Recombinant human thrombopoietin therapy for primary immune thrombocytopenia in pregnancy: a retrospective comparative cohort study.

BACKGROUND: Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. AIMS: To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. METHODS: From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 109/L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment. RESULTS: The baseline characteristics were comparable between both groups (P > 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5-67.5] vs. 25 [19-29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P < 0.001). Gestational weeks of delivery (37.6 [37-38.4] vs 37.1 [37-37.2] weeks, P = 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all P > 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. CONCLUSION: rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.

Role and mechanism of the p-JAK2/p-STAT3 signaling pathway in follicular development in PCOS rats.

OBJECTIVE: To identify the association between the phosphorylated Janus kinase 2/phosphorylated signal transducer and activator of transcription (p-JAK2/p-STAT3) signaling pathway and follicular development in polycystic ovary syndrome (PCOS) rats, and explore the underlying mechanism. To evaluate the role of exogenous JAK2 inhibitor AG490 in the model and the associations among luteinizing hormone/choriogonadotropin receptor (LHCGR), follicle-stimulating hormone receptor (FSHR), cytochrome P450 17α (CYP17a), cytochrome P450 19 (CYP19), and PCOS. RESULTS: Rat models of PCOS was established. PCOS rats were intraperitoneally treated with double-distilled water (ddH2O)/DMSO/AG490. The rate of ovarian morphological recovery in the AG490 group was significantly higher compared with the DMSO group (83.3 % vs 9.1 %, X2 = 12.68, P < 0.001). Moreover, the short in the time the estrous cycle was resumed in the AG490 group (hazard ratio = 16.32, P < 0.001) compared with the DMSO group. Compared with the controls, p-JAK2, p-STAT3, LHCGR, and CYP17a expression levels were increased whereas that of FSHR and CYP19 were decreased in the ovaries of PCOS rats. However, an opposite trend was observed after treatment with AG490. Software prediction revealed that the p-STAT3 bound to the promoter regions of LHCGR, FSHR, CYP17a, and CYP19 genes. This finding was confirmed by results of correlation analysis (R = 0.834, -0.836, 0.875 and -0.712, respectively, all P < 0.001). CONCLUSION: This study demonstrated that the p-JAK2/p-STAT3 signaling pathway was involved in follicular development in PCOS rats by upregulating LHCGR and CYP17a expression, and downregulating that of FSHR and CYP19. AG490 treatment exerted beneficial effects. LHCGR, FSHR, CYP17a, and CYP19 are candidate genes associated with follicular development in PCOS rats.

Clinical nutrition service capacity of 445 secondary or above hospitals in Sichuan, China: the 2021 annual survey.

BACKGROUND AND OBJECTIVES: To investigate the capacity of clinical nutrition services in secondary and tertiary hospitals in the Sichuan Province, China. METHODS AND STUDY DESIGN: Convenience sampling was used. E-questionnaires were distributed to all eligible medical institutions in Sichuan through the official network of provincial and municipal clinical nutrition quality control centers. The data obtained were sorted in Microsoft Excel and analyzed by SPSS. RESULTS: A total of 519 questionnaires were returned, of which 455 were valid. Only 228 hospitals were accessible to clinical nutrition services, of which 127 hospitals had independently set up clinical nutrition departments (CNDs). The ratio of clinical nutritionists to beds was 1:214. During the last decade, the rate of constructing new CNDs was maintained at approximately 5 units/year. A total of 72.4% of hospitals managed their clinical nutrition units as part of their medical technology departments. The specialist number ratio of senior, associate, intermediate and junior is approximately 1:4:8:10. There were 5 common charges for clinical nutrition. CONCLUSIONS: The sample representation was limited, and the capacity of clinical nutrition services may have been overestimated. Secondary and tertiary hospitals in Sichuan are currently in the second high tide of department establishment, with a positive trend of departmental affiliation standardization and a basic formation of a talent echelon.

MicroRNA-423-5p Mediates Cocaine-Induced Smooth Muscle Cell Contraction by Targeting Cacna2d2.

Cocaine abuse increases the risk of atherosclerotic cardiovascular disease (CVD) and causes acute coronary syndromes (ACS) and hypertension (HTN). Significant research has explored the role of the sympathetic nervous system mediating the cocaine effects on the cardiovascular (CV) system. However, the response of the sympathetic nervous system alone is insufficient to completely account for the CV consequences seen in cocaine users. In this study, we examined the role of microRNAs (miRNAs) in mediating the effect of cocaine on the CV system. MiRNAs regulate many important biological processes and have been associated with both response to cocaine and CV disease development. Multiple miRNAs have altered expression in the CV system (CVS) upon cocaine exposure. To understand the molecular mechanisms underlying the cocaine response in the CV system, we studied the role of miRNA-423-5p and its target Cacna2d2 in the regulation of intracellular calcium concentration and SMC contractility, a critical factor in the modulation of blood pressure (BP). We used in vivo models to evaluate BP and aortic stiffness. In vitro, cocaine treatment decreased miR-423-5p expression and increased Cacna2d2 expression, which led to elevated intracellular calcium concentrations and increased SMC contractility. Overexpression of miR-423-5p, silencing of its target Cacna2d2, and treatment with a calcium channel blocker reversed the elevated SMC contractility caused by cocaine. In contrast, suppression of miR-423-5p increased the intracellular calcium concentration and SMC contractibility. In vivo, smooth muscle-specific overexpression of miR-423-5p ameliorated the increase in BP and aortic stiffness associated with cocaine use. Thus, miR-423-5p regulates SMC contraction by modulating Cacna2d2 expression increasing intracellular calcium concentrations. Modulation of the miR-423-5p-Cacna2d2-Calcium transport pathway may represent a novel therapeutic strategy to improve cocaine-induced HTN and aortic stiffness.

Relevance of small right-to-left shunt in contrast-enhanced transcranial Doppler in young and middle-aged patients with cryptogenic stroke: a report of two cases and literature review.

AIM: The clinical relevance of small right-to-left shunt (RLS) in young patients with cryptogenic stroke is unknown. We aimed to analyze and understand the relationship between cryptogenic stroke and small RLS by studying specific cases. MATERIALS AND METHODS: Clinical data from two cases of small RLS-related cryptogenic stroke in young patients were collected prospectively and analyzed. We followed up the patients for >1 year after discharge. RESULTS: Case 1. A 50-year-old man was admitted for slurred speech and right hemiplegia and was diagnosed with acute cerebral infarction. Contrast-enhanced transcranial Doppler (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) revealed a microbubble and 20-30 microbubbles per section, respectively, in the resting state. Three months later, he was readmitted for stroke recurrence. Transesophageal echocardiography (TEE) confirmed a patent foramen ovale (PFO), and he underwent transcatheter closure of the PFO. Case 2. A 48-year-old man was admitted for right hemiplegia with slurred speech. Brain magnetic resonance imaging showed acute cerebral infarction. c-TCD and contrast-enhanced TEE (c-TEE) revealed <10 microbubbles and approximately 20 microbubbles per section, respectively. These findings suggested a PFO. Two months later, he was readmitted for stroke recurrence. He underwent transcatheter closure of the PFO. Follow-up of cases 1 and 2 at >1 and >1.5 years after discharge, respectively, showed no stroke recurrence. CONCLUSION: We suspected that a small RLS may cause cryptogenic stroke. A small RLS in c-TCD in stroke patients may not be actually small, and c-TEE/c-TTE may be valuable in finding larger RLSs.

Disruption of Aokap6 near the kojic acid gene cluster affects the growth and kojic acid production in Aspergillus oryzae.

The kojic acid gene cluster of Aspergillus oryzae plays a key role in kojic acid synthesis. Although the kojic acid gene cluster has been found in 2010, there is little information on the function of the genes located near the kojic acid gene cluster of A. oryzae and whether these genes affect the kojic acid gene cluster containing kojA, kojR and kojT. Here, Aokap6 near the kojic acid gene cluster of A. oryzae was identified and characterized. The Aokap6 disrupted mutants were constructed by the CRISPR/Cas9 system, which exhibited increased mycelium growth and conidial formation. Disruption of Aokap6 enhanced the tolerance to cell wall, oxidative and heat stress but not osmotic stress. Deletion of Aokap6 repressed kojic acid production, together with the reduced expression of kojA, kojR and kojT. Meanwhile, knockout of kojA, kojR and kojT led to the declined expression of Aokap6, indicating that Aokap6 is required for kojic acid production in coordination with kojA, kojR and kojT. Furthermore, overexpression of kojA, kojR and kojT had no effects on the transcript level of Aokap6, and overexpression of kojA in Aokap6 deletion strain could rescue the reduced yield of kojic acid, suggesting that Aokap6 is involved in kojic acid synthesis acting upstream of kojA. These findings provide new insight for the further understanding of kojic acid gene cluster and kojic acid production in A. oryzae.

Analysis of Macular Microperimetry Characteristics in Non-Arteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND The aim of this study was to analyze the correlation of macular micro-field characteristics with vision and visual field in patients with non-arteritic anterior ischemic optic neuropathy. MATERIAL AND METHODS Retrospective case analysis was performed. Fifty-eight NAION patients with 62 affected eyes were included in the study. In addition, 54 eyes not affected by NAION from 54 patients among the 58 patients were included as controls. All eyes underwent best corrected visual acuity (BCVA) test, slit lamp biomicroscopy, indirect ophthalmoscopy, visual field examination, and microperimetry. BCVA was converted into logarithm of minimum angle of resolution (LogMAR) for statistical analysis. There was no significant difference in age, sex, eye type, or intraocular pressure between the 2 groups. The macular integrity assessment (MAIA) instrument was used for microperimetry. Mean light sensitivity (microMS) in the 10° macular region and the fixation rates for macular fovea 2° and 4° were recorded. Spearman correlation analysis was performed. RESULTS The microMS values were significantly different between the control group and the affected eye group (t=-2.427, P=0.036). MicroMS was significantly correlated with logMAR BCVA (r=-0.802, P=-0.005) and with mean sensitivity (MS) and mean deviation (MD) (r=0.912, P=0.002; r=-0.905, P=0.002; P<0.05). MS and MD were not correlated with logMAR BCVA (r=-0.465, P=0.245; r=0.437, P=0.278). CONCLUSIONS The present study demonstrates that microMS of macular micro-visual field in NAION patients was significantly decreased at early stage, and was significantly correlated with and consistent with visual acuity and visual field.

MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression.

OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair. The aim of this study was to characterize the role of the miR-146a-Polo-like kinase 2 (Plk2) network in regulating lin- BMC senescence, apoptosis, and their angiogenic capability. APPROACH AND RESULTS: Transcriptome analysis in lin- BMCs isolated from young and aged wild-type and ApoE-/- (apolipoprotein E) mice showed a significant age-associated increase in miR-146a expression. In silico analysis, expression study and Luciferase reporter assay established Plk2 as a direct target of miR-146a. miR-146a overexpression in young lin- BMCs inhibited Plk2 expression, resulting in increased senescence and apoptosis, via p16Ink4a/p19Arf and p53, respectively, as well as impaired angiogenic capacity in vitro and in vivo. Conversely, suppression of miR-146a in aged lin- BMCs increased Plk2 expression and rejuvenated lin- BMCs, resulting in decreased senescence and apoptosis, leading to improved angiogenesis. CONCLUSIONS: (1) miR-146a regulates lin- BMC senescence and apoptosis by suppressing Plk2 expression that, in turn, activates p16Ink4a/p19Arf and p53 and (2) modulation of miR-146a or its target Plk2 may represent a potential therapeutic intervention to improve lin- BMC-mediated angiogenesis and vascular repair.

Occult invasive cervical cancer after simple hysterectomy: a multi-center retrospective study of 89 cases.

BACKGROUND: Occult invasive cervical cancer (OICC) is sometimes incidentally found in surgical specimens after a simple hysterectomy (SH). This study was aimed at identifying a subset of patients with OICC who have a favorable prognosis. This patient group may not require adjuvant radiotherapy and other procedures. METHODS: The medical records of women in whom OICC was detected after an inadvertent SH were retrospectively reviewed. The relevant data, including clinicopathological characteristics, treatment and clinical outcome were evaluated. The primary and secondary endpoints were overall survival (OS) and relapse-free survival (RFS), respectively. RESULTS: Eighty-nine patients who met the inclusion criteria were included for analysis, and the risk of OICC was found to be 1.9 %. Finding an invasive cancer in a hysterectomy specimen after a conization procedure that shows positive margins was the most common reason (41.6 %) for the performance of inadvertent SH. In the univariate analysis, a tumor width > 20 mm, deep stromal invasion, and lymph node metastasis (LNM) were adversely associated with relapse (P < 0.001, < 0.001, and = 0.001, respectively) and survival (P = 0.003, 0.004, and 0.027, respectively), although these parameters were not independently associated with patient prognoses in the multivariate analysis. In patients with a tumor width ≤ 20 mm and superficial stromal invasion in the observation subgroup, the 5-year RFS and 5-year OS were both 100 %, whereas they were 57.1 % and 66.7 %, respectively, in patients with a tumor size > 20 mm and deep stromal invasion in the radiotherapy or chemotherapy subgroup (P < 0.001, and = 0.008, respectively). CONCLUSIONS: Simple observation after a lymphadenectomy procedure may be feasible in OICC patients with a tumor width ≤ 20 mm, superficial stromal invasion, a negative section margin in hysterectomy specimens, and no LNM.

Fibroblast growth factor receptor 4 (FGFR4) deficiency improves insulin resistance and glucose metabolism under diet-induced obesity conditions.

The role of fibroblast growth factor receptor 4 (FGFR4) in regulating bile acid synthesis has been well defined; however, its reported role on glucose and energy metabolism remains unresolved. Here, we show that FGFR4 deficiency in mice leads to improvement in glucose metabolism, insulin sensitivity, and reduction in body weight under high fat conditions. Mechanism of action studies in FGFR4-deficient mice suggest that the effects are mediated in part by increased plasma levels of adiponectin and the endocrine FGF factors FGF21 and FGF15, the latter of which increase in response to an elevated bile acid pool. Direct actions of increased bile acids on bile acid receptors, and other potential indirect mechanisms, may also contribute to the observed metabolic changes. The results described herein suggest that FGFR4 antagonists alone, or in combination with other agents, could serve as a novel treatment for diabetes.

A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries.

STUDY OBJECTIVE: To evaluate the safety and efficacy of a new crosslinked hyaluronan (NCH) gel in reducing postoperative adhesions. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTINGS: Seven departments of obstetrics and gynecology in China. PATIENTS: A total of 216 women scheduled for gynecologic laparoscopic surgery for primary removal of adhesions, myomas, ovarian cysts, or endometriotic cysts. INTERVENTIONS: Patients were randomized to receive either NCH gel or saline with 1:1 allocation. MEASUREMENTS AND MAIN RESULTS: All patients were evaluated using a modified American Fertility Society (mAFS) scoring system for the incidence, extent, and severity of pre-existing and postoperative adhesions at the 10 anatomic sites of ovaries/tubes and at the expanded 23 or 24 anatomic sites throughout the abdominopelvic cavity by laparoscopy. A total of 215 randomized patients were treated with either saline solution (108 of 108) or NCH gel (107 of 108), composing the full analysis set (FAS), and 196 patients (94 of 108 in the saline control group and 102 of 108 in the NCH gel group) completed the entire study, composing the per protocol set (PPS). The postoperative incidence of moderate or severe adhesions evaluated at the 10 sites (the primary endpoint for efficacy) was 27.7% in the control group and 9.8% in the NCH gel group, a difference of 14.4% (95% confidence interval [CI], 2.6%-20.6%) in the PPS, and 37.0% in the control group and 14.0% in the NCH gel group, a difference of 20.0% (95% CI, 8.9%-26.8%) in the FAS. The postoperative incidence of moderate or severe adhesions evaluated at the 24 sites was also significantly lower in the NCH gel group compared with the control group (5.9% vs 14.9%; p = .036) in the PPS. Also in the PPS, the NCH gel group had significantly lower postoperative adhesion scores of severity, extent, and mAFS: 60.0%, 50.8%, and 76.9%, respectively (median scores of the 10 sites; p = .002) and 48.5%, 50.0%, and 72.2% (median scores of the 24 sites; p = .001) lower than those recorded in the control group. No serious adverse events were observed, and the safety profile of NCH gel was comparable to that of saline control. CONCLUSION: This study demonstrates that NCH gel is safe and significantly reduces adnexal adhesion formation and global adhesion formation throughout the abdominopelvic cavity after gynecologic laparoscopic surgery.

[Sucrose gel for treatment of bacterial vaginosis: a randomized, double-blind, multi-center, parallel-group, phase III clinical trial].

OBJECTIVE: To evaluate the cure effectiveness and safety of sucrose gel in the treatment of bacterial vaginosis through a multi-center, randomized, double-blind, parallel controlled clinical study. METHODS: A clinical research method of multi-center, randomly double-blind, and dose group parallel comparison was adopted. In the study, 533 patients with bacterial vaginosis were randomly divided into two groups, which included 214 cases in the control group (5.0 g metronidazole gel) and 319 cases in the trial group (5.0 g sucrose gel ). The patients were treated with different medication according to the group where they were. All the cases in these two groups were treated with drugs vaginally twice in a day, morning and evening separately, for 5 days. The curative effect and safety evaluation were assessed from 7 to 10 days and 21 to 30 days after treatment respectively. RESULTS: The efficacy of the comprehensive clinical treatment showed that the cure rate of metronidazole gel group and sucrose gel group were 70.53% and 80.83% respectively 7 to 10 days after treatment. The recovery rate of Nugent score for vaginal smear were 71.50% and 81.15% respectively. The differences in the efficacy between these two groups were significant statistically (P<0.05). However, the cure rates of metronidazole gel group and sucrose gel group were 63.29% and 61.98% respectively 21 to 30 days after treatment. No statistically significant difference (P>0.05) could be found in the cure rates of the two groups. CONCLUSION: The clinical comprehensive efficacy and recovery of vaginal bacteria of sucrose gel group in the treatment of bacterial vaginosis were obviously superior to those of metronidazole gel 7 to 10 days after treatment. The susucrose gel could improve the clinical efficacy index and laboratory index of bacterial vaginosis. Other effects included the release of clinical symptoms, and the recovery of the normal micro-environment in the vagina according to the Nugent score. The curative efficacy of sucrose gel was equal to that of metronidazole gel 21 to 30 days after treatment. In the future, sucrose gel treatment can be a new strategy for the treatment of bacterial vaginosis. Various advantages can be taken to improve the cure rate of bacterial vaginosis and reduce the shortcomings produced by this disease.

Synergistic induction of miR-126 by hypoxia and HDAC inhibitors in cardiac myocytes.

HDAC inhibitors are under clinical development for the treatment of hypertrophic cardiomyopathy and heart failure although the mechanisms of protection are incompletely understood. Micro-RNA 126, an endothelium-specific miR has been assigned essential developmental roles in the heart by activating survival kinases ERK1/2 and Akt and increasing pro-angiogenic signaling. Here we provide the first evidence that hypoxia and HDAC inhibitors selectively and synergistically stimulate expression of miR-126 in cardiac myocytes. MiR-126 expression was increased 1.7-fold (p<0.05) after 1h of hypoxic exposure and this was further enhanced to 3.0-fold (p<0.01) by simultaneously blocking HDAC with the pan-HDAC inhibitor Tricostatin A (TSA). TSA alone did not increase miR-126. In parallel, hypoxia and TSA synergistically increased p-ERK and p-Akt without effecting VEGF-A level. Knockdown of miR-126 with si-RNA eliminated inductions of p-ERK and p-Akt by hypoxia, whereas miR-126 overexpression mimicked hypoxia and amplified p-ERK and p-Akt in parallel with miR-126. The results suggest that miR-126 is a hypoxia-inducible target of HAT/HDAC and its activation in cardiac myocytes may contribute to cardioprotection by activating cell survival and pro-angiogenic pathways selectively during ischemia.

[Survey on characteristics of menopause of Chinese women with the age of 40-60 years at gynecological clinic from 14 hospitals].

OBJECTIVE: To investigate the characteristics of menopause of Chinese women with the age of 40-60 years concerning gynecologic clinics in China. METHODS: From Mar.2008 to Sept.2008, a face-to-face questionnaire was conducted in gynecological clinic in perimenopausal and postmenopausal women in 14 hospitals in China, which included general demographic data, menstrual change process, climacteric symptoms and knowledge about menopause. Modified Kupperman index were used to evaluate climacteric symptoms during the recent week and awareness of hormonal replacement therapy were studied. RESULTS: A total of 1641 women were investigated. The ages of onset of menopause transition, climacteric symptoms and natural menopause were (47 ± 4), (46 ± 4), (49 ± 3) years old respectively. Climacteric symptoms could be found in 78.43% (1287/1641) women during menopausal transition, which were mainly mild to moderate symptoms. The top 5 symptoms were fatigue and weakness (71.48%, 1173/1641), irritability (68.68%, 1127/1641), insomnia (67.65%, 1110/1641), muscle and joint pain (64.11%, 1052/1641) and hot flush (57.90%, 950/1641). The climacteric symptoms were not constant during menopausal transition, usually more severe in late transition and postmenopausal periods, during which the moderate and severe symptoms were 59.1% (189/320) and 51.1% (291/570) respectively. Although most symptoms primarily appeared along with menstruation change, there are about 17.5% (172/981) patients experienced climacteric symptoms before menstruation change occurrence. There were 56.39% (733/1300) women had ever heard (mostly from gynecologist) about hormone replacement therapy from Obstetrician and Gynecologist. CONCLUSIONS: Most of the women during menopausal transition had climacteric symptoms, usually mild and moderate ones. Although most symptoms primarily appeared along with menstruation change, there are other patients' experienced climacteric symptoms before menstruation change occurrence.

Tumor-associated myeloid cells in cancer immunotherapy.

Tumor-associated myeloid cells (TAMCs) are among the most important immune cell populations in the tumor microenvironment, and play a significant role on the efficacy of immune checkpoint blockade. Understanding the origin of TAMCs was found to be the essential to determining their functional heterogeneity and, developing cancer immunotherapy strategies. While myeloid-biased differentiation in the bone marrow has been traditionally considered as the primary source of TAMCs, the abnormal differentiation of splenic hematopoietic stem and progenitor cells, erythroid progenitor cells, and B precursor cells in the spleen, as well as embryo-derived TAMCs, have been depicted as important origins of TAMCs. This review article provides an overview of the literature with a focus on the recent research progress evaluating the heterogeneity of TAMCs origins. Moreover, this review summarizes the major therapeutic strategies targeting TAMCs with heterogeneous sources, shedding light on their implications for cancer antitumor immunotherapies.

Prevalence of and risk factors for chlamydia in female outpatients with genital tract infections: a nationwide multi-center, cross-sectional study in China.

Introduction: Chlamydia trachomatis is the etiological agent of the commonest sexually transmitted bacterial infection. This study aimed to examine the prevalence of genital chlamydia and associated risk factors in Chinese female outpatients with genital tract infections. Methods: A prospective, multicenter epidemiological study of genital chlamydia prevalence in 3008 patients with genital tract infections in 13 hospitals in 12 provinces of China was performed between May 2017 and November 2018. Vaginal secretion specimens were collected for the clinical diagnosis of vaginitis, whereas cervical secretion specimens were tested for Chlamydia trachomatis and Neisseria gonorrhoeae. All patients participated in a one-on-one cross-sectional questionnaire interview. Results: Totally 2,908 participants were included. The prevalence rates of chlamydia and gonococcal infections in women with genital tract infections were 6.33% (184/2908) and 0.01% (20/2908), respectively. Multivariate analysis showed high risk factors for chlamydia were premarital sex behavior, first sexual intercourse before the age of 20 and bacterial vaginosis. Discussion: Given that most chlamydia cases are asymptomatic and no vaccine is currently available, chlamydia prevention strategies should include behavioral interventions as well as early screening programs to identify and treat individuals with genital tract infections, especially those with the above identified risk factors.

c-Jun N-terminal kinase (JNK-1) confers protection against brief but not extended ischemia during acute myocardial infarction.

Brief periods of ischemia do not damage the heart and can actually protect against reperfusion injury caused by extended ischemia. It is not known what causes the transition from protection to irreversible damage as ischemia progresses. c-Jun N-terminal kinase-1 (JNK-1) is a stress-regulated kinase that is activated by reactive oxygen and thought to promote injury during severe acute myocardial infarction. Because some reports suggest that JNK-1 can also be protective, we hypothesized that the function of JNK-1 depends on the metabolic state of the heart at the time of reperfusion, a condition that changes progressively with duration of ischemia. Mice treated with JNK-1 inhibitors or transgenic mice wherein the JNK-1 gene was ablated were subjected to 5 or 20 min of ischemia followed by reperfusion. When JNK-1 was inactive, ischemia of only 5 min duration caused massive apoptosis, infarction, and negative remodeling that was equivalent to or greater than extended ischemia. Conversely, when ischemia was extended JNK-1 inactivation was protective. Mechanisms of the JNK-1 switch in function were investigated in vivo and in cultured cardiac myocytes. In vitro there was a comparable switch in the function of JNK-1 from protective when ATP levels were maintained during hypoxia to injurious when reoxygenation followed glucose and ATP depletion. Both apoptotic and necrotic death pathways were affected and responded reciprocally to JNK-1 inhibitors. JNK-1 differentially regulated Akt phosphorylation of the regulatory sites Ser-473 and Thr-450 and the catalytic Thr-308 site in vivo. The studies define a novel role for JNK-1 as a conditional survival kinase that protects the heart against brief but not protracted ischemia.

[Effects of PI3K/Akt/NF-κB signal pathway on FSH facilitation on cell proliferation and invasion by human epithelial ovarian cancer].

OBJECTIVE: To explore the effects of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signal pathway on the process of follicle-stimulating hormone (FSH) facilitating cell proliferation and invasion in human epithelial ovarian cancer. METHODS: Ovarian cancer cell lines SKOV3 and 3AO were cultured to exponential phase, then assigned to control group, FSH group, LY294002 group and FSH + LY294002 group, respectively. Cells were treated with different concentration of FSH and LY294002, respectively. The effects of FSH on cell proliferation were observed by methylthiazolyl tetrazolium (MTT). Morphological changes were observed by phase contrast microscope. The ability of cell invasion was investigated by transwell invasion assay. The expression of FSH receptor (FSHR), Akt1/2, phosphorylated-Akt (p-Akt) and NF-κB p65 protein were detected by western blot. RESULTS: (1) FSH could promote the proliferation of SKOV3 and 3AO cells. When the cells were treated with 40 U/L FSH for 48 hours (SKOV3) and 24 hours (3AO), compared with those in control groups, they reached the highest proliferation rate (P < 0.05), respectively. (2) The morphology of SKOV3 and 3AO cells in four groups:in control group, SKOV3 cells were short spindle and 3AO cells were long spindle, the nuclei of them were both roundness or oval, the cytoplasm were bright. In FSH group, the cells changed to slightly longer or polygonal, they were full in shape, meanwhile, the cell intensity were higher than control group. In LY294002 group, some cells changed from spindle to round, and began to shrink. The cell intensity diminished. The morphology of FSH + LY294002 group was similar with control group, but the cell intensity was lower than that in FSH group. (3) The number of SKOV3 cell that passed through the membrane in control group, FSH group, LY294002 group and FSH + LY294002 group was (26 ± 6), (118 ± 19), (18 ± 5) and (38 ± 7), respectively. The number of 3AO cell was (19 ± 4), (134 ± 20), (12 ± 3) and (58 ± 11), respectively. The results showed that the number of cells in FSH group was significantly higher than that in control group (P < 0.05), while the number of cell in FSH + LY294002 group was significantly fewer than that in FSH group (P < 0.05). (4) There was no significant difference in the expression of FSHR and Akt1/2 between FSH group and control group (P > 0.05), but FSH increased the expression of p-Akt and the ratio of NF-κB p65 in the nucleus versus cytoplasm in SKOV3 and 3AO cells, there were significant differences compared with control group (P < 0.05). LY294002 reversed the effects of FSH on increasing the expression of p-Akt and the ratio of NF-κB p65 in the nucleus versus cytoplasm, there were significant differences among LY294002 group, FSH + LY294002 group and FSH group (P < 0.05). CONCLUSION: The effects of FSH on proliferation and invasion of ovarian cancer cell lines SKOV3 and 3AO may be realized by regulating the activity of NF-κB in PI3K/Akt signal pathway.

The state-dependent impulsive control for a general predator-prey model.

In this paper, a general predator-prey model with state-dependent impulse is considered. Based on the geometric analysis and Poincaré map or successor function, we construct three typical types of Bendixson domains to obtain some sufficient conditions for the existence of order-1 periodic solutions. At the same time, the existing domains are discussed with respect to the system parameters. Moreover, the Analogue of Poincaré Criterion is used to obtain the asymptotic stability of the periodic solutions. Finally, to illustrate the results, an example is presented and some numerical simulations are carried out.

Associations Between Poor Oral Hygiene and Risk of Pancreatic Cancer: A Meta-analysis of Observational Studies.

OBJECTIVES: Epidemiological studies have reported the association of poor oral hygiene, especially periodontal disease, and tooth loss with the risk of pancreatic cancer (PC). However, these studies have yielded inconsistent results. Therefore, this systematic review and meta-analysis aimed to investigate the relationship between oral disease and PC. METHODS: We systematically searched the PubMed, Embase, and Cochrane Library databases for English literature since inception through May 2021. We used relative risks, hazard ratios, or odds ratios to measure the association between oral disease and PC. A fixed- or random-effects model was applied to evaluate pooled risk estimates, and sensitivity and subgroup analyses were performed to identify sources of heterogeneity and pooled estimation. RESULTS: We identified 17 relevant observational studies involving 1,352,256 participants. Notably, oral disease correlated significantly with PC (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.13-1.54). In subgroup analyses, subjects with periodontal disease (HR, 1.38; 95% CI, 1.12-1.71) had a higher risk of developing PC than those with tooth loss (HR, 1.19; 95% CI, 0.97-1.46). CONCLUSIONS: The results suggest that subjects with oral disease may face a significant and independent risk of PC. However, the mechanisms linking oral disease and PC are uncertain, and additional investigations of this correlation are warranted.