Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION: PROSPERO registration number: CRD42023415198.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome.

Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese medicinal plants showing a tight correlation with gut microbiota. Polycystic ovary syndrome (PCOS) is a prevalent reproductive and endocrine disorder syndrome among women of childbearing age. Dysbiosis, the imbalance of intestinal microorganisms, is a potential factor that takes part in the pathogenesis of PCOS. Recent evidence indicates that berberine offers promise for treating PCOS. Here, we review the recent research on the interaction between berberine and intestinal microorganisms, including the changes in the structure of gut bacteria, the intestinal metabolites after BBR treatment, and the effect of gut microbiota on the bioavailability of BBR. We also discuss the therapeutic effect of BBR on PCOS in terms of gut microbiota and its potential mechanisms.

The role of insulin-like growth factor 2 mRNA binding proteins in female reproductive pathophysiology.

Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs) family belongs to a highly conserved family of RNA-binding proteins (RBPs) and is responsible for regulating RNA processing including localization, translation and stability. Mammalian IMPs (IMP1-3) take part in development, metabolism and tumorigenesis, where they are believed to play a major role in cell growth, metabolism, migration and invasion. IMPs have been identified that are expressed in ovary, placenta and embryo. The up-to-date evidence suggest that IMPs are involved in folliculogenesis, oocyte maturation, embryogenesis, implantation, and placentation. The dysregulation of IMPs not only contributes to carcinogenesis but also disturbs the female reproduction, and may participate in the pathogenesis of reproductive diseases and obstetric syndromes, such as polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM) and gynecological tumors. In this review, we summarize the role of IMPs in female reproductive pathophysiology, and hope to provide new insights into the identification of potential therapeutic targets.

MicroRNA let-7i inhibits granulosa-luteal cell proliferation and oestradiol biosynthesis by directly targeting IMP2.

RESEARCH QUESTION: Increased granulosa cell division is associated with abnormal folliculogenesis in polycystic ovary syndrome (PCOS). Lethal-7i microRNA (let-7i) may play an important role in the follicular development and granulosa cell growth; therefore is let-7i involved in PCOS pathogenesis? DESIGN: The expression of let-7i was measured in granulosa-luteal cells (GLC) from women with or without PCOS. A human granulosa cell line, KGN, was used for the functional study. Mimics and inhibitors of let-7i, lentiviruses expressing insulin-like growth factor 2 mRNA binding protein (IMP2), and small-interfering RNAs were transfected into KGN cells. KGN cell proliferation was determined by 5-ethynyl-2'-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays. The cell cycle and apoptosis were assessed by propidium iodide-annexin V (PI-A) staining and fluorescence-activated cell sorting. Oestradiol concentration was determined by enzyme-linked immunoassay. Bioinformatics analysis and luciferase reporter assay were applied to confirm the let-7i target genes. RESULTS: The study showed that let-7i was down-regulated in PCOS GLC (P = 0.001). Mimics of let-7i inhibited KGN proliferation (P = 0.001), and decreased aromatase expression (P = 0.030) and oestradiol production (P = 0.029), whereas let-7i inhibitors had the opposite effect. Bioinformatics analysis and quantitative real-time (qRT) PCR identified IMP2 as a target of let-7i (P = 0.021). qRT-PCR and western blot analysis indicated that IMP2 was up-regulated in GLC in women with PCOS (P = 0.001 and P = 0.044), and IMP2 expression was suppressed by let-7i in KGN cells (P < 0.001). Luciferase reporter assay results (P = 0.002), combined with the rescue assay, confirmed that let-7i inhibited KGN cell proliferation and reduced oestradiol concentration by directly targeting IMP2. CONCLUSIONS: let-7i was down-regulated in PCOS GLC. Overexpression of let-7i inhibited KGN cell proliferation and decreased oestradiol production in an IMP2-dependent manner, providing a new molecular mechanism for PCOS.

Critical role of PAFR/YAP1 positive feedback loop in cardiac fibrosis.

Aberrant activation of cardiac fibroblasts is the main cause and character of cardiac fibrosis, and inhibition of cardiac fibrosis becomes a promising treatment for cardiac diseases. Platelet-activating factor (PAF) and Hippo pathway is recently recognized as key signaling mechanisms in cardiovascular diseases. In this study we explored the potential roles of PAF and Hippo signaling pathway in cardiac fibrosis. Myocardial infarction (MI) was induced in mice by left anterior descending artery ligation. After 28 days, the mice were sacrificed, and the hearts were collected for analyses. We showed that PAF receptor (PAFR) and yes-associated protein 1 (YAP1, a key effector in the Hippo pathway) were significantly increased in the heart of MI mice. Increased expression of PAFR and YAP1 was also observed in angiotensin II (Ang II)-treated mouse cardiac fibroblasts. In mouse cardiac fibroblasts, forced expression of YAP1 increased cell viability, resulted in collagen deposition and promoted fibroblast-myofibroblast transition. We showed that PAF induced fibrogenesis through activation of YAP1 and promoted its nuclear translocation via interacting with PAFR, while YAP1 promoted the expression of PAFR by binding to and activating transcription factor TEAD1. More importantly, silencing PAFR or YAP1 by shRNA, or using transgenic mice to induce the conditional deletion of YAP1 in cardiac fibroblasts, impeded cardiac fibrosis and improved cardiac function in MI mice. Taken together, this study elucidates the role and mechanisms of PAFR/YAP1 positive feedback loop in cardiac fibrosis, suggesting a potential role of this pathway as novel therapeutic targets in cardiac fibrosis.

Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease of the female reproductive system that seriously affects women's health. Berberine (BBR) has many pharmacological properties and is used as an insulin sensitizer. This study aimed to investigate the effect of BBR on PCOS and explore its related mechanisms. METHODS: Forty-two rats were randomly divided into the following six groups (n = 7 per group): control, control + BBR, PCOS-normal diet (ND), PCOS-ND + BBR, PCOS-high-fat diet (HFD), and PCOS-HFD + BBR. The PCOS rat models were established by injecting rats with dehydroepiandrosterone. Further, the rats were gavaged with BBR (150 mg/kg/d) for 6 weeks. Then, the body weight, HOMA-IR, and testosterone levels of all rats were determined. Cell apoptosis of ovary granulosa cells was determined by a TUNEL assay kit. Real-time quantification PCR (RT-qPCR) and western blotting were utilized to evaluate the expression of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3. RESULTS: BBR reduced the levels of insulin resistance and testosterone in PCOS rats. Additionally, the cell apoptosis rate increased significantly in PCOS rats (P < 0.05) and decreased after BBR treatment (P < 0.05). The results of RT-qPCR and western blotting showed that the expression levels of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3 significantly increased in PCOS rats, while BBR suppressed their expression levels. CONCLUSIONS: BBR may relieve PCOS pathology and IR values by inhibiting cell apoptosis and by regulating the expression levels of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3.

Estrogen-dependent KCa1.1 modulation is essential for retaining neuroexcitation of female-specific subpopulation of myelinated Ah-type baroreceptor neurons in rats.

Female-specific subpopulation of myelinated Ah-type baroreceptor neurons (BRNs) in nodose ganglia is the neuroanatomical base of sexual-dimorphic autonomic control of blood pressure regulation, and KCa1.1 is a key player in modulating the neuroexcitation in nodose ganglia. In this study we investigated the exact mechanisms underlying KCa1.1-mediated neuroexcitation of myelinated Ah-type BRNs in the presence or absence of estrogen. BRNs were isolated from adult ovary intact (OVI) or ovariectomized (OVX) female rats, and identified electrophysiologically and fluorescently. Action potential (AP) and potassium currents were recorded using whole-cell recording. Consistently, myelinated Ah-type BRNs displayed a characteristic discharge pattern and significantly reduced excitability after OVX with narrowed AP duration and faster repolarization largely due to an upregulated iberiotoxin (IbTX)-sensitive component; the changes in AP waveform and repetitive discharge of Ah-types from OVX female rats were reversed by G1 (a selective agonist for estrogen membrane receptor GPR30, 100 nM) and/or IbTX (100 nM). In addition, the effect of G1 on repetitive discharge could be completely blocked by G15 (a selective antagonist for estrogen membrane receptor GPR30, 3 µM). These data suggest that estrogen deficiency by removing ovaries upregulates KCa1.1 channel protein in Ah-type BRNs, and subsequently increases AP repolarization and blunts neuroexcitation through estrogen membrane receptor signaling. Intriguingly, this upregulated KCa1.1 predicted electrophysiologically was confirmed by increased mean fluorescent intensity that was abolished by estrogen treatment. These electrophysiological findings combined with immunostaining and pharmacological manipulations reveal the crucial role of KCa1.1 in modulation of neuroexcitation especially in female-specific subpopulation of myelinated Ah-type BRNs and extend our current understanding of sexual dimorphism of neurocontrol of BP regulation.

Pyroptosis and inflammasomes in obstetrical and gynecological diseases.

Pyroptosis, an inflammatory form of programmed cell death, takes an essential part in a wide variety of physiological activities, for instance, implantation, placentation and the body's defense against infection. However, once excessively activated, pyroptosis mediated by the activation of inflammasomes can be highly pathological. It can cause inflammatory and autoimmune diseases including a variety of obstetrical and gynecological diseases, such as endometriosis, gestational diabetes mellitus, insulin resistance in polycystic ovary syndrome, and multiple obstetric complications including preeclampsia. Although the role of pyroptosis in the pathogenesis of the above mentioned diseases has not been fully elucidated, we try to tap its therapeutic potential by targeting pyroptosis signaling and inflammasome formation. Pyroptosis and inflammasomes are confirmed to be involved in endometriosis and gynecological malignant tumors, therefore, medical approachs inducing pyroptosis of the ectopic endometrium and tumor cells can be feasible treatments for endometriosis and gynecological cancers. On the maternal-fetal interface, although a certain level of the innate immune response activation is required for a successful implantation and placentation, maternal and fetal injury may occur once the inflammasomes are over-activated. Besides, since gestational diabetes mellitus and insulin resistance in polycystic ovary syndrome share common pathogenesis with metabolic diseases, this domain research sheds light on future study of some obstetrical and gynecological diseases.

Berberine Improves the Symptoms of DHEA-Induced PCOS Rats by Regulating Gut Microbiotas and Metabolites.

OBJECTIVES: The aim of this study was to investigate the effects of berberine on polycystic ovary syndrome (PCOS) with insulin resistance (IR). DESIGN: This study performed 16S rRNA sequencing and metabolomic analysis on dehydroepiandrosterone (DHEA)-induced PCOS rats treated with berberine, focusing on the improvement of PCOS-IR by modifying gut microbiota and metabolism. METHODS: Forty-two female Sprague Dawley rats were randomly divided into 4 experimental groups of 8 rats each (PCOS + HFD, PCOS + HFD + BBR, NCD + PCOS, and NCD + PCOS + BBR groups). Homeostasis model assessment of insulin resistance (HOMA-IR) index-related indicators and hormone level in serum were analyzed. 16S rRNA sequencing and metabolomic analysis were performed on DHEA-induced PCOS rats treated with berberine. In addition, the differential microbiotas and metabolites were screened. Also, enrichment analysis was carried out on the differential metabolites. Finally, we constructed a correlation network to analyze the correlation between differential microbiotas and metabolites. RESULTS: Firmicutes and Bacteroidetes were changed at the phylum level, and Romboutsia, Bacteroides, and Clostridium_sensu_stricto_1 were changed at the genus level after berberine treatment. In addition, a total of 26 differential operational taxonomic units and 3 metabolites (glutamine, unsaturated acids [CH = CH], and glucose) between 2 groups were obtained. Moreover, these metabolites were mainly involved in type 2 diabetes mellitus, 2-component system, and ABC transporter Kyoto Encyclopedia of Genes and Genomes pathways. And, 3 microbiotas (Lachnospiraceae_NC2004_group, Flavonifractor, and Parasutterella) were regulated by glucose and glutamine. LIMITATIONS: The sample size involved in this study is relatively small. In addition, relevant experiments need to be performed to verify the obtained results from this study, and in-depth functional studies are needed. CONCLUSIONS: Berberine is effective in improving the pathological condition in PCOS by regulating the gut microbiotas and metabolites. This study will provide evidence for therapeutic efforts to treat PCOS-IR using berberine.

Ovarian hyperstimulation syndrome: a clinical retrospective study on 565 inpatients.

The aim of this study was to analyze clinical manifestations of 565 ovarian hyperstimulation syndrome (OHSS) inpatients in the largest Obstetrics and Gynecology hospital in China from year 2010 to 2017, to get more understanding of epidemiologic features of this disease, and to provide some insight on the diagnosis, treatment, and preventions of OHSS. It is a clinical retrospective study. In the 565 cases that developed OHSS over an eight-year period between 2010 and 2017 were reviewed, we assessed patients' general characteristics, clinical manifestations, treatment, prognosis, and the relationship between different indicators and the severity of OHSS. Totally 12 kinds of ovulation induction protocols (Protocol 1: CC; Protocol 2: Gn; Protocol 3: hCG; Protocol 4: GnRh-a; Protocol 5: CC & Gn; Protocol 6: CC & hCG; Protocol 7: Gn & hCG; Protocol 8: GnRh-a & Gn; Protocol 9: CC & Gn & hCG; Protocol 10: GnRh-a & CC & Gn; Protocol 11: Letrozole & Gn & hCG; Protocol 12:GnRh-a & Letrozole & Gn) were analyzed and the Odds Ratio (OR) of each protocol were calculated. Five hundred and sixty-five patients were reviewed in our study. In all these patients, the number of hospitalizations, mean age, primary infertility rate, and pregnancy rate did not differ through the last 8 years. From which we may infer that the incidence rate of OHSS may not change over the last 8 years. Older patients tend to develop into more severe stage easily. The pregnancy rate was much lower in mild stage patients, but no difference was found between patients in moderate, severe and critical stage. Oocytes retrieval is strongly associated with severity. PCOS history, irregular menstrual cycle and infertility type do not seem to affect the severity of OHSS. Twelve kinds of ovulation induction protocols were analyzed, OR of different protocols were calculated, what is noteworthy is that patients who used GnRh easily developed more severe OHSS than the patients who received oocytes retrieval. We suggest that we may choose ovulation induction protocols according to the OR table while treating women with high-risk factors.

Ultrasound elastography: a novel tool for the differential diagnosis of pleural effusion.

INTRODUCTION: Traditional thoracic ultrasound (TUS) is often the initial tool used to help diagnose malignant pleural effusion (MPE). Ultrasound elastography, a relatively new technique, has been used to differentiate malignant disease from benign disease by evaluating tissue "stiffness". However, no studies evaluating the efficacy of ultrasound elastography for diagnosing MPE are available. We assessed the value of ultrasound elsatography for diagnosing MPE prospectively. METHODS: All 244 enrolled patients were divided into a development set and a validation set in chronological order. The cut-off elasticity index was established using a receiver operating characteristic curve constructed from the continuous data of the patients in the development set. The diagnostic performance of ultrasound elastography was compared with that of TUS in the validation set. RESULTS: In the development set, the mean elasticity index (47.25 kPa) was the optimal cut-off. In the validation set, pleural ultrasound elastography had a sensitivity of 83.64%, a specificity of 90.67%, a positive predictive value of 86.79%, a negative predictive value of 88.31%, a positive likelihood ratio of 8.96 and a negative likelihood ratio of 0.18 for diagnosing MPE. The sensitivity of ultrasound elastography was significantly higher (p=0.006) than that of TUS (60%). CONCLUSION: Pleural ultrasound elastography is a better technique than TUS for differentiating MPE from benign pleural disease.

A decision tree built with parameters obtained by computed tomographic pulmonary angiography is useful for predicting adverse outcomes in non-high-risk acute pulmonary embolism patients.

BACKGROUND: Acute pulmonary embolism (APE) is one of the leading causes of death in cardiovascular disease. The 30-day mortality can still be 1.7-15% in non-high-risk APE patients. Some non-high-risk patients can progress into the high-risk group and even die, which is referred to as an adverse outcome. Promoting the diagnosis and predictive ability of adverse short-term prognosis was still a problem that needed to be solved. Computed tomography pulmonary angiography (CTPA) may be a way to promote the predictive ability. Our aim to develop predictive tools based on parameters obtained by computed tomographic pulmonary angiography (CTPA) in the form of a decision tree for use in non-high-risk acute pulmonary embolism (APE) patients. METHODS: Adverse outcome was defined within 30 days after admission to the hospital. A decision tree was built to predict adverse outcomes based on discriminating factors screened from cardiac volume and clot characteristics from recursive partitioning analysis and compared with simplified pulmonary embolism severity index (sPESI), Bova scores and risk stratification. The area under the receiver operating characteristic curve (ROC-AUC) was used to confirm the predictive ability. RESULTS: A total of 38 patients with and 303 patients without adverse outcomes were enrolled. Right ventricular/left ventricular (RV/LV) volume ratio, central pulmonary artery (CPA) embolism and right atria/left atria (RA/LA) volume ratio were used as splits in the decision tree to predict adverse outcomes in all patients. The ROC-AUC was 0.858. In CPA embolism patients, a recursive partitioning analysis was performed with cardiac volume and novel clot burden, but only the obstructing area (OA) ratio was included as a discriminating factor to build a second decision tree. The ROC-AUC for the second decision tree was 0.810. The decision trees were superior to those of sPESI, Bova scores and risk stratification, and there were no significant differences between the two decision trees. CONCLUSIONS: A decision tree built by CTPA parameters can predict adverse outcomes in non-high-risk APE patients.

Bu-Shen-Yi-Qi formula impairs cytotoxicity of NK cells by up-regulating IDO expression in trophoblasts.

Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could modulate immune condition at maternal-fetal interface via its effect on trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46 expression on NK cells were measured by flow cytometry (FCM). In this study, we found that herb medium could increase the IDO expression at appropriate concentrations. As an inhibitor of IDO, 1-MT could impair the inhibitory function of trophoblasts on NK cells. Furthermore, Bu-Shen-Yi-Qi formula could enhance the inhibitory function of trophoblasts on NK cells. In conclusion, Bu-Shen-Yi-Qi formula can inhibit NK cytotoxicity by up-regulating IDO expression in trophoblasts and play a role in the treatment of URSA patients.

Rapid on-site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room.

INTRODUCTION: Patients with acute pulmonary embolism(APE)who present with right ventricular dysfunction (RVD) have a worse prognosis. This study aimed to evaluate the value of routine biochemical parameters in predicting RVD and 30-day mortality in patients with APE. METHODS: We retrospectively collected the clinical data for 154 enrolled patients, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), D-dimer, cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP). We analyzed the correlation between RVD and the parameters and conducted a receiver operating characteristic (ROC) curve to confirm the cut-off values for predicting RVD and 30-day mortality. Formulas were built with relevant parameters to predict RVD and 30-day mortality. RESULTS: Age, NLR, PLR, D-dimer, the ratio of cTnI (+), and NT-proBNP (+) were significantly higher in RVD (+) patients. The ratio of cTnI (+) and NT-proBNP (+) in 30-day mortality (+) patients was significantly higher than that in 30-day mortality (-) patients. According to the logistic regression analysis, NLR, cTnI (+), and NT-proBNP (+) correlated with RVD. The formula for the RVD risk score is 0.072 × NLR+1.460 × NT-proBNP (+)+2.113 × cTnI (+), and the area under the curve (AUC) = 0.890 (95% CI: 0.839-0.941, P = .001). The formula for the 30-day mortality risk score is 0.115 × NLR + 2.046 × NT-proBNP (+) + 1.946 × cTnI (+) -0.016 × PLR, and the AUC = 0.903 (95% CI: 0.829-0.976, P = .001). CONCLUSIONS: The rapid on-site evaluation of routine biochemical parameters, including NLR, cTnI, and NT-proBNP levels, and the formula developed using these parameters are valuable for predicting RVD and 30-day mortality in patients with APE.

[Effect of different concentrations of Gegen Qinlian decoction on expression of P-glycoprotein and multi-drug resistance protein transporter in Caco-2 cells].

To investigate the effects of Gegen Qinlian decoction on the expression of P-glycoprotein (P-gp) and multi-drug resistance protein (MRP) in epithelial cells of human colon adenocarcinoma Caco-2 cells．The effects of different concentrations of Gegen Qinlian decoction on the expression levels of p-gp and MRP1-6 mRNA in Caco-2 cells were detected by real time quantitative reverse transcriptase PCR (qRT-PCR).12 h after drug treatment (5.00 g·L⁻¹), the expression levels of MDR1 and MRP1-6 were significantly down-regulated at concentration of 5.00 g·L⁻¹; the mRNA expression levels of MDR1，MRP1，MRP2，MRP4，MRP5 and MRP6 were significantly down-regulated at concentration of 2.50 g·L⁻¹; only the expression levels of MRP2 and MRP5 were significantly affected at concentration of 1.00 g·L⁻¹. The results showed that the expression levels of MDR1 and MRP1-6 mRNA in Caco-2 cells could be down-regulated in a dose-dependent manner. Gegen Qinlian decoction may reduce drug efflux by down-regulating the mRNA expression of cell transporters in Caco-2 cell, and increase the time of drug action, thereby enhancing the bioavailability of chemotherapeutic drugs.

Diagnostic Value of Cerebrospinal Fluid T-SPOT.TB for Tuberculousis Meningitis in China.

The aim of this study was to evaluate the diagnostic value of the cerebrospinal fluid (CSF) T-SPOT.TB test for the diagnosis of TB meningitis (TBM). A retrospective analysis of 96 patients with manifested meningitis was conducted; T-SPOT.TB test was performed for diagnosing TBM to determine the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A receiver operating characteristic (ROC) curve was also drawn to assess the diagnostic accuracy. The sensitivity, specificity, PPV, and NPV of CSF T-SPOT.TB test were 97.8%, 78.0%, 80.3%, and 97.5%, respectively, for 52 patients (54.2%) of the 96 enrolled patients. The area under the curve (AUC) was 0.910, and the sensitivities of CSF T-SPOT.TB for patients with stages I, II, and III of TBM were 96.7%, 97.2%, and 98.9%, respectively. CSF T-SPOT.TB test is a rapid and accurate diagnostic method with higher sensitivity and specificity for diagnosing TBM.

The clinical experience of robot-assisted surgery in gynecologic cancer.

The comparison of robotic and conventional laparoscopic hysterectomy and pelvic lymphadenectomy in gynecologic cancer still needs to be studied. In all, 98 consecutive cases of patients with gynecologic cancer undergoing robot-assisted hysterectomy and pelvic lymphadenectomy, and another 98 consecutive cases of conventional laparoscopic hysterectomy and pelvic lymphadenectomy during the same period in the Obstetrics and Gynecology Hospital of Fudan University were included. The duration of the operation, blood loss, drainage during the first 24 h after the operation, total hospital stay, hospital stay after the operation, lymph nodes collected, perioperative complications, and the cost of each operation for both procedures were recorded. The duration of the operation was longer, and the cost of each operation was almost seven times higher in the robot group than that in the conventional laparoscopy group. But the differences with regard to blood loss, drainage during the first 24 h after the operation, total hospital stay, hospital stay after operation, the lymph nodes collected, and the rate of perioperative complications were not statistically significant. Robot-assisted surgery (RAS) in gynecologic cancer is as feasible as conventional laparoscopic surgery. We recommend further studies about the cost and effect of RAS in gynecologic cancer.

[In vitro and in vivo intestinal absorption of Huanglian decoction in multi-component environment].

The effect of drugs in the body is always inseparable with the dynamic processes of absorption, distribution, metabolism and excretion. For oral drug, absorption, as the first link to enter the body, is particularly valued. Traditional Chinese medicine has multiple components and multiple targets, and the nature of its single composition is different from that in the multicomponent environment. Alkaloids in Huanglian extract was used as the main object in this study to establish an analytical method for determining the content of alkaloids in Huanglian. In addition, the compositions of the Huanglian aqueous extract solution which can be absorbed through intestinal wall into blood, were initially determined by the means of everted gut sac and in intestinal perfusion with venous sampling experiment. This paper can provide data reference and support for the further study on the absorption and metabolism of Huanglian.