Increased Dietary Niacin Intake Improves Muscle Strength, Quality, and Glucose Homeostasis in Adults over 40 Years of Age.

BACKGROUND AND AIMS: Age-related loss of skeletal muscle mass and strength begins at 40 years of age, and limited evidence suggests that niacin supplementation increases levels of nicotinamide adenine dinucleotide in mouse muscle tissue. In addition, skeletal muscle has a key role in the body's processing of glucose. Therefore, this study aimed to investigate the relationship between dietary niacin and skeletal muscle mass, strength, and glucose homeostasis in people aged 40 years and older. METHODS: This study was an American population-based cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES). Considering that some outcomes are only measured in specific survey cycles and subsamples, we established three data sets: a grip strength dataset (2011-2014, n=3772), a body mass components dataset (2011-2018, n=3279), and a glucose homeostasis dataset (1999-2018, n=9189). Dietary niacin and covariates were measured in all survey cycles. Linear regression or logistic regression models that adjusted for several main covariates, such as physical activity and diet, was used to evaluate the relationship between dietary niacin and grip strength, total lean mass, appendicular lean mass, total fat, trunk fat, total bone mineral content, homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glycose, fasting insulin and sarcopenia risk. Subgroup analyses, a trend test, an interaction test, and a restricted cubic spline were used for further exploration. RESULTS: Higher dietary niacin intake was significantly correlated with higher grip strength (ß 0.275, 95% confidence intervals [CI] 0.192-0.357), higher total lean mass (ß 0.060, 95% CI 0.045-0.074), higher appendicular lean mass (ß 0.025, 95% CI 0.018-0.033), and higher total bone mineral content (ß 0.005, 95% CI 0.004-0.007). By contrast, higher dietary niacin intake was significantly associated with lower total fat (ß -0.061, 95% CI -0.076 to -0.046), lower trunk fat (ß -0.041, 95% CI -0.050 to -0.032) and lower sarcopenia risk (OR 0.460, 95% CI 0.233 to 0.907). In addition, dietary niacin significantly reduced HOMA-IR, fasting blood glucose (in participants without diabetes), and fasting insulin (p <0.05). CONCLUSION: Niacin is associated with improved body composition (characterized by increased muscle mass and decreased fat content) and improved glucose homeostasis in dietary doses. Dietary niacin supplementation is a feasible way to alleviate age-related muscular loss.

[Clinical study of digital six-axis external fixation frame based on CT data for tibiofibular fractures].

Objective: To investigate the clinical effect of applying the digital six-axis external fixation frame based on CT data in the treatment of tibiofibular fractures. Methods: The clinical data of 43 patients with tibiofibular fractures treated by the self-developed digital six-axis external fixation frame based on CT data at Integrated Orthopedic Department of Traditional Chinese Medicine (TCM) and Western Medicine,HongHui Hospital from January 2018 to January 2021 were retrospective analysis.There were 27 males and 16 females,aged (36.0±9.4) years(range:25 to 50 years).AO classification:15 cases of 42A,11 cases of 42B, and 17 cases of 42C.There were 7 open fractures and Gustilo fracture classification:2 cases of type Ⅰ,4 cases of type Ⅱ,and 1 case of type Ⅲ.The two or three plane rings were connected with six connecting rods to form a complete six-axis external fixation frame,and the distal and proximal fracture blocks were connected to the distal and proximal rings by fixation pins,and the lengths of the six connecting rods needed to be adjusted were calculated by using the supporting software according to the CT data after surgery,and then the lengths of the connecting rods were adjusted one by one to complete the reduction of the fracture. The reduction accuracy of this six-axis external fixation brace was evaluated by measuring postoperative radiographs; postoperative recovery and complications were collected,the time of brace removal was recorded,and the function of the affected limb was evaluated according to the Johner-Wruhs score at the final follow-up. Results: Postoperative radiographs showed that all patients achieved satisfactory reduction with lateral displacement(M(IQR)) of 2.3(2.5) mm (range:0.3 to 7.3 mm),anteroposterior displacement of 2.1 (2.4) mm (range:0.3 to 5.7 mm),anteroposterior angulation of 2.5(2.4)°(range:0 to 5°),internal and external angulation of 2.1(1.5)°(range:0 to 4°), and no significant internal or external rotational deformity was detected on the exterior.On the second postoperative day,all patients were able to walk with partial weight-bearing on crutches. All 43 patients were followed up for more than 6 months,with a follow-up period of (33.3±7.3) weeks (range:24 to 42 weeks).The external fixation frame was removed after the fracture healed.The external frame was removed at 20(3)weeks (range:18 to 25 weeks) postoperatively. Up to the final follow up, no secondary fracture occurred in any of them.The Johner-Wruhs score of the affected limb at the last follow-up was excellent in 39 cases and good in 4 cases. Conclusion: The digital six-axis external fixator based on CT data for tibiofibular fractures has the advantages of precise reduction,firm fixation,simple operation,rapid fracture healing,and minimal trauma, which is a minimally invasive method for treating tibiofibular fractures,especially suitable for patients with poor skin and soft tissue conditions such as open injuries.

Coffee consumption and its interaction with the genetic variant AhR rs2066853 in colorectal cancer risk: a case-control study in Korea.

The bioactive compounds in coffee have several antioxidant properties that may beneficially impact colorectal cancer (CRC) development. The aryl hydrocarbon receptor (AhR) is an important transcription factor that regulates an enzyme related to the caffeine metabolism pathway. We investigated the modification effect on coffee of AhR gene polymorphism in the risk of CRC. A case-control study was conducted with 699 cases and 1393 controls to investigate the interaction between coffee intake and the AhR rs2066853 variant in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using multiple logistic regression analyses. We observed a significant protective effect of coffee against CRC in the overall and male populations. Consuming three or more cups of coffee per day may significantly lower CRC risk in all subjects by 77% and in men by 83% (OR = 0.23, 95% CI: 0.14-0.39 and OR = 0.17, 95% CI: 0.09-0.34, respectively, P-trends < 0.001). No association between AhR rs2066853 and CRC risk was found. In the dominant model, the G/G genotype had a strongest synergistic effect with coffee on protection against CRC (OR = 0.12, 95% CI: 0.06-0.26, P-interaction = 0.014). The interaction remained significant in men and the distal colon cancer subgroup. In the additive model, the interaction was clearly shown strongest in G/G carriers (OR = 0.12, 95% CI: 0.06-0.27, P-interaction = 0.039), followed by A/A and G/A carriers. The interaction remained significant in men and the rectal cancer subgroup. In conclusion, the protective effect of coffee on CRC risk might interact with the genetic variant AhR rs2066853, and this joint effect was determined by sex and site-specific cancer.

Traditional Chinese medicine reverses cancer multidrug resistance and its mechanism.

Chemotherapy is one of the most commonly used clinical treatments among the currently available cancer therapies. However, the phenomenon of Multidrug resistance (MDR) has become a challenge in the treatment process, weakening the impact of chemotherapy. Extensive research on elucidating the development of cancer MDR has identified the following mechanisms that play a critical role in the development of several MDR reversal agents: abnormal expression of cell membrane transporters, adaptation of cancer cells to the microenvironment, regulation of hypoxia, repair of DNA damage and reduction of apoptosis, the enhancement of the EMT process, the existence of cancer stem cells (CSCs), and the abnormal activation of key signaling pathways. However, they failed to demonstrate significant efficacy due to severe side effects during their clinical trials. Traditional Chinese medicines (TCMs) are known to play an important anti-cancer role since they have low toxicity, high efficacy, and safety and can reverse MDR. TCMs reversal agents can be divided into Chinese medicine monomers, synthetic monomers, analogs, or derivatives. Several studies have shown that TCMs can effectively overcome cancer MDR and can be effectively used for treating cancer patients.

The effects of gastric cancer interstitial fluid on tumors based on traditional Chinese medicine 'phlegm' theory and the investigation on the mechanism through microRNA-21 regulation.

This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues.

[A case of decompression sickness complicated with multiple organ failure treated by hyperbaric oxygen therapy sequential with continuous renal replacement therapy and extracorporeal membrane oxygenation].

Objective: To discuss the new idea of on-the-spot recompression treatment and multidisciplinary treatment (MDT) for patients with unstable vital signs of type II decompression sickness. To provide reference for the nearby treatment of patients with critical decompression sickness. Methods: The clinical data of a case of a multi-disciplinary collaborative treatment of type II decompression sickness complicated with multiple organ dysfunction syndrome (MODS) admitted to a third-class A hospital in January 2020 were analyzed and summarized. Results: The patient suffered from consciousness disturbance and shock after 3 min of diver's blow-up out of the water. CT examination showed gas accumulation in the systemic multi-organ venous system, and laboratory examination suggested MODS. The oxygen inhalation regimen was given in the session of recompression treatmen by 0.12-0.18 MPa. Intravenous fluid was the total of 8900 ml in the session, and the total recompression treatment time was 9 h 45 min. The patient was still in unconscious when he finished the session. CT re-examination confirmed the elimination of venous bubbles, and laboratory examination indicated multiple organ failure (MOF) . The patient was given comprehensive supporting treatment by mechanical assisted breathing and following by continuons renal replacement therapy (CRRT) and extrocorporeal membrane oxygenation (ECMO) in the intensive care unit, and was discharged after 32 d of hospitalization. Conclusion: Critical decompression sickness patients with unstable vital signs are taken to a local general hospital with hyperbaric oxygen chamber and intensive care unit. The successful treatment can be achieved by organizing diving medicine, hyperbaric oxygen medicine and critical medical personnel for MDT.

Systematic review and meta-analysis of refractometry for diagnosis of inadequate transfer of passive immunity in dairy calves: Quantifying how accuracy varies with threshold using a Bayesian approach.

Inadequate transfer of passive immunity (TPI) is associated with increased risk for calfhood disease and increased risk of mortality and morbidity. Accurately diagnosing calves and herds with inadequate TPI is of primary importance and brix (BRIX) or classical refractometer (REF) devices are more practical for this purpose than measuring the serum immunoglobulin G concentration in neonatal calves. We previously reported a systematic review and meta-analysis for quantifying the pooled accuracy of BRIX and REF for detecting calves with serum IgG < 10 g/L noting that sparse data were available especially because studies did not report the same thresholds. We updated the previous systematic review using different methods that accounted for the test results distribution in calves with or without inadequate TPI. With this approach, all reported cut-offs for a specific study are used in that Bayesian approach that quantifies how accuracy varied among all reported thresholds. Five new manuscripts were included, which represented 4 new studies since the initial study was performed. A total of 11 REF and 9 BRIX studies were available. The meta-analytic methods allowed reporting variation of the true and false positive rate across and among all reported cut-offs. Pooled points estimates (95 % Bayesian credible intervals) for sensitivity (Se) and specificity (Sp) of REF < 5.5 g/L were 86.1 % (68.5-97.9%) and 76.2 % (65.9-88.4%) whereas BRIX < 8.4 % was associated with Se of 91.6 % (77.2-99.5%) and Sp of 88.2 % (65.4-99.8%). Interestingly, the accuracy (Se + Sp-1) was generally higher for BRIX than for REF at the reported cut-offs. Besides the benefit of providing pooled estimates for all reported and unreported BRIX and REF thresholds, the general framework used in this study could potentially be used in many veterinary diagnostic tests studies that reported multiple thresholds accounting for potentially different tests distributions in population with and without the target condition.

Effects of non-drug interventions on depression, anxiety and sleep in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVE: Patients with Coronavirus Disease 2019 (COVID-19) suffer from anxiety, depression and sleep disorders due to isolation treatment, among other reasons. Whether non-drug interventions can be alternative therapies for COVID-19 patients with anxiety, depression and sleep disorders is controversial. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of non-drug interventions on anxiety, depression and sleep in patients with COVID-19 to provide guidance for clinical application. MATERIALS AND METHODS: We searched the following databases for randomized controlled trials (RCTs) from December 2019 to July 2020: China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Wanfang, Cochrane Library, Web of Science, PubMed, MEDLINE and Embase. Two investigators independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 5 articles with 768 subjects were included. Meta-analysis results indicated that non-drug interventions can reduce anxiety [SMD=-1.40, 95% CI (-1.62, -1.17), p<0.00001] and depression [SMD=-1.22, 95% CI (-2.01, -0.43), p=0.002] scores in patients with COVID-19. Descriptive analysis indicated that non-drug interventions can improve the sleep status of COVID-19 patients. Sensitivity analysis indicated that the meta-analysis results were stable. Egger's test and Begg's test showed no publication bias. CONCLUSIONS: This meta-analysis found that non-drug interventions can reduce the anxiety and depression scores of patients with COVID-19. Due to the limitations of this study, more high-quality studies are needed to verify the findings, especially the effect of non-drug interventions on improving the sleep status of COVID-19 patients.

Specific PCR-based detection of Phomopsis heveicola the cause of leaf blight of Coffee (Coffea arabica L.) in China.

Coffee (Coffea arabica L.) is currently grown in many tropical and subtropical areas countries and is a major traded commodity for the developing world. Coffee leaf blight, caused by Phomopsis heveicola, is one of the most important fungal diseases dangerous to coffee crops in China. This study aimed to develop a PCR-based diagnostic method for detecting P. heveicola in planta. Specific primers (CPHF/CPHR) were designed based on sequence data of region of internal transcribed spacer (ITS1 and ITS4) of P. heveicola. The efficiency and specificity of CPHF/CPHR were established by PCR analysis of DNA from P. heveicola strains isolated from China and fungal isolates of other genera. A single amplification product of 318 bp was detected from DNA P. heveicola isolates. No amplification product was observed with any of the other fungal isolates tested. The specific primers designed and employed in PCR detected P. heveicola up to 3 pg from DNA isolated. This is the first report on the development of a species-specific PCR assay for identification and detection of P. heveicola. Thus, the PCR-based assay developed was very specific, rapid and sensitive tool for the detection of pathogen P. heveicola.

[Treatment of Chilomastix mesnili infection with traditional Chinese medicine: a case report].

This paper reports a case with Chilomastix mesnili infections, and summarizes the diagnosis and treatment with traditional Chinese medicine.

[The status analysis of diagnosis and treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China: a report of 1 003 cases in 16 domestic medical centers].

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

Study on the preparation of granular alum sludge adsorbent for phosphorus removal.

Alum sludge is the sludge discharged from a sedimentation tank in a drinking water treatment plant when polymerized with poly-aluminum chloride (PAC). In this paper, granular alum sludge adsorbent (GASA) was manufactured using powdery alum sludge (PAS) as the raw material and methods such as gluing and pore-forming. The effects of different binders, pore-forming agents, roasting temperatures, and roasting times on the formation of GASA and its dephosphorization performance were investigated. Results showed that the optimum binder was AlCl3 at a mass ratio of 8%, and the best pore-forming agent was starch at a 4% dosage ratio. Meanwhile, the optimum roasting temperature and time were 500 °C and 2 hours, respectively. The specific surface area of GASA was 23.124 m2/g. Scanning electron microscopy suggested that GASA's surface became rough, particles became tight, and average pore size increased, with additional pore channels. P adsorption by GASA reached 0.90 mg/g. The effluent phosphorus concentration of actual tail water decreased to 0.49 mg/L and the removal rate reached 73.5% when the GASA dosage was 20 g/L. The findings of this study are important for the further development of a low-cost adsorbent material for P removal in the future.

A Retrospective Study of a Chinese Traditional Medicine YIKEER in the Treatment of Verruca Patients in Liaoning District.

BACKGROUND: There are many possible ways to treat verruca, but no one is the single perfect treatment. YIKEER is a kind of compound preparation of Chinese traditional medicine, which has been used in the treatment of verruca for several years. AIM: To confirm the effects of YIKEER for verruca. METHOD: Patients with verruca vulgaris, verruca plantaris, or verruca plana were instructed to apply YIKEER stock solution or diluent to the lesions once or twice daily for 5-7 days. Then, the YIKEER was ceased for 3-4 days, and sea buckthorn oil was used for wound repairing. The total procession was defined as one session. RESULT: Respective 88.05% verruca vulgaris patients, 86.03% verruca plantaris patients, and 82.42% verruca plana patients achieved complete response. Most patients gained complete or partial responses after 4 treatment sessions. The percentage of patients who achieved at least 50% improvement was 90.34% for verruca vulgaris, 90.60% for verruca plantaris, and 80.91% for verruca plana after 4-session treatment. The efficacy of verruca vulgaris or verruca plantaris was better than that of verruca plana. CONCLUSION: YIKEER is an effective, safe, and well-tolerated agent for treating verruca including verruca vulgaris, verruca plantaris, and verruca plana.

[Observation on the effects of multidisciplinary comprehensive intervention in integrated treatment of patients with extremely severe burns].

Objective: To explore the effects of multidisciplinary comprehensive intervention in integrated treatment of patients with extremely severe burns. Methods: One hundred and ten patients hospitalized in our center from July 2013 to August 2017 met the criteria for inclusion in this study, and their medical records were retrospectively analyzed. According to the medical model at that time, 56 patients hospitalized from July 2013 to July 2015 received routine comprehensive treatment led by doctors, and they were included in the conventional intervention group. From August 2015 to August 2017, 54 patients were treated with integrated multidisciplinary interventions performed by a team consisting of physicians, intensive care nurses, burn nurses, intravenous infusion nurses, wound stoma nurses, and rehabilitation therapists, and they were included in the integrated intervention group. Acute Physiological and Chronic Health Assessment Ⅱ (APACHE Ⅱ) scores on admission and 4 weeks after treatment, incidences of pressure injury, wound sepsis, lung infection, and catheter-related infection during hospitalization, length of stay in intensive care unit (ICU) and total length of hospital stay, and Abbreviated Burn Specific Health Scale (BSHS-A) scores at discharge and 3 months after discharge were analyzed. Data were processed with t-test and chi-square test. Results: The APACHE Ⅱ scores of patients in the two groups were close on admission (t=0.573, P>0.05). Four weeks after treatment, the APACHE Ⅱ scores of patients in the two groups were obviously lower than those on admission within the same group (t=5.697, 4.853, P<0.01), and the score of the integrated intervention group was obviously lower than that of the conventional intervention group (t=2.170, P<0.05). No pressure injury was observed in patients of any group during hospitalization. The incidences of wound sepsis, lung infection, and catheter-related infection of patients in the integrated intervention group were 18.5% (10/54), 3.7% (2/54), and 9.3% (5/54), respectively, significantly lower than 42.9% (24/56), 21.4% (12/56), and 26.8% (15/56) of the conventional intervention group, χ2=4.073, 6.075, 3.962, P<0.05. The length of stay in ICU of patients in the integrated intervention group was (50±5) d, obviously shorter than (62±4) d of the conventional intervention group (t=2.852, P<0.01). The total length of hospital stay of patients in the integrated intervention group was (115±8) d, obviously shorter than (140±7) d of the conventional intervention group (t=16.885, P<0.01). At discharge and 3 months after discharge, the scores of BSHS-A, physical function, psychological function, and general health status of 50 patients in the integrated intervention group were significantly higher than those of 48 patients in the conventional intervention group (t=2.886, 3.126, 2.416, 2.544, 2.033, 3.471, 2.588, 2.210, P<0.05 or P<0.01), while the scores of social function of patients in the two groups were close (t=1.570, 1.350, P>0.05). Conclusions: Integrative treatment of patients with extremely severe burns by multidisciplinary comprehensive intervention can significantly alleviate the severity of burns, reduce the incidences of wound sepsis, lung infection, and catheter-related infection, shorten the length of stay in ICU and total length of hospital stay, and improve the quality of life.

Microdomain elements of airway smooth muscle in calcium regulation and cell proliferation.

Airway remodeling manifested by hyperplasia of airway smooth muscle cells (ASMCs) and other structural and functional changes is a pathological condition in asthma not addressed by current treatment. Ca2+ signaling is crucial for ASMC proliferation. Inositol-1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) mediate Ca2+ release from endoplasmic reticulum/sarcoplasmic reticulum (ER/SR). Upon sensing the depletion of Ca2+ in ER/SR, stromal interaction molecule 1 (STIM1) aggregates and redistributes at the microdomain of ER/SR-plasma membrane (PM) and activates Orai1, a component of the store-operated Ca2+ (SOC) channels, to initiate Ca2+ influx. The STIM1/Orai1-mediated SOC entry is the main cause of a sustained intracellular calcium ([Ca2+]i) elevation, which is different from a transient rise of [Ca2+]i mediated by IP3R and RyR. Extended-synaptotagmin 1 (E-Syt1) is recruited to the ER/SR-PM junction and anchors to the PM lipid phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) in a SOC-dependent manner. The subsequent strengthening of the ER/SR-PM connection by E-Syt1 facilitates the phosphatidylinositol (PI) transfer protein, Nir2, to supplement PI, a PI(4,5)P2 substrate, for the generation of IP3 and the propagation of Ca2+ signaling. Calcineurin and nuclear factor of activated T cells are the downstream signaling factors of elevated [Ca2+]i contributing to ASMC proliferation. Mitochondrial Ca2+ uptake/efflux, mitochondrial fission/fusion and mitochondrial-ER/SR coupling also play important roles in modulating [Ca2+]i and ASMC proliferation. Together, these pathways and mechanisms represent new therapeutic targets for airway remodeling. The present review provides an overview of our current understanding of the mechanisms of ASMC proliferation involving Ca2+ and highlights potential directions to control airway remodeling in asthma.

Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats.

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg-1·day-1; and oral KXS at a dose of 676 mg·kg-1·day-1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1ß, IL-2, IL-4, IL-6, IL-10, TGF-ß, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg-1·day-1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg-1·day-1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

Intra-articular injection of microRNA-140 (miRNA-140) alleviates osteoarthritis (OA) progression by modulating extracellular matrix (ECM) homeostasis in rats.

OBJECTIVE: Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. DESIGN: miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. RESULTS: miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. CONCLUSION: Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.

[Effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.