Organocatalytic Asymmetric Morita-Baylis-Hillman Reaction of Isatins with Vinyl Sulfones.

The organocatalytic asymmetric Morita-Baylis-Hillman (MBH) reaction of isatin derivatives with various vinyl sulfones is disclosed. Chiral sulfone-containing 3-hydroxyoxindoles were produced in good to high yields and with good to high ee's. This report displays an unprecedented example to apply activated alkenes with sulfone moiety other than carbonyl groups in asymmetric MBH reactions and provides an efficient strategy to incorporate the sulfone functional group for the synthesis of chiral 3-hydroxyoxindoles.

[Application of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the diagnosis and treatment of refractory pneumonia in children]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—æ¶²å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨å„¿ç«¥éš¾æ²»æ€§è‚ºç‚Žè¯Šæ²»ä¸­çš„åº”ç”¨.

OBJECTIVES: To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children. METHODS: A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment. RESULTS: Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment. CONCLUSIONS: Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.

RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.

AIM: Receptor-interacting protein 3 (RIP3) is involved in tumor necrosis factor receptor signaling, and results in NF-κB-mediated prosurvival signaling and programmed cell death. The aim of this study was to determine whether overexpression of the RIP3 gene could sensitize human breast cancer cells to parthenolide in vitro. METHODS: The expression of RIP3 mRNA in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435 and T47D) was detected using RT-PCR. Both MDA-MB-231 and MCF-7 cells were transfected with RIP3 expression or blank vectors via lentivirus. Cell viability was measured with MTT assay; intracellular ROS level and cell apoptosis were analyzed using flow cytometry. RESULTS: RIP3 mRNA expression was not detected in the four human breast cancer cell lines tested. However, the transfection induced higher levels of RIP3 protein in MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of RIP3 decreased the IC50 values of parthenolide from 17.6 to 12.6 µmol/L in MCF-7 cells, and from 16.6 to 9.9 µmol/L in MDA-MB-231 cells. Moreover, overexpression of RIP3 significantly increased parthenolide-induced apoptosis and ROS accumulation in MCF-7 and MDA-MB-231 cells. Pretreatment with N-acetyl-cysteine abrogated the increased sensitivity of RIP3-transfected MCF-7 and MDA-MB-231 cells to parthenolide. CONCLUSION: Overexpression of RIP3 sensitizes MCF-7 and MDA-MB-231 breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.

Effect of acupotomy combined with electroacupuncture on knee function of patients with knee osteoarthritis. / åˆƒé’ˆç»“åˆç”µé’ˆæ²»ç–—å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žæ‚£è€ è†å ³èŠ‚åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week；and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale ［WOMAC］) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.

Asymmetric total synthesis of caribenol A via an intramolecular Diels-Alder reaction.

A total synthesis of the caribenol A (1), a novel natural product with an intriguing tetracyclic framework, has been achieved. The synthesis features an intramolecular Diels-Alder (IMDA) reaction for the facile construction of the tricyclic [5-7-6] skeleton of caribenol A (1) and a biomimetic oxidation reaction for the formation of the 2-hydroxyfuran-2(5H)-one motif of caribenol A (1) as key steps. This synthetic approach also reveals that the sp(2) carbon at C(2) in substrate 8 is a critical factor for the formation of the tricyclic [5-7-6] skeleton in 7.

[Effect of jianpihuashi decoction on rats with hyperuricemia].

OBJECTIVE: To investigate the effect of Jianpihuashi Decoction on rats with hyperuricemia. METHODS: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups: normal, hyperuricemia, Jianpihuashi Decoction and Allopurinol group. After the administration for 0 day, 10 days, 20 days and 30 days, the serum uric acid, creatinine, urea nitrogen and xanthine oxidase (XOD) activity levels were separately detected using the orbital blood. 30 days after the experiment, the rats were anaesthetized by 3% pentobarbital sodium, liver tissue homogenate extracts were used to detect the XOD activity, and histopathological changes in kidney were observed by HE staining. RESULTS: Treatment with Jianpihuashi Decoction for 30 days, the serum uric acid level of rats with hyperuricemia were significantly decreased (P < 0.05). Simultaneously, the XOD activity in the serum and liver tissue homogenate extracts were obviously decreased by the decoction, which had seldom toxic or side effects on kidney. Allopurinol group could significantly decrease the serum uric acid level, but it had seldom pathological injury to kidney at the same time. CONCLUSION: Jianpihuashi Decoction which has seldom pathological injury to kidney can significantly decrease the effect of uric acid by suppressing XOD activity.

Eisenmenger syndrome: not always inoperable.

Recently, advanced therapies for pulmonary arterial hypertension have become available, and have been effective in reducing pulmonary vascular resistance and symptoms in patients with Eisenmenger syndrome, previously thought to be inoperable. This review summarizes the current knowledge on the pathophysiology and treatment of Eisenmenger syndrome. The recent introduction of targeted therapies in pulmonary arterial hypertension has led to a renewed insight in the pathophysiology and treatment of Eisenmenger syndrome. Patients with Eisenmenger syndrome using a diagnostic-treatment-and-repair strategy are amenable to surgery after successful treatment with advanced therapy. With continued improvements in the diagnosis, preoperative management, refinement of surgical techniques and intra- and postoperative management strategies, the patients with Eisenmenger syndrome selected using a diagnostic-treatment-and-repair strategy are operable with safety and efficacy in the current era with advanced pulmonary arterial hypertension therapy. Future directions of Eisenmenger syndrome may be the combination of reversal of pulmonary vascular remodeling and correction.

Inhibition of 11b-HSD1 by tetracyclic triterpenoids from Euphorbia kansui.

The roots of Euphorbia kansui are considered an important traditional folk medicine. In this study the ethanol extracts of E. kansui were investigated. A new tetracyclic triterpenoid, euphane-3b,20-dihydroxy-24-ene, in addition to five known triterpenoids with euphane skeletons were isolated. Their structures were elucidated on the basis of physical and spectral techniques (1D-, 2D-NMR and MS, respectively). Furthermore, these compounds 1-6 exhibited strong inhibitory activity against human 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), with IC(50) values of 34.86 nM, 1.115 mM, 16.08 nM, 2.815 nM, 26.47 nM, 15.99 nM, and 41.86 nM, respectively. The docking results show that the ring part of compounds can insert into the hydrophobic core of h11b-HSD1 and the alkane chain orientates toward the outside. The results presented herein provide a scientific explanation for the usage of the E. kansui in clinical treatment of diabetes.

Diastereo- and Enantioselective Synthesis of Borylated 3-Hydroxyoxindoles by Addition of gem-Diborylalkanes to Isatins.

The catalytic asymmetric synthesis of borylated 3-hydroxyoxindoles by addition of gem-diborylalkanes to isatins is disclosed. Chiral 3-hydroxyoxindoles bearing two contiguous stereogenic centers were produced in up to >20:1 dr and 99% ee. The synthetic utility of the corresponding products is presented through several transformations of the boryl moiety. This report provides an efficient strategy to incorporate a boryl functional group toward the synthesis of 3-hydroxyoxindoles.

[Efficacy and mechanism of electroacupuncture on insulin resistant polycystic ovary syndrome].

OBJECTIVE: To explore the therapeutic effect and partial mechanism of electroacupuncture (EA) for patients with insulin resistance (IR) polycystic ovary syndrome (PCOS). METHODS: Seventy patients with IR-PCOS were randomly divided into an EA group (36 cases, 5 cases dropped off) and a medication group (34 cases, 4 cases dropped off). The patients in the medication group were treated with oral administration of metformin hydrochloride, 500 mg each time, twice a day. The patients in the EA group were treated with EA (continuous wave, 2 Hz of frequency) at Zusanli (ST 36), Zhongwan (CV 12), Qihai (CV 6), Yishu (EX-B 3), Shenshu (BL 23), Pishu (BL 20), Ciliao (BL 32) for 30 min, three times a week. One menstrual cycle or 4 weeks were taken as a course of treatment, and 3 continuous courses were given. The follow-up was 3 months. The lipid metabolism indexes of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), homeostasis model assessment-insulin resistance index (HOMA-IR) and testosterone (T) in serum were compared before and after treatment, and the clinical effects of the two groups were evaluated during the follow-up. RESULTS: The total effective rate was 67.7% (21/31) in the EA group and 60.0% (18/30) in the medication group, with no significant difference between the two groups (P>0.05). After treatment, the levels of serum T, HOMA-IR, LDL, TG and TC were decreased significantly in the two groups (P<0.01, P<0.05), and HDL was increased significantly (P<0.01); the levels of TC in the EA group after treatment was lower than that in the medication group (P<0.05). CONCLUSION: EA may adjust some dyslipidemia in patients to correct IR and improve endocrine disorder of PCOS, which had superior/similar effects to metformin.

[An experimental study of bronchoscopic lung volume reduction medicine].

OBJECTIVE: To evaluate the effect and safety of experimental bronchoscopic lung volume reduction (BLVR) using an one-way valve designed independently. METHODS: The animal study was carried out from June to December 2008. Totally 36 valves were implanted in the target bronchi of 12 healthy male goats. CT scan, artery blood gas exchange and lung pathology were performed after 2, 4, 8 and 12 weeks. RESULTS: All the valves were implanted successfully, but 3 valves were expectorated at the end. The procedure was well tolerated. CT scan showed that for more than 45% (15/33) of the valves, the target lung tissue had collapsed. Lung pathology showed that the alveolar space was deflated and collapsed. Lymphocytes and monocytes infiltrated the interstitial tissue with some degree of fibrosis. CONCLUSIONS: This animal study showed that the independently manufactured one way valve was effective and safe. The one way valve may be useful in the treatment of severe emphysema in the future.

Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases through autophagy with low immunosuppressive effect.

Autophagy is an essential cellular process concern with cellular homeostasis down-regulated by mTOR, whose activity can be modulated by rapamycin, a kind of lipophilic macrolide antibiotic, through forming a complex with immunophilin FKBP12 essential for mTOR regulation to induce autophagy. Therefore, rapamycin is normally used as a neuron protective agent. The immunophilin FKBP12 binding ligand FK506 is well known as an immunosuppressive agent by inhibiting the calcineurin expression. In this study, we synthesized a series of modified compounds based on the FKBP12 binding moiety to as same as the binding structure of rapamycin and FK506 particularly. We removed the other binding regions of the complex that has the property of immunosuppression. We found that a novel small molecule named TH2849 from these derivative compounds has a significant binding connection with mTOR by comparing to calcineurin. The effects of TH2849 on calcineurin/NFAT were not as significant as FK506, and weak effects on IL2/p34cdc2 /cyclin signaling pathway were also found. Moreover, TH2849 also shows mitochondrial protective effect through stabilizing the mitochondrial structure and transmembrane potential (ΔΨm) and could rescue dopaminergic neurons in MPTP-treated zebrafishes as well as mice models with less immunosuppressive effect. Our present study shows that TH2849 works as a neuroprotective agent possibly by inducing autophagy and low immunosuppressive effect.

MicroRNA-129 and -335 Promote Diabetic Wound Healing by Inhibiting Sp1-Mediated MMP-9 Expression.

Diabetic wounds are recalcitrant to healing. However, the mechanism causing this dysfunction is not fully understood. High expression of matrix metalloproteinase-9 (MMP-9) is indicative of poor wound healing. In this study, we show that specificity protein-1 (Sp1), a regulator of MMP-9, binds directly to its promoter and enhances its expression. Additionally, we demonstrated that Sp1 is the direct target of two microRNAs (miRNAs), miR-129 and -335, which are significantly downregulated in diabetic skin tissues. In vitro experiments confirmed that miR-129 or -335 overexpression inhibits MMP-9 promoter activity and protein expression by targeting Sp1, whereas the inhibition of these miRNAs has the opposite effect. The beneficial role of miR-129 or miR-335 in diabetic wound healing was confirmed by the topical administration of miRNA agomirs in diabetic animals. This treatment downregulated Sp1-mediated MMP-9 expression, increased keratinocyte migration, and recovered skin thickness and collagen content. The combined treatment with miR-129 and miR-335 induced a synergistic effect on Sp1 repression and MMP-9 downregulation both in vitro and in vivo. This study demonstrates the regulatory mechanism of Sp1-mediated MMP-9 expression in diabetic wound healing and highlights the potential therapeutic benefits of miR-129 and -335 in delayed wound healing in diabetes.

[The quality control of carbonized cortex moutan].

OBJECTIVE: To set up method for the quality control of carbonized Cortex Moutan. METHODS: The optimized processing technology of carbonized Cortex Moutan was selected by the time of blood coagulation. Besides, the contents of tannin, adsorbability, paeonol and peoniflorin were researched. RESULTS: To parch the pieces 5 minutes at the temperature of 22 degrees C was the optimized processing technology. CONCLUSION: This study provides a reference to the institution for the quality standard of carbonized Cortex Moutan.

Potential role of pemetrexed in metastatic breast cancer patients pre-treated with anthracycline or taxane.

OBJECTIVES: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. METHODS: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ''pemetrexed'' or ''LY231514'' or "Alimta", "metastatic breast cancer", and "advanced breast cancer". RESULTS: There were 15 studies (n = 1002) meeting our criteria for evaluation. Eight single-agent trials (n = 551) and seven using combinations with other agents (n = 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. CONCLUSION: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists.

Ultrasonography guided percutaneous radiofrequency ablation for hepatic cavernous hemangioma.

AIM: Hepatic cavernous hemangioma (HCH) is the most common benign tumor of the liver and its management is still controversial. Recent success in situ radiofrequency ablation of hepatic malignancies has led us to consider using this technique in patients with HCH. This study was to assess the efficacy, safety, and complications of percutaneous radiofrequency ablation (PRFA) under ultrasonography guidance in patients with HCH. METHODS: Twelve patients (four men and eight women, age ranged 33-56 years, mean age was 41.7 years) with 15 hepatic cavernous hemangiomas (2.5 cm to 9.5 cm) were treated using the RF-2000 generator and 10-needle LeVeen electrode percutaneously guided by B-ultrasound. Lesions larger than 3 cm were treated by multiple overlapping ablations that encompass the entire lesion as well as a rim of normal liver tissue (approximately 0.5 cm). RESULTS: All the patients who received PRFA therapy had no severe pain, bleeding or bile leakage during and after the procedures. Nine to 34 months' follow-up (mean, 21 months) by ultrasound and/or spiral CT scan demonstrated that the ablated lesions in this group were shrunk remarkably, and the shrunken range was 38-79 % (mean, 67 % per 21 months). The contrast enhancement was disappeared within the tumor or at its periphery in all cases on spiral CT scans obtained 3 to 6 months after treatment. CONCLUSION: The results of this study suggest that PRFA therapy is a mini-invasive, simple, safe, and effective method for the treatment of selected patients with HCH.

Oxygen insertion of o-quinone under catalytic hydrogenation conditions.

An oxygen-insertion reaction that transforms an o-quinone and a conjugated α-diketone substrate into an anhydride product or derivative under catalytic hydrogenation conditions is reported. The experiments and computations indicate that the oxygen insertion proceeds via a radical mechanism mediated by an acetoxyl radical.

[Carbon exchange of Chinese boreal forest during its growth season and related regulation mechanisms].

Based on the two-year continuous observation on the carbon exchange of Chinese boreal forest during its growth seasons in 2007 and 2008 by the method of open path eddy covariance, this paper analyzed the seasonal dynamics of the gross ecosystem productivity (GEP), ecosystem respiration (Re), and net ecosystem carbon exchange (NEE) of the forest, with related regulation mechanisms approached. The GEP, Re, and NEE of the forest reached to their maximum in the vigorous growth period from late June to mid August, but the dates of the maximum appeared differed. The mean daily GEP, Re, and NEE were 19.45, 15.15, and -1.45 g CO2 x m(-2) x d(-1) in 2007, and 17.67, 14.11, and -1.37 g CO2 x m(-2) x d(-1) in 2008, respectively. The intensity of the carbon exchange during growth season was obviously stronger in 2007 than in 2008, possibly due to the higher mean air temperature (12.46 degrees C in 2007 vs. 11.04 degrees C in 2008) and the higher mean photosynthetically active radiation (PAR) (697 micromol x m(-2) x s(-1) in 2007 vs. 639 micromol x m(-2) x s(-1) in 2008). The GEP had close linear relationships with air temperature and PAR, and the correlation coefficient of GEP and air temperature was around 0.55 (P<0.01). The Re was mainly controlled by air temperature, with the correlation coefficient being 0.66-0.72 (P<0.01), and the NEE was mainly controlled by PAR, with the correlation coefficient being 0.59-0.63 (P<0.01).

[In situ measurement of atmospheric HCFC-22 at the Shangdianzi GAW regional station].

An in situ GC-ECD monitoring system was established at the Shangdianzi GAW Regional station from April 2007 to March 2008, and the mixing ratio of atmospheric HCFC-22 was (278.1 +/- 113.6) x 10(-12) (mol/mol). A "R" statistical software was applied to the HCFC-22 time series to separate background and pollution data. The background HCFC-22 mixing ratio was (199.5 +/- 5.1) x 10(-12), close to northern hemisphere background level observed at Mace Head and Trinidad Head stations. The pollution HCFC-22 mixing ratio was (312.1 +/- 121.0) x 10(-12) due to anthropogenic emission from various regions and air mass transport. There was no significant seasonal variability of background data. However, pollution data was much higher in summer than that in winter, and elevated up to 100.9 x 10(-12) in July than in January attribute to seasonal emission characteristics. The mean HCFC-22 mixing ratio from southwest wind sector (327.3 x 10(-12)) was much higher than that of northeast sector (236.2 x 10(-12)). The W-WSW-SW wind sector has a positive contribution to the HCFC-22 level, while NNE-N-NE has a large negative contribution.