The prevalence and associated factors of metabolic syndrome among Tibetan pastoralists in transition from nomadic to settled urban environment / 中华流行病学杂志

Objective: To study the prevalence and associated factors of metabolic syndrome (MS) among Tibetan pastoralists in transition from high altitude nomadic to settled urbanized environment, especially dietary factors. Methods: The community-based cross-sectional study included 920 Tibetan adults (men 419, women 501). Data were collected using questionnaires, anthropometric measurements, and biomarker tests. Questionnaires included socio-economic, lifestyle characteristics and food consumption. Principal component analysis was used to identify dietary patterns. The risk factors of MS and its components were analyzed by logistic regression model. Results: The prevalence rates of MS and its components were 32.8% (MS), 83.7% (decreased HDL-C), 62.1% (central obesity), 36.7% (elevated blood pressure), 11.8% (elevated TG), and 7.9% (elevated blood glucose), respectively. The prevalence of overweight was 31.2%, obesity 30.3%. Multivariate analysis showed smoking was associated factor for both of decreased HDL-C (OR=1.239, 95%CI: 1.025-1.496) and elevated TG (OR=1.277, 95%CI: 1.038-1.571). Alcohol drinking appeared as associated factor of elevated TG (OR=1.426, 95%CI: 1.055-1.927). However, physical activity showed as a protective factor for central obesity, decreased HDL-C, and elevated TG. With the increase of age, the adherence to the urban and western dietary patterns decreased, and that to the pastoral dietary pattern increased. By quintiles of dietary pattern scores, the urban dietary pattern was significantly associated with MS (trend test P=0.016). Conclusions: Tibetan pastoralists had high prevalence of both MS and obesity. Smoking, alcohol drinking, the transition from pastoral dietary pattern to urban dietary pattern and inadequate physical activity served as associated factors for MS and its components.

Synthesis and evaluation on triglyceride inhibitory activities of novel indole alkaloids / 药学学报

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC50 value of 6.35 μmol·L-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

Advances in small molecular inhibitors of IL-6/STAT3 signaling pathway / 药学学报

As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.

Effect of ligustilide on oxygen and glucose deprivation/reperfusion-induced mitochondria fission in PC12 cells / 中国中药杂志

This study aimed to investigate the effect and mechanism of ligustilide, the main active ingredient in Ligusticum wallichii, on mitochondria fission after PC12 cell injury induced by oxygen and glucose deprivation/reperfusion(OGD/R). In the experiment, an OGD/R model was established in vitro, and PC12 cells were pre-treated with ligustilide for 3 h, and then the cell viability was detected by CCK-8 method. The effect of different concentrations of ligustilide on the morphology of PC12 cells after OGD/R injury was observed under an inverted microscope. Transmission electron microscopy was used to observe the mitochondrial fission of PC12 cells after OGD/R injury. DCFH-DA immunofluorescence staining method was used to detect intracellular reactive oxygen species(ROS) changes. Changes in mitochondria membrane potential(MMP) were detected by flow cytometry. Hochest 33258 was used to observe the apoptosis of PC12 cells. Western blot was used to detect changes in cytochrome C(Cyt C) content in mitochondria and cytoplasm, and mitochondrial fission-related proteins Drp 1 and Fis 1. All results showed that compared with the model group, ligustilide significantly increased the survival rate of PC12 cells and the number of cells. Further experiments showed that ligustilide inhibited the release of ROS and decline of mitochondrial membrane potential in PC12 cells after OGD/R injury. Moreover, ligustilide reduced the release of Cyt C and promoted the expressions of Drp1 and Fis1 in mitochondrial fission proteins. Verification experiments showed that mitochondrial fission inhibitor mdivi-1 decreased cell survival rate and inhibited fission. The results indicated that ligustilide exerted neuro-protective effects by promoting mitochondrial fission and reducing cell damage. It preliminary proves that the mechanism of ligustilide on ischemic brain injury may be related to the promotion of mitochondrial fission and the maintenance of cell homeostasis.

Anti-MRSA activities of cycloberberine derivatives with a novel chemical scaffold / 药学学报

Using CBBR as the parent core constructed in our lab, we designed and synthesized 15 novel compounds with diverse structures for evaluation of anti-bacterial activities. Structure activity relationship studies revealed that ① ring C was essential for the activity; ② 7,8- or 8,13-disubstituted CBBR derivatives showed ideal activities, weaker or similar to those corresponding to 7-, 8-, or 13-monosubstituted CBBR derivatives. Among those, compound 9a showed the most potential activity against MRSA/VISA isolates with MIC values of 1-2 μg·mL-1, much better than Lev. 9a also displayed higher stability in the plasma and liver microsomes. Molecular docking indicated that 9a might target bacterial DNA Topo IV ParE subunit, indicating a mode of action distinct from current antibacterial drugs on market. The results provided key scientific evidence for developing such compounds into a new family of anti-MRSA drugs.

Design, synthesis and anti-MRSA activities of cycloberberine derivatives with a novel chemical scaffold / 药学学报

9-Acetoxycycloberberine (1) with a unique skeleton was first identified to display a potent antimicrobial profile against methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 1-16 μg·mL-1. Taking the compound as a lead, 14 target cycloberberine analogues with diverse structures, such as berberine and chelerythrine derivatives, were synthesized and evaluated for their anti-bacterial activities. Analysis of the structure-activity relationship revealed that:① ring E was essential for the activity; ② the removing of ring B decreased the activity against MRSA. However, the antimicrobial activity against vancomycin-resistant Enterococcus faecium (VRE) was improved; ③ the introduction of a suitable rigid substituent at the 9-position was beneficial for the activity. Among them, compound 9a showed the most potential activity against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA isolates with MIC values of 0.5-1 μg·mL-1, suggesting a different mechanism from clinical drugs. It displayed higher stability in blood. Therefore, we consider 9a worthy of further investigation. The results provide key scientific evidence for development of such compounds into a new type of anti-MRSA candidates.

Design, synthesis and evaluation of anti-inflammatory effect of novel berberine derivatives on IL-6/STAT signaling pathway / 药学学报

Interleukin-6 (IL-6)/signal transducers and activators of transcription (STAT) signaling pathway is closely related to the development and progression of atherosclerosis (AS). Taking Chinese natural product berberine (BBR) as the leading compound, a series of novel BBR analogues defined on different types of substituents on position 3 or/and 9 were designed, synthesized and evaluated for their inhibitory activities on phosphorylation of STAT-1 and STAT-3 induced by IL-6. The structure-activity relationship indicated that introduction of rigid fragment on position 3 or 9 was beneficial for enhancing their activities. Among them, compounds 2b and 9 exhibited the most satisfactory potency. The study revealed that the compounds 2b and 9 exhibit anti-inflammatory potencies via activating AMPK, and down-regulation of phosphorylation of STAT1 and STAT3 induced by IL-6 in HUVEC cells. These results suggest that BBR derivatives may inhibit the inflammatory response mediated by the IL-6/STAT signaling pathway through regulation of AMPK, which provides useful insight into the development of BBR derivatives for treatment of atherosclerosis.

Treatment of comminuted fracture of tibial plateau with ni-ti shape memory alloy bow-teeth screws combined with locking plate internal fixation / 中国骨伤

<p><b>OBJECTIVE</b>To assess the clinical effects of Ni-Ti shape memory alloy bow-teeth screws combined with locking plate internal fixation in treating comminuted fracture of tibial plateau.</p><p><b>METHODS</b>From January 2003 to December 2008, 17 patients with comminuted fracture of tibial plateau were treated with Ni-Ti shape memory alloy bow-teeth screws and locking plate internal fixation. There were 9 males and 8 females with an average age of 33.7 years old (ranged, 23 to 48 years). All fractures were fresh and injured time less 3 weeks and 2 patients with common peroneal nerve injury. According to Schatzker typing, type V was in 1 case and type VI was in 16 cases.</p><p><b>RESULTS</b>All patients were followed up from 10 to 22 months with an average of 18 months and all incisions healed in one stage. At 3 to 12 weeks after operation, knee joint function of 16 cases arrived to the level of uninjured side and 1 case was poor in flexed function. All fractures obtained union at 3 to 5 months after operation, and internal fixtures were removed at 1 year after operation and no reduction lossing or refracture occurred. At final follow-up, no bone block shifting, internal fixture loosening and breakage was found. According to the standard of Xushanding's knee joint function, 9 cases got excellent results, 4 good, 4 fair.</p><p><b>CONCLUSION</b>The design of Ni-Ti shape memory alloy bow-teeth screws is adapt to irregular anatomic structure of comminuted fractures of tibial plateau,it can continuously pressurize and promote bone healing. Multi drop lockedup may avoid wide-ranging stripping local soft tissue, and form three-dimension fixation after combined with locking plate internal fixation, can effective recover anatomic structure of fracture. So Ni-Ti shape memory alloy bow-teeth screws combined with locking plate internal fixation is an effective method in treating comminuted fracture of tibial plateau.</p>

Synthesis and structure-activity relationship of N-(2-arylethyl) isoquinoline derivatives as anti-cancer agents / 药学学报

A series of novel N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their anti-cancer activities. Among these analogs, compound 9a exhibited the potential anti-cancer activities on HepG2 and HCT116 cells with IC50 values of 2.52 and 1.99 microg x mL(-1), respectively. Cell cycle was blocked at S phase of HepG2 cells treated with 9a by flow cytometry detection. Our results provided a basis for the development of a new series of anti-cancer candidates.

Observation on therapeutic effects of acupuncture combined with TDP irradiation and chinese herbal steaming and washing therapy for treatment of carpal tunnel syndrome in early stage / 中国针灸

<p><b>OBJECTIVE</b>To search for an effective therapy for carpal tunnel syndrome in early stage.</p><p><b>METHODS</b>Sixty cases were randomly divided into an observation group 1 (21 cases), an observation group 2 (22 cases) and a basic treatment group (17 cases). The patients in three groups were treated with oral administration of Vitamin B1, Vitamin B12, compound Vitamin B and small splint for wrist protection as basic treatment, and the observation group 1 was also treated with acupuncture on local points as Laogong (PC 8), Yuji (LU 10), Hegu (LI 4) and Waiguan (TE 5) etc. combined with TDP irradiation, and the observation group 2 was treated with herbal steaming and washing on the affected part using Safflower and Lopseed etc. Electromyography, visual analogue scale (VAS) and clinical effect of three groups were observed before and after treatment.</p><p><b>RESULTS</b>The changes of electromyogra phy had no significant difference before and after treatment in all groups (all P > 0.05), the VAS scores in two ob servation groups were superior to that in basic treatment group (both P < 0.05). The excellent and good rates were 90.5% and 86.4% in the observation group 1 and the observation group 2 respectively, both higher than that of 64.7% in the basic treatment group.</p><p><b>CONCLUSION</b>Acupunture combined with TDP irradiation and Chinese herbal steaming and washing therapy both have significant therapeutic effects for treatment of carpal tunnel syndrome in early stage.</p>

Epidemic survey on TCM syndrome typing and preliminary discussion on TCM etiology and pathogenesis of fatty liver / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the common TCM syndrome types of fatty liver by way of epidemic questionnaire, their occurrence ratio, and the correlation between various syndrome types and objective indexes.</p><p><b>METHODS</b>A total of national wide 503 subjects with fatty liver were enrolled, the TCM syndromes, body mass index (BMI), abdominal perimeter/hip circumference, liver function, blood lipids, B ultrasonic examination and CT in them were observed and recorded.</p><p><b>RESULTS</b>In the 46 symptoms investigated in total, the first ten symptoms in order of appearing rate were lassitude, obese, oral dryness, vertigo, hypochondriac distending pain, soreness and pain in loin, spiritlessness, oral bitterness, aching and weakness in knee and abdominal distention. The mostly appeared tongue figures were pale and corpulent or pale dim tongue proper, white greasy or yellow greasy tongue coating, and the mostly appeared pulse figures were taut, taut-thin and taut slippery. Statistical cluster analysis showed that syndromes of fatty liver could be typed into 4 TCM types, the asthenia Pi-Shen with Gan-stagnation type, the asthenia Pi-Shen type, the asthenia Pi with phlegm-heat type and the unclassified type. Among them the asthenia Pi-Shen with Gan-stagnation type was the commonest one, which accounted to 62.32%.</p><p><b>CONCLUSION</b>The mostly appeared syndrome type of fatty liver was asthenia Pi-Shen with Gan-stagnation type. The TCM pathogenesis of fatty liver was deficiency of origin, mainly deficiency of Shen, involving Pi, with excess superficiality, the turbid-phlegm and blood stasis.</p>