Construction of cyclobutane-fused tetracyclic skeletons via substrate-dependent EnT-enabled dearomative [2+2] cycloaddition of benzofurans (benzothiophenes)/maleimides.

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons.

Photomediated Hydro(deutero)acylation of Olefins by Decarboxylative Addition of α-Oxocarboxylic Acids.

Acyl radicals have been generated from the decarboxylation of α-oxocarboxylic acids by using a readily accessible organic pyrimidopteridine photoredox catalyst under ultraviolet-A (UV-A) light irradiation. These reactive acyl radicals were smoothly added to olefins such as styrenes and diverse Michael acceptors, with the assistance of H2O/D2O as hydrogen donors, enabling easy access to a diverse range of ketones/ß-deuterio ketones. A wide range of α-oxocarboxylic acids are compatible with this reaction, which shows a reliable, atom-economical, and eco-friendly protocol. Furthermore, postsynthetic diversifications and applications are presented.

[Effect of moxibustion combined with acupoint catgut embedding on IL-6/JAK/STAT3 signaling pathway in colonic mucosa of ulcerative colitis rats].

OBJECTIVE: To observe the effect of moxibustion combined with acupoint catgut embedding on the content of interleukin 6 (IL-6), and the expressions of janus activated kinase (JAK), signal transducer and activator of transcription 3 (STAT3) in colonic mucosa of rats with ulcerative colitis (UC), so as to explore its mechanism underlying improvement of UC. METHODS: Thirty SD rats were randomly divided into normal, model, acupoint catgut embedding (ACE), moxibustion and acupoint catgut embedding combined with moxibustion (combination) groups (n=6 rats in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral "Tianshu" (ST25), "Dachangshu" (BL25) and "Shangjuxu" (ST37) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed by H.E. staining, the level of IL-6 in colonic mucosa was assayed by ELISA, and the expressions of JAK and STAT3 in colonic mucosa were detected by immunohistochemistry and Western blot. RESULTS: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and combination groups. After modeling, the content of colonic IL-6, and the expression levels of JAK and STAT3 were obviously increased (P<0.01) in the model group relevant to the normal group. Following the intervention, the increase of IL-6 contents, and JAK and STAT3 expressions were reversed (P<0.05, P<0.01) in moxibustion, ACE and combination groups. The therapeutic effects of moxibustion combined with ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of JAK and STAT3 expression (P<0.01). CONCLUSION: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effect in suppressing the activation of IL-6/JAK/STAT3 signaling pathway.

[Effect of Astragali Radix-Curcumae Rhizoma compatibility combined with 5-fluorouracil on Th17/Treg balance and tumor-related mRNA and protein expression in orthotopic xenograft model mice of CT26.WT colorectal carcinoma].

Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-ß(TGF-ß), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-ß, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-ß, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

[Effect of acupoint catgut embedding combined with moxibustion on Notch signaling pathway in colonic mucosa of rats with active ulcerative colitis].

OBJECTIVE: To observe the effect of acupoint catgut embedding (ACE) combined with moxibustion on the expressions of Notch receptor 1 and target genes Hes 1 and Math 1 in colonic mucosa of ulcerative colitis (UC) rats, so as to reveal its mechanism of treating UC from the perspective of Notch signaling pathway. METHODS: Thirty SD rats were randomized into normal, model, ACE combined with moxibustion (combination), ACE, and moxibustion groups (n=6 in each group). The UC model was established by intrarectal administration of 5% trinitro-benzene-sulfonic acid and 50% ethyl alcohol. Moxibustion was applied to bilateral "Shangjuxu" (ST37), "Tianshu" (ST25) and "Dachangshu" (BL25) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed after hematoxylin eosin (HE) stain. Protein and mRNA expressions of Notch 1, Hes 1 and Math 1 were detected by RT-PCR and Western blot, respectively. RESULTS: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and moxibustion + ACE groups. After modeling, the protein and mRNA expressions of Notch 1 and Hes 1 in the colonic mucosa were obviously increased (P<0.01), while the protein and mRNA expressions of Math 1 were significantly decreased (P<0.01) in the model group relevant to the normal group. Following the intervention, the protein and mRNA expression levels of Notch 1 and Hes 1 in the colonic mucosa were significantly lower (P<0.05, P<0.01) in moxibustion, ACE and combination groups, the mRNA expression level of Math 1 was significantly increased in both ACE and combination groups (P<0.01), and the protein expression of Math 1 was significantly higher in the three treatment groups relevant to the model group (P<0.01). The above indexes of moxibustion + ACE were considerably superior to those of simple ACE and simple moxibustion (P<0.05, P<0.01). CONCLUSION: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effects in suppressing the expression of Notch 1 and Hes 1, up-regulating the expression of Math 1 in the colonic mucosa, thereby regulating the balance of differentiation between colonic epithelial secretory and absorption cell lines.

[Moxibustion combined with acupoint catgut embedding promotes recovery of injured colonic mucosa by suppressing inflammation in ulcerative colitis rats].

OBJECTIVE: To observe the effect of moxibustion and acupoint catgut embedding (ACE) at "Tianshu"(ST25) "Dachangshu"(BL25) and "Shangjuxu"(ST37) on changes of body mass, stool property, histopathological conditions and expression levels of interleukin 6 (IL-6) in colonic mucosa of ulcerative colitis (UC) rats, so as to reveal its anti-inflammatory mechanisms underlying improvement of UC. METHODS: SD rats were randomized into normal, model, moxibustion, ACE and moxibustion＋ACE groups (n＝6 in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral ST25, BL25 and ST37 for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, the rats' general conditions were observed, and the severity of UC was assessed by using disease activity index (DAI) score. Colonic mucosal pathological changes were observed under microscope after hematoxylin eosin (H.E.) stain, and the expression levels of IL-6 in the colonic mucosa tissue detected by using immunohistochemical stain and Western blot, respectively. RESULTS: After modeling, the DAI score, and expression level of colonic IL-6 protein detected by immunohistochemistry and Western blot were obviously increased in the model group relevant to the normal group (P<0.01). Following the intervention, the increase of DAI score and IL-6 expression were reversed in moxibustion, ACE and moxibustion＋ACE groups (P<0.01, P<0.05). The therapeutic effects of moxibustion＋ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of DAI score and IL-6 expression (P<0.01). H．E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and moxibustion＋ACE groups. CONCLUSION: Moxibustion combined with ACE is able to improve the inflammatory injury of colonic mucosa in UC rats, which may be related with its effect in suppressing the expression of colonic IL-6; and the efficacy of moxibustion＋ACE is apparently superior to that of moxibustion and ACE alone.

Changing patient safety culture in China: a case study of an experimental Chinese hospital from a comparative perspective.

BACKGROUND: The World Health Organization highlights that patient safety interventions are not lacking but that the local context affects their successful implementation. Increasing attention is being paid to patient safety in Mainland China, yet few studies focus on patient safety in organizations with mixed cultures. This paper evaluates the current patient safety culture in an experimental Chinese hospital with a Hong Kong hospital management culture, and it aims to explore the application of Hong Kong's patient safety strategies in the context of Mainland China. METHODS: A quantitative survey of 307 hospital staff members was conducted using the Hospital Survey on Patient Safety Culture questionnaire. The findings were compared with a similar study on general Chinese hospitals and were appraised with reference to the Manchester Patient Safety Framework. RESULTS: Lower scores were observed among participants with the following characteristics: males, doctors, those with more work experience, those with higher education, and those from the general practice and otolaryngology departments. However, the case study hospital achieved better scores in management expectations, actions and support for patient safety, incident reporting and communication, and teamwork within units. Its weaknesses were related to non-punitive responses to errors, teamwork across units, and staffing. CONCLUSIONS: The case study hospital contributes to a changing patient safety culture in Mainland China, yet its patient safety culture remains mostly bureaucratic. Further efforts could be made to deepen the staff's patient safety culture mind-set, to realize a "bottom-up" approach to cultural change, to build up a comprehensive and integrated incident management system, and to improve team building and staffing for patient safety.