleiotropy analysis uncovered shared variations at specific genetic loci, some of which bore potential harm. Mendelian randomization analysis suggested that alterations in specific inflammatory protein levels, notably LIFR, could impact ALS risk. CONCLUSIONS: Our findings uncover a genetic correlation between certain circulating inflammatory proteins and ALS, suggesting their possible causal involvement in ALS pathogenesis. Moreover, the identification of LIFR as a crucial protein may yield new insights into ALS pathomechanisms and offer a promising avenue for therapeutic interventions. These discoveries provide novel perspectives for advancing the comprehension of ALS pathophysiology and exploring potential therapeutic avenues.

Gender and race disparities in the prevalence of chronic kidney disease among individuals with hypertension in the United States, 2001-2016.

Background: Chronic kidney disease (CKD) is a common complication among individuals with hypertension. We aimed to identify the prevalence of CKD and the sex and race disparities within the hypertensive population in the United States from 2001-2016. Methods: A total of 16,148 participants with hypertension were included, representing 561,909,480 individuals from the U.S. population between 2001 and 2016, as documented in the National Health and Nutrition Examination Survey. The prevalence of albuminuria and CKD stage were assessed using survey-weighted general linear regression analysis. Heterogeneity in the CKD stage among the hypertensive population, stratified by sex and race, was identified through survey-weighted logistic regression analysis. Results: Overall, the prevalence of albuminuria remained stable (p for trend = 0.3196), and changes in the CKD stage were minimal (p for trend > 0.05) from 2001-2016. In the analysis of CKD stage heterogeneity by sex and race, the prevalence of CKD was higher among women than men and higher among individuals of other races combined than non-Hispanic Whites, but the differences were not statistically significant. Conclusion: The overall CKD stage within the hypertensive population plateaued between 2001 and 2016. Our findings highlight the importance of continuous monitoring and potential refinement of renoprotection strategies in individuals with hypertension to mitigate the persistent burden of CKD and address health disparities among different demographic groups.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis.

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood pathophysiology. Recent studies have highlighted systemic inflammation, especially the role of circulating inflammatory proteins, in ALS. Methods: This study investigates the potential causal link between these proteins and ALS. We employed a two-sample Mendelian Randomization(MR) approach, analyzing data from large-scale genome-wide association studies to explore the relationship between 91 circulating inflammatory proteins and ALS. This included various MR methods like MR Egger, weighted median, and inverse-variance weighted, complemented by sensitivity analyses for robust results. Results: Significant associations were observed between levels of inflammatory proteins, including Adenosine Deaminase, Interleukin-17C, Oncostatin-M, Leukemia Inhibitory Factor Receptor, and Osteoprotegerin, and ALS risk. Consistencies were noted across different P-value thresholds. Bidirectional MR suggested that ALS risk might influence levels of certain inflammatory proteins. Discussion: Our findings, via MR analysis, indicate a potential causal relationship between circulating inflammatory proteins and ALS. This sheds new light on ALS pathophysiology and suggests possible therapeutic targets. Further research is required to confirm these results and understand the specific roles of these proteins in ALS.

CENPK orchestrates ovarian cancer progression via GOLPH3-Mediated activation of mTOR signaling.

Ovarian cancer stands as a formidable clinical challenge, with limited therapeutic options. This investigation delves into the intricate molecular mechanisms governing ovarian cancer progression and uncovers Centromere Protein K (CENPK) as a central figure in disease pathogenesis. Elevated CENPK levels within ovarian cancer tissues conspicuously align with adverse clinical outcomes, positioning CENPK as a promising prognostic biomarker. Deeper exploration reveals a direct transcriptional connection between CENPK and the E2F1 transcription factor and clearly establishes E2F1's role as the master regulator of CENPK expression in ovarian cancer. Our inquiry revealing a suppression of tumor-promoting signaling pathways, most notably the mTOR pathway, upon CENPK silencing. Intriguingly, CENPK renders ovarian cancer cells more responsive to the mTOR inhibitor rapamycin, introducing a promising avenue for therapeutic intervention. In summation, our study unravels the multifaceted role of CENPK in ovarian cancer progression. It emerges as a prognostic indicator, a pivotal mediator of cell proliferation and tumorigenicity, and a regulator of the mTOR pathway, shedding light on potential therapeutic avenues for this formidable disease.

Exploration of radiotherapy strategy for brain metastasis patients with driver gene positivity in lung cancer.

Objective: To assess the disparities in effectiveness and identify outcome predictors in the treatment of a targeted-first and radiotherapy-first regimen with driver gene-positive lung cancer brain metastases. Materials and Methods: This retrospective study analyzed patients with driver gene-positive lung cancer brain metastases who received first-targeted and first-radiotherapy regimens, respectively, with SIB-WBRT (whole brain tissue 40 Gy/20 fractions, tumor tissue boosted to 56-60 Gy/20 fractions) and local irradiation (prescription dose range of 20-60 Gy/2-25 fractions, most commonly delivered as 30 Gy/5 fractions, with a BED range of 28-100.8 Gy) at Peking Union Medical College Hospital from September 2015 to December 2021. The primary endpoint was intracranial progression free survival (iPFS). Secondary endpoints included overall survival (OS), intracranial new lesions, and tumor control. The Kaplan-Meier method was utilized to depict and estimate iPFS, OS, intracranial new lesions and tumor control. The Cox regression analysis was conducted to assess the association between relevant factors and outcomes. Results: 88 patients were enrolled in targeted-first and radiotherapy-first regimen, totally. And no difference was found in the comparison of iPFS between the two groups (HR=1.180, 95%CI: 0.622-2.237, P=0.613). No difference was found in the comparison of OS between the two groups (HR=1.208, 95%CI: 0.679-2.150, P=0.520). No difference was found in the comparison of intracranial new lesions between the two groups (HR=1.184, 95%CI: 0.569-2.463, P=0.652). There was a difference in the local control time between the two groups, with radiotherapy-first regimen being superior (HR=2.397, 95% CI:1.453-3.954, P<0.001). Patient age (HR=1.054, 95%CI: 1.026- 1.082, P<0.001), radiotherapy modality (HR=0.128, 95%CI: 0.041-0.401, P<0.001), metastasis volume (HR=1.426, 95%CI: 1.209-1.682, P<0.001), number of metastases(HR=14.960, 95%CI: 1.990-112.444, P=0.009), extracranial disease status (HR=0.387, 95%CI: 0.170-0.880, P=0.023) and therapy sequence (HR=13.800, 95%CI: 4.455-42.751, P<0.001) were associated with local control. Conclusion: Targeted-first regimen was not found to improve patients' iPFS relative to radiotherapy-first regimen in patients with brain metastases. Radiotherapy-first regimen for brain metastases demonstrated superior local control compared to targeted-first regimen. Patient's age, radiotherapy modality, metastasis volume, number of metastases, extracranial disease status and therapy sequence may be related to local control of metastases.

Spontaneous rupture of bladder diverticulum with pseudo renal failure:A case report and literature review.

BACKGROUND: Spontaneous or non-traumatic bladder rupture is rare but can be life-threatening. Bladder rupture caused by a diverticulum is extremely rare, with only a few case reports in medical literature. CASE PRESENTATION: We report the case of a 32-year-old woman admitted to hospital complaints of abdominal pain, oliguria and ascites with no history of trauma. Laboratory tests revealed an elevated serum urea nitrogen(UN) level of 33.5 mmol/l and an elevated creatinine levels of 528 umol/l. X-ray cystography confirmed the rupture of a bladder diverticulum. Subsequent transurethral catheterization led to a prompt increase in urinary output, and serum creatinine level returned to 40 umol/l within 48 h. The patient was successfully treated with laparoscopic diverticulectomy. CONCLUSION: Clinicians should maintain a high level of suspicion for urinary bladder rupture in cases presenting with acute lower abdominal pain, urinary difficulties, and oliguria. When acute renal failure, complicated ascites, and an elevated peritoneal fluid creatinine or potassium level exceeding serum levels are observed, intraperitoneal urine leakage should be suspected without delay. This case emphasizes the importance of early diagnosis and intervention in managing this rare but serious condition.

HPV-associated cervicovaginal microbiome and host metabolome characteristics.

BACKGROUND: Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. RESULTS: The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. CONCLUSION: The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism.

OBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear. METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated. RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment. CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.

Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.

The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.