Photoelectrochemical Asymmetric Catalysis Enables Enantioselective Heteroarylcyanation of Alkenes via C-H Functionalization.

The asymmetric difunctionalization of alkenes, a method transforming readily accessible alkenes into enantioenriched chiral structures of high value, has long been a focal point of organic synthesis. Despite tremendous efforts in this domain, it remains a considerable challenge to devise enantioselective oxidative dicarbofunctionalization of alkenes, even though these transformations can utilize stable and unfunctionalized functional group donors. In this context, we report herein a photoelectrocatalytic method for the enantioselective heteroarylcyanation of aryl alkenes, which employs unfunctionalized heteroarenes through C-H functionalization. The photoelectrochemical asymmetric catalysis (PEAC) method combines photoredox catalysis and asymmetric electrocatalysis to facilitate the formation of two C-C bonds operating via hydrogen (H2) evolution and obviating the need for external chemical oxidants.

Efficacy and safety of high-dose intramuscular vitamin D2 injection in type 2 diabetes mellitus with distal symmetric polyneuropathy combined with vitamin D insufficiency: study protocol for a multicenter, randomized, double-blinded, and placebo-controlled trial.

Background: Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency. Methods and analysis: We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D2 supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months post-intervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D2 and 25(OH)D3 levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation. Discussion: Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of HDVD supplementation for patients with T2DM and DSPN and will provide new ideas for pharmacological research and clinical treatment of diabetic neuropathy. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2200062266.

Accuracy of Mean Value of Central Venous Pressure from Monitor Digital Display: Influence of Amplitude of Central Venous Pressure during Respiration.

Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.

Photoelectrochemical Asymmetric Catalysis Enables Direct and Enantioselective Decarboxylative Cyanation.

The development of efficient and sustainable methods for decarboxylative transformations is of great importance due to the ease of availability and nontoxicity of carboxylic acids. Despite tremendous efforts in this area, it remains challenging to develop enantioselective transformations direct from carboxylic acids. Herein we disclose a photoelectrocatalytic method for the direct and enantioselective decarboxylative cyanation. The photoelectrochemical reactions convert carboxylic acids to enantioenriched nitriles by employing cerium/copper relay catalysis with a cerium salt for catalytic decarboxylation and a chiral copper complex for stereoselective C-CN formation.

Meta-Study of the Clinical Effect of Conservative Treatment in Uterine Fibroids.

Heavy menstrual bleeding (HMB), distress in the pelvis, infertile, and stressed feelings are all indications of fibroids in the uterus, the most prevalent type of benign uterine tumor. Nearly one-third of women with fibroid in the uterus seek medical help. The goal of this analysis is for a better understanding of the mechanisms that relate fibroids to these symptoms and to assess several treatment options, including the application of the gonadotropin-releasing hormone (GnRH) antagonist. We compiled the commonest as well as appropriate studies on the most common symptom of fibroids, as well as medicinal and surgical treatment options. Those who said they used GnRH antagonists orally were probed further. The underlying mechanisms myoma-caused menorrhagia as well as sterility were examined since those have been critical to understand the detailed mechanism as well as the targeted treatment modality. New treatments are determined by the amount, dimension cum localization of fibroids, and the women's age and also her choice on future childbirth. Myomas have considerable economic consequences with respect to direct expenditure, wage losses, as well as difficulties. In this context, medical, surgical, and nonsurgical techniques were examined. The novelty applied in this research article is the implementation of the GnRH antagonist-based methodology for the removal of fibroids in the uterine layer. The methodology is superior to the existing techniques for the treatment of fibroids in the uterine membrane. Novel medical techniques including GnRH antagonists were investigated and proved to be a viable new option. Alternatives to surgical-surgical modalities are desperately needed, specifically for those who are looking forward for future childbirth. GnRH antagonists have been shown to effectively alleviate the symptoms of fibroids and welcome new techniques for myoma treatment.

Effect of Mirena placement on reproductive hormone levels at different time intervals after artificial abortion.

BACKGROUND: Improper methods of contraception greatly increase the risk of abortion, cervical or endometrial lesions, and the number of recurrent artificial abortions. These complications result in the deterioration of a patient's outcome. Further, the proportion of artificial abortions is highest among unmarried females. Placement of an intrauterine device, such as the Mirena, after an artificial abortion may decrease the likelihood of an endometrial injury caused by recurrent abortions while significantly improving its contraceptive effects. AIM: To discuss the effect of Mirena placement on reproductive hormone levels at different time points after an artificial abortion. METHODS: Women (n = 119) undergoing an artificial abortion operation were divided into the study (n = 56) and control (n = 63) groups. In the study group, the Mirena was inserted immediately after the artificial abortion, whereas in the control group, it was inserted 4-7 d after the onset of the first menstrual cycle after abortion. All participants were followed-up for 6 mo to observe the continuation and expulsion rates and adverse reactions and to measure the levels of serum estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS: The continuation rates were 94.64% and 93.65% in the study group and the control group, respectively. The expulsion rates were 1.79% and 3.17% in the study group and the control group, respectively. There was no statistically significant difference between the two groups (P > 0.05). There were also no statistically significant differences in the proportion of patients with bacterial vaginitis, trichomonas vaginitis, or cervicitis between the groups (P > 0.05). Six months after Mirena placement, E2 Levels were 45.50 ± 7.13 pg/mL and 42.91 ± 8.10 pg/mL, FSH 13.60 ± 3.24 mIU/mL and 14.54 ± 3.11 mIU/mL, and LH 15.11 ± 2.08 mIU/mL and 14.60 ± 3.55 mIU/mL in the study and control groups, respectively. There were no significant differences in hormone levels between the two groups (P > 0.05). There were also no statistically significant differences in the proportions of abnormal menstruation, prolonged menstruation, or pain during intercourse between the study and control groups after Mirena placement (P > 0.05). There were no statistically significant differences in uterine volume, sexual desire, sexual activity, or the sexual satisfaction score between the study and control groups before and after Mirena placement (P > 0.05). CONCLUSION: Placement of a Mirena intrauterine device immediately after an artificial abortion does not increase the risk of adverse reactions and can help prevent endometrial injury caused by recurrent abortions.

CircHIPK3 modulates VEGF through MiR-7 to affect ovarian cancer cell proliferation and apoptosis.

PURPOSE: The purpose of this study was to observe the effects of circHIPK3on the proliferation and apoptosis of ovarian cancer cells, and to further explore the potential mechanism therein. METHODS: CircHIPK3 was determined in the carcinoma tissues, normal adjacent tissues, and also in ovarian cancer cells via RT-PCR. The proliferation and apoptosis of cells were observed via colony-forming assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and Western blotting. Moreover, the effect of the inhibition of circHIPK3 on the in vivo growth of ovarian cancer cells was detected using subcutaneous tumorigenesis assay. Finally, the effect of circHIPK3 on the expression of the micro ribonucleic acid (miR)-7/vascular endothelial growth factor (VEGF) signaling pathway in ovarian cancer cells was examined. RESULTS: CircHIPK3 in the carcinoma tissues was obviously higher than that in normal adjacent tissues. SKOV3 cell lines transfected with circHIPK3 inhibitor exhibited declined number of colonies. The inhibition of circHIPK3 distinctly suppressed the expression of B-cell lymphoma 2 (Bcl-2) and raised that of Bcl-2 associated X protein (Bax). Besides, the inhibition of circHIPK3 obviously weakened the tumorigenicity of ovarian cancer cells subcutaneously transplanted. Finally, it was found that miR-7 declined obviously and VEGF rose distinctly in the carcinoma tissues, and the in vitro assay verified the obvious increase in the expression of miR-7 and the prominently inhibited VEGF protein expression in the ovarian cancer cells with the inhibition of circHIPK3. CONCLUSIONS: CircHIPK3 has an obviously increased expression level in the carcinoma tissues of ovarian cancer patients, and the inhibition of circHIPK3 can activate the miR-7-mediated decline in the expression of VEGF to repress the proliferation and promote the apoptosis of ovarian cancer cells.

Site-Selective Electrochemical Benzylic C-H Amination.

C-H/N-H cross-coupling is an ideal strategy to synthesize various amines but remains challenging owing to the requirement for sacrificial chemical oxidants and the difficulty in controlling the regio- and chemo-selectivity. Herein we report a site-selective electrochemical amination reaction that can convert benzylic C-H bonds into C-N linkages via H2 evolution without need for external oxidants or metal catalysts. The synthetic strategy involves anodic cleavage of benzylic C-H to form a carbocation intermediate, which is then trapped with an amine nucleophile leading to C-N bond formation. Key to the success is to include HFIP as a co-solvent to modulate the oxidation potentials of the alkylbenzene substrate and the aminated product to avoid overoxidation of the latter.

Continuous renal replacement therapy rescues severe haemorrhagic fever with renal syndrome in pregnancy: a case report.

BACKGROUND: Haemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease caused by various types of viruses of the genus Hantavirus, which are mainly transmitted by contact with the infected rodents and their droppings. Pregnancy complicated with HFRS is rare; however, adverse maternal and foetal outcomes may be noted. In this report, we describe a case involving a pregnant woman with HFRS who was in a state of multiple organ dysfunction syndrome (MODS) and was successfully treated with continuous renal replacement therapy (CRRT). CASE PRESENTATION: A 32-year-old pregnant woman at 29 weeks of gestation was hospitalised for a fever and upper respiratory tract infection due to HFRS in winter. Persistent fever, coagulation disorder, thrombocytopenia, electrolyte imbalance, abnormal liver function, and renal failure were noted during the progression of the disease. The patient was treated with CRRT. She recovered after 21 days, and delivered a live infant by caesarean section at 38 weeks of gestation. Furthermore, obvious abnormalities were not detected during the follow-up of the mother and infant at 42 days, 3 months, 6 months, and 1 year after the delivery. CONCLUSIONS: Early diagnosis, timely application of CRRT, and comprehensive treatment may be essential for the successful treatment of patients with HFRS during pregnancy.

Electrophotocatalytic Decarboxylative C-H Functionalization of Heteroarenes.

Decarboxylative C-H functionalization reactions are highly attractive methods for forging carbon-carbon bonds considering their inherent step- and atom-economical features and the pervasiveness of carboxylic acids and C-H bonds. An ideal approach to achieve these dehydrogenative transformations is through hydrogen evolution without using any chemical oxidants. However, effective couplings by decarboxylative carbon-carbon bond formation with proton reduction remain an unsolved challenge. Herein, we report an electrophotocatalytic approach that merges organic electrochemistry with photocatalysis to achieve the efficient direct decarboxylative C-H alkylation and carbamoylation of heteroaromatic compounds through hydrogen evolution. This electrophotocatalytic method, which combines the high efficiency and selectivity of photocatalysis in promoting decarboxylation with the superiority of electrochemistry in effecting proton reduction, enables the efficient coupling of a wide range of heteroaromatic bases with a variety of carboxylic acids and oxamic acids. Advantageously, this method is scalable to decagram amounts, and applicable to the late-stage functionalization of drug molecules.

Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1.

BACKGROUND: The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what's more its potential mechanism. METHODS: The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the "mixOmics" R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented. RESULTS: MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells. CONCLUSION: Our study indicated the effects of XIST/miR-140-5p/ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.

The effect of variable arterial transducer level on the accuracy of pulse contour waveform-derived measurements in critically ill patients.

We know that a 10 cm departure from the reference level of pressure transducer position is equal to a 7.5 mmHg change of invasive hemodynamic pressure monitoring in a fluid-filled system. However, the relationship between the site level of a variable arterial pressure transducer and the pulse contour-derived parameters has yet to be established in critically ill patients. Moreover, the related quantitative analysis has never been investigated. Forty-two critically ill patients requiring PiCCO-Plus cardiac output monitoring were prospectively studied. The phlebostatic axis was defined as the zero reference level; the arterial pressure transducer was then vertically adjusted to different positions (+5, +10, +15, +20, -20, -15, -10, -5 cm) of departure from the zero reference site. The pulse contour waveform-derived parameters were recorded at each position. Elevation of the pressure transducer caused significantly positive changes in the continuous cardiac index (+CCI), stroke volume index (+SVI), and stroke volume variation (+SVV), and negative changes in the rate of left ventricular pressure rise during systole (-dP/dtmax), the systemic vascular resistance index (-SVRI), and vice versa. At the 5 cm position, the SVRI changes reached statistical significance with error. At the 10 cm position, the changes in CCI and dP/dtmax reached statistical significance with error, while the change in SVV reached statistical significance at 15 cm. The change rate of CCI was more than 5 % at the 15 cm position and approximately 10 % at the 20 cm position. On average, for every centimeter change of the transducer, there was a corresponding 0.014 L/min/m(2) CCI change and 0.36 % change rate, a 1.41 mmHg/s dP/dtmax change and 0.13 % change rate, and a 25 dyne/s/cm(5) SVRI change and 1.2 % change rate. The variation of arterial transducer position can result in inaccurate measurement of pulse contour waveform-derived parameters, especially when the transducer's vertical distance is more than 10 cm from the phlebostatic axis. These findings have clinical implications for continuous hemodynamic monitoring.