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Objective Postdoctoral program in clinical medicine is a new approach to China's exploration of medical elite training. Since 2016, the Department of Surgery of Peking Union Medical College Hospital has explored and gradually established an advanced training system in order to cultivate clinical post-doctoral skills. The purpose of this research is to review and analyze the construction process and training effects of the advanced skill-raining system, and discuss the advantages of the training system and the direction of further improvement. Methods Postdoctoral students of surgical clinical medicine from 2016 to 2019 were evaluated and analyzed on surgical skills, results of the establishment of the system, and the output of scientific research. Results With the currently established preliminary system of progressively training surgical skills, three generations of 26 clinical postdoctoral trainees of surgery have been successfully trained. The surgical postdoctoral students trained by this system have significantly higher annual assessment results of surgical skills than training residents of the same year. In addition, during the establishment of this system, 19 teaching-related reform projects have been established, and 14 papers related to this system have been published. Conclusions The advanced training system of surgical skills has shown obvious advantages in the training process of surgical postdoctoral doctors. The construction and perfection of the system still needs to be further improved in combination with the actual needs of postdoctoral surgeons in surgery and the goal of standardized training for residents.

To observe the efficacy of acupoint sticking with Jianpi Tongjing Zhitong ointment in the treatment of functional dyspepsia due to liver-qi stagnation and spleen deficiency and its effect on serum 5-hydroxytryptamine (5-HT) and ghrelin contents. One hundred patients with functional dyspepsia due to liver-qi stagnation and spleen deficiency were divided into a treatment group and a control group by the random number table method, with 50 cases in each group. The treatment group received acupoint sticking with Jianpi Tongjing Zhitong ointment and the control group was treated with mosapride citrate orally. Patients were treated for 4 weeks as a course. The therapeutic efficacy was compared after one-course treatment and the differences in gastric emptying rate, and serum 5-HT and ghrelin contents between groups were compared before and after treatment. The total effective rate was 79.6% in the control group and 89.4% in the treatment group, showing significantly different between groups (P

Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades. However, optimal cell types and transplantation methods remain unclear. This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell (hUCMSC) sheet on myocardial infarction (MI). Methods hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells. We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet. Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system. Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, angiogenesis and left ventricular remodelling. Results When transplanted to the infarcted mouse hearts, hUCMSC sheet significantly improved the retention and survival compared with cell suspension. At the early stage of MI, hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages, preserving the cardiomyocytes from acute injury. Moreover, the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue, providing mechanical support and routes for revascularsation. These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI. Conclusions hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs, mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart. Translational perspective Due to its excellent availability as well as superior local cellular retention and survival, allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs, such as modulating inflammation and enhancing angiogenesis. Moreover, the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial, further improving its clinical applicability., Graphical abstract Image 1, Highlights • Cell sheet formation of hUCMSCs dramatically improves post transplantation cell survival in the infarcted heart. • hUCMSC sheet protects cardiomyocytes from infarction by alleviating acute inflammation. • The ECM of cell sheet serves as bioactive scaffold to allow the host cells to integrate and form new epicardial tissue. • The new epicardial tissue can provide mechanical support and new routes for revascularization.

With the development of human-computer interaction, how to use intelligent, natural and efficient methods to promote the development of the medical field has become a hot topic of research. Nervous system diseases have a great impact on the quality of people's daily life. Using the method of human-computer interaction for early warning and ancillary diagnosis of nervous system diseases can reduce discomfort of patients during exams and work intensity of doctors, which is of great significance to both doctors and patients. This paper discusses the application status, existing problems, future development of human-computer interaction in the ancillary diagnosis of nervous system diseases, and how to use computer technology to improve traditional medical diagnosis methods from the perspective of interaction.

Background Research shows that nano-bioceramics can modulate the differentiation of dental stem cells. The novel ready-to-use calcium-silicate-based root-canal sealer iRoot SP is widely used in root filling. Accordingly, the aim of this study was to evaluate the effects of iRoot SP on proliferation and osteogenic differentiation in human stem cells from the apical papilla (hSCAPs). Methods hSCAPs were isolated and characterized in vitro, then cultured with various concentrations of iRoot SP extract. Cell proliferation was assessed by CCK-8 assay, and scratch-wound-healing assays were performed to evaluate cell-migration capacity. hSCAPs were then cultured in osteogenic medium supplemented with iRoot SP extracts. Alkaline phosphatase (ALP) activity assay was used to evaluate ALP enzyme levels. Alizarin red staining and cetylpyridinium chloride (CPC) assays were performed to assess calcified-nodule formation and matrix-calcium accumulation of hSCAPs. The mRNA and protein expression levels of the osteogenic markers OCN, OSX, Runx2, and DSPP were determined by qRT-PCR and Western blotting. The data were analyzed using one-way ANOVA and LSD-t tests. Results iRoot SP at low concentrations (2, 0.2, and 0.02 mg/mL) is nontoxic to hSCAPs. iRoot SP at concentrations of 0.02 and 0.2 mg/mL significantly increases cell-migration capacity. In terms of osteogenic differentiation, 0.2 mg/mL iRoot SP promotes intracellular ALP activity and the formation of mineralized nodules. Moreover, the expression of osteogenic markers at the mRNA and protein levels are upregulated by iRoot SP. Conclusion iRoot SP is an effective filling material for periapical bone regeneration.

A chemical investigation on the roots of Aconitum episcopale afforded three undescribed aconitine-type C19-diterpenoid alkaloids, episcopalines A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vivo for their antinociceptive properties. As a result, episcopaline B (2) showed potent antinociceptive effect and its ID50 value (55.0 μmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Objectives The aim of this study was to evaluate the clinical outcomes of the Wiltse approach and percutaneous pedicle screw placement under O‐arm navigation for the treatment of thoracolumbar fracture. Methods We enrolled a total of 54 patients with neurologically intact thoracolumbar fracture who received minimally invasive treatments between October 2014 and October 2018 in this retrospective study. Among these, 28 patients (22 males and six females, with a mean age of 48.6 ± 9.6 years) were treated with pedicle screw fixation through the Wiltse approach (WPSF), and another 26 (15 males and 11 females, with a mean age of 45.7 ± 10.6 years) received percutaneous pedicle screw fixation under O‐arm navigation (OPSF). Statistical methods were used to perform a detailed comparison of clinical outcomes, radiologic findings, and complications between the two groups obtained preoperatively, postoperatively, and at last follow‐up. Results All patients underwent surgery successfully and finished a follow‐up of more than 12 months. No serious complications, such as infection, blood vessel injury, or spinal cord or nerve root injury occurred. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, local Cobb angle (LCA), vertebral wedge angle (VWA), and R value were notably improved after surgery, though there was no clear discrepancy between the groups at each time point (P > 0.05). During the follow‐up period, no patients developed neurological impairment or implant‐related complications, and no patients underwent revision surgery. The WPSF group had a significantly shorter operation time than the OPSF group (68.1 ± 9.8 vs 76.1 ± 9.0 minutes, P = 0.005). Moreover, the WPSF group showed less cost of surgery than the WPSF group (48142.1 ± 1430.1 vs 59035.4 ± 1152.7 CNY, P 0.05). The accuracy of pedicle screw placement was 95.2% (160/168) in the WPSF group and 96.8% (151/156) in the OPSF group, with no significant difference between the groups (P = 0.432). Conclusion Both WPSF and OPSF were safe and effective for the treatment of thoracolumbar fracture. Although the two groups showed favorable clinical and radiologic outcomes through to final follow‐up, we recommended the minimally invasive WPSF given its shorter operation time and lower cost of surgery., Both WPSF and OPSF were safe and effective for the treatment of thoracolumbar fracture. Although the two groups showed favorable clinical and radiologic outcomes through to final follow‐up, we recommended the minimally invasive WPSF given its shorter operation time and lower cost of surgery.

Background: The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. Methods: We developed a sensitive high-pressure liquid chromatography technique to quantify dietary GGPP and conducted proteomics, qualitative real-time polymerase chain reaction screening, and Western blot to determine signaling cascades, gene expression, protein–protein interaction, and protein membrane trafficking in wild-type and transgenic rats. Results: GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate–rich garlic extracts. In human pulmonary artery smooth muscle cells treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2 (Rho associated coiled-coil containing protein kinase 2)/Rab10 (Ras-related protein rab-10) signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and human pulmonary artery smooth muscle cells upregulated the expression of Ca 2+ -sensing receptor (CaSR) and HIMF (hypoxia-induced mitogenic factor), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10 knockdown almost abrogated hypoxia-promoted CaSR membrane trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed a high GGPP diet, blood GGPP levels were increased. This abolished statin-lowering effects on plasma GGPP, and also on hypoxia-enhanced RhoA activity of blood monocytes that was rescued by garlic extracts. Conclusions: There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of RhoA-ROCK2 cascade activation and Rab10-faciliated CaSR membrane trafficking with subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.

A chemical investigation of the 80% ethanol extract of the roots of Aconitum episcopale led to the isolation of two undescribed C19-diterpenoid alkaloids, designated as episcopines A and B. The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vivo for antinociceptive potential. Episcopine A showed a 2-fold more potent antinociceptive effect (ID50 = 66.1 μmol/kg) than the positive control drugs aspirin and acetaminophen.

Cu-diacetyl-bis (N4-methylthiosemicarbazone) (CuATSM) has both anti-oxidative and anti-inflammatory activities, but its therapeutic efficacy for oxidative stress has not been thoroughly investigated in acute ischemic stroke. Here, the present study was designed to assess the efficacies of CuATSM in acute ischemic stroke by comparing with the standard neuroprotective reagent edaravone. Mice were subjected to transient middle cerebral occlusion (tMCAO) for 60 min, and then intravenously administrated with CuATSM (1.5 mg/kg) or edaravone (3 mg/kg) just after the reperfusion, and examined at 1 and 3 d. Compared with the vehicle group, CuATSM treatment decreased infarct volumes and oxidative stress at 3d after tMCAO, which was further enhanced by combined CuATSM + edaravone treatment as compared with single CuATSM group, but not improve neurobehaviors. The present study demonstrated that CuATSM showed strong antioxidative and neuroprotective effects in acute ischemic stroke, which was enhanced by the combination with edaravone.

To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P

Rock creep properties can be used to predict the long-term stability in rock engineering. In reservoir bank slopes, sandstones which are frequently used in the bank slope undergoing long-term effects of dry-wet (DW) cycles due to periodic water inundation and drainage may gradually accumulate creep deformation, resulting in rock structure’s damage or even geological hazards such as landslides. To fully investigate the effect of DW cycles on the creep damage properties of sandstone, triaxial creep tests were conducted on saturated sandstone with different DW cycles by using a triaxial rheometer apparatus. The experimental results show that both the instantaneous strain and the stabilized strain increase with the DW cycles. In addition, using the Burgers model, four kinds of functions including an exponentially decreasing function, a linearly decreasing function, a linearly increasing function and an exponentially increasing function were proposed to express the relationships between the shear modulus, viscoelastic parameters of the Burgers model and the deviatoric stress under different DW cycles. Through comparative analysis, it is found that the theoretical curves generated using proposed four kinds of functions are in good agreement with the experimental data. Furthermore, macromorphological and microstructural observations were performed on specimens after various triaxial rheological tests. For samples with small number of DW cycles, approximately X-shaped fracture surfaces were observed in shear failure zones, whereas several shear fractures including obvious axial and horizontal tensile cracks, and flaws were found for samples with relatively large DW cycles due to long-term propagation and evolution of micro-fissures and micro-pores. Furthermore, as the DW cycles increases, the variation in micro-structure of samples after creep failure was summarized into three stages, namely, a stage with good and dense structure, a stage with pore and fissure propagation, and a stage with extensive increase of pores, fissures and loose particles. It is concluded that the combination effect of permeation of water molecules through pores and fissures within sandstone, and the propagation of preexisting pores and fissures owing to the dissolution of mineral particles leads to further deterioration of the mechanical properties of sandstone as the number of DW cycles increases. This study provides a fundamental basis for evaluating the long-term stability of reservoir bank slopes under cyclic fluctuations of water level.

This phase 1 study characterized the effect of multiple doses of upadacitinib, an oral Janus kinase 1 selective inhibitor, on the pharmacokinetics of the cytochrome P450 (CYP) 2B6 substrate bupropion. Healthy subjects (n = 22) received a single oral dose of bupropion 150 mg alone (study period 1) and on day 12 of a 16‐day regimen of upadacitinib 30 mg once daily (study period 2). Serial blood samples for measurement of bupropion and hydroxybupropion plasma concentrations were collected in each study period. The central values (90% confidence intervals) for the ratios of change were 0.87 (0.79‐0.96) for bupropion maximum plasma concentration (Cmax), 0.92 (0.87‐0.98) for bupropion area under the plasma‐concentration time curve from time 0 to infinity (AUCinf), 0.78 (0.72‐0.85) for hydroxybupropion Cmax, and 0.72 (0.67‐0.78) for hydroxybupropion AUCinf when administered with, relative to when administered without, upadacitinib. After multiple‐dose administration of upadacitinib 30 mg once daily, upadacitinib mean ± SD AUC0‐24 was 641 ± 177 ng·h/mL, and Cmax was 83.3 ± 30.7 ng/mL. These results confirm that upadacitinib has no relevant effect on pharmacokinetics of substrates metabolized by CYP2B6.

Aim: A sensitive and reliable LC–MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug–drug interactions occurred between RIV and TAK-438 when co-administered to rats.

Stem cell-derived sheet engineering has been developed as the next-generation treatment for myocardial infarction (MI) and offers attractive advantages in comparison with direct stem cell transplantation and scaffold tissue engineering. Furthermore, induced pluripotent stem cell-derived cell sheets have been indicated to possess higher potential for MI therapy than other stem cell-derived sheets because of their capacity to form vascularized networks for fabricating thickened human cardiac tissue and their long-term therapeutic effects after transplantation in MI. To date, stem cell sheet transplantation has exhibited a dramatic role in attenuating cardiac dysfunction and improving clinical manifestations of heart failure in MI. In this review, we retrospectively summarized the current applications and strategy of stem cell-derived cell sheet technology for heart tissue repair in MI.

Alzheimer's disease (AD) and chronic cerebral hypoperfusion (CCH) often coexist in dementia patients in aging societies. The hallmarks of AD including amyloid-β (Aβ)/phosphorylated tau (pTau) and pathology-related events such as neural oxidative stress and neuroinflammation play critical roles in pathogenesis of AD with CCH. A large number of lessons from failures of drugs targeting a single target or pathway on this so complicated disease indicate that disease-modifying therapies targeting multiple key pathways hold potent potential in therapy of the disease. In the present study, we used a novel mouse model of AD with CCH to investigate a potential therapeutic effect of a free radical scavenger, Edaravone (EDA) on AD with CCH via examining motor and cognitive capacity, AD hallmarks, neural oxidative stress, and neuroinflammation. Compared with AD with CCH mice at 12 months of age, EDA significantly improved motor and cognitive deficits, attenuated neuronal loss, reduced Aβ/pTau accumulation, and alleviated neural oxidative stress and neuroinflammation. These findings suggest that EDA possesses clinical and pathological benefits for AD with CCH in the present mouse model and has a potential as a therapeutic agent for AD with CCH via targeting multiple key pathways of the disease pathogenesis.

Alzheimer's disease (AD) in the elderly is frequently accompanied by chronic cerebral hypoperfusion (CCH), which impairs the clearance of amyloid beta (Aβ) due to the dysfunction of the blood–brain barrier (BBB) and accelerates the AD pathology. Since the coagulation and complement cascades are associated with BBB dysfunction and AD pathology, we investigated the expression changes of coagulation (fibrinogen alpha chain-FGA, coagulation factor XIII A chain-Factor XIIIα) and complement (plasma protease C1 inhibitor-C1-INH, Complement component 3-C3) factors in the brain of novel AD model (APP23) mice with CCH at 12 months of age. Immunohistochemical and immunofluorescent analysis showed that the expressions of FGA, Factor XIIIα, C1-INH and C3 were significantly increased in cerebral neocortex, hippocampus, and thalamus of APP23 + CCH group (n = 12) as compared with wild type (WT, n = 10) and APP23 (n = 10) groups (⁎P

Hypoxia inducible factor-1α (HIF-1α) is a key transcription factor that maintains oxygen homeostasis. Hypoxic stress is related to the pathogenesis of amyotrophic lateral sclerosis (ALS), and impaired HIF-1α induces motor neuron degeneration in ALS. Dimethyloxalylglycine (DMOG) upregulates the stability of HIF-1α expression and shows neuroprotective effects, but has not been used in ALS as an anti-hypoxic stress treatment. In the present study, we investigated hypoxic stress in ALS model mice bearing G93A-human Cu/Zn superoxide dismutase by in vivo HIF-1α imaging, and treated the ALS mice with DMOG. In vivo HIF-1α imaging analysis showed enhanced hypoxic stress in both the spinal cord and muscles of lower limbs of ALS mice, even at the pre-symptomatic stage. HIF-1α expression decreased as the disease progressed until 126 days of age. DMOG treatment significantly ameliorated the decrease in HIF-1α expression, the degeneration of both spinal motor neurons and myofibers in lower limbs, gliosis and apoptosis in the spinal cord. This was accompanied by prolonged survival. The present study suggests that in vivo bioluminescence resonance energy transfer (BRET) HIF-1α imaging is useful for evaluating hypoxic stress in ALS, and that the enhancement of HIF-1α is a therapeutic target for ALS patients.

A simple, rapid, and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous quantitation of PA-824 and moxifloxacin in rat plasma using carbamazepine as an internal standard (IS). The sample preparation involved a one-step protein precipitation method with methanol. The separation was performed on Inertsil® ODS3 C18 column (150 mm × 4.6 mm, 5 μm) and maintained at 30 °C. The mobile phase consisted of 0.1% formic acid in acetonitrile–water (90:10 v/v) with fast isocratic elution at a flow rate of 0.6 mL/min and a run time of 10 min. A mass spectrometer was run in the positive ion electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The MRM transitions were chosen to be m/z 360.1 → m/z 175.0 for PA-824, m/z 402.0 → m/z 383.9 for moxifloxacin, and m/z 237.1 → m/z 194.0 for IS. The method was fully validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recover...

The aim of this study was to characterize the effects of upadacitinib, a Janus kinase 1 inhibitor, on in vivo activity of different cytochrome P450 (CYP) enzymes using a cocktail approach. Healthy subjects (n = 20) received single oral doses of the modified Cooperstown 5+1 cocktail drugs (midazolam [CYP3A], caffeine [CYP1A2], warfarin + vitamin K [CYP2C9], omeprazole [CYP2C19], and dextromethorphan [CYP2D6]) without upadacitinib and on day 11 (midazolam) or 12 (all other probes) of a 15‐day regimen of upadacitinib 30 mg once daily (extended‐release formulation). Serial blood samples and 12‐hour urine samples were collected for assays of the probe substrates and select metabolites. The ratio (90%CI) of area under the plasma concentration‐time curve from time 0 to infinity (AUCinf) central values when the cocktail drugs were administered with upadacitinib relative to when administered alone were 0.74 (0.68‐0.80) for midazolam, 1.22 (1.15‐1.29) for caffeine, 1.11 (1.07‐1.15) for S‐warfarin, 1.07 (0.95‐1.22) for dextromethorphan, and 0.82 (0.72‐0.94) for omeprazole. The ratio (90%CI) was 1.09 (1.00‐1.19) for 5‐hydroxy‐omeprazole to omeprazole AUCinf ratio and 1.17 (0.97‐1.41) for dextromethorphan to dextrorphan 12‐hour molar urinary ratio. Upadacitinib 30 mg once daily (a dose that is twice the optimal dose in rheumatoid arthritis based on phase 3 results) has a limited effect on CYP3A activity (26% decrease in exposure of midazolam, a sensitive CYP3A substrate) and no relevant effects on CYP1A2, CYP2C9, CYP2C19, or CYP2D6 activity in vivo. No clinically relevant changes in plasma exposures are expected for drugs that are substrates for the evaluated CYP enzymes when coadministered with upadacitinib.

To compare the therapeutic efficacy between warm needling moxibustion and electroacupuncture (EA) in the treatment of simple obesity due to yang deficiency of the spleen and kidney. Seventy patients with simple obesity due to yang deficiency of the spleen and kidney were randomly divided into a warm needling moxibustion group and an EA group, with 35 subjects in each group. Same major acupoints were selected for the two groups, including Shuifen (CV 9), Guanyuan (CV 4), Daheng (SP 15), Shuidao (ST 28), Shousanli (LI 10), Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3). The warm needling moxibustion group received warm needling moxibustion, while the EA group received EA treatment. The interventions were performed once every other day, with 15 treatments as one course. The therapeutic efficacy, body weight and body mass index (BMI) were then observed and compared. The total effective rate in the warm needling moxibustion group was 85.7% versus 77.1% in the EA group, and the between-group difference was statistically significant (P

Alzheimer's disease (AD) is the most common dementia and a progressive neurodegenerative disorder aggravated by chronic hypoperfusion (HP). Since numerous evidence suggests that inflammation is related with AD pathology, we investigated the expression change of two anti-inflammatory markers, inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and alpha-2-HS-glycoprotein (AHSG), in a novel AD model (APP23) with HP at 12 month of age. As compared with wild type (WT, n = 10), immunohistochemical analysis showed a higher ITIH4 and a lower AHSG expressions in the cerebral cortex, hippocampus, and thalamus of the APP23 + HP group (n = 12) than the simple APP23 (n = 10) group (*p

Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the treatment of several inflammatory autoimmune diseases, including rheumatoid arthritis. Upadacitinib is a nonsensitive substrate for metabolism by cytochrome P450 3A enzymes. This open‐label, single‐dose, multicenter study assessed the pharmacokinetics of upadacitinib following oral administration of a single 15‐mg dose of the upadacitinib extended‐release formulation in subjects with mild (n = 6) and moderate (n = 6) hepatic impairment relative to demographically matched healthy subjects (n = 6). Subjects were assigned to 1 of the 3 groups according to the Child‐Pugh classification. Relative to subjects with normal hepatic function, the ratios (90% confidence intervals) of upadacitinib area under the plasma concentration‐versus‐time profile from time 0 to infinity (AUCinf) for subjects with mild and moderate hepatic impairment were 1.28 (0.91‐1.79) and 1.24 (0.87‐1.76), respectively. The central ratios of upadacitinib maximum observed concentration (Cmax) were 1.04 (0.77‐1.39) and 1.43 (1.05‐1.95) in subjects with mild and moderate hepatic impairment, respectively, compared with subjects with normal hepatic function. No clinically significant changes in vital signs or hematology measurements were observed, and no new safety events were identified in this study. These results indicate that mild and moderate hepatic impairment has no clinically relevant effect on upadacitinib pharmacokinetics.

The aim of this review is to identify the worldwide trend of waterborne protozoan outbreaks and how it varies between geographic regions during the period from 2017 to 2020. Data about waterborne protozoan outbreaks were gathered and stratified by continent, country, water source, and protozoan species associated with the outbreak. The highest prevalence of waterborne protozoan outbreaks was reported in developed countries. Out of 251 outbreaks reported worldwide during the studied period, 141, 51 and 24 outbreaks were recorded in the USA, UK, and New Zealand, respectively. These outbreaks were mainly associated with Cryptosporidium (192 outbreaks) and Giardia (48 outbreaks). Cyclospora cayetanensis, Dientamoebafragilis and Toxoplasma gondii were associated with 7 outbreaks. One outbreak was associated with each of Blastocystis hominis, Entamoeba histolytica, Microsporidia or Naegleria fowleri. This data suggests large discrepancies in the number of outbreaks reported between geographic regions, with most outbreaks recorded in developed countries. Differences in the prevalence of outbreaks between countries are likely attributed to the availability of diagnostic capabilities and surveillance programs to monitor water contamination with pathogenic protozoa. More attention and concerted efforts are required to improve water safety and to alleviate the impact of waterborne protozoan infections. Appropriate surveillance of water contamination with protozoa can enable public health officials to identify source of contamination and implement the necessary measures to limit transmission and prevent outbreaks.

We present an automatic lumen segmentation method using uniqueness of connected region for intravascular optical coherence tomography (IVOCT), which can effectively remove the effect on lumen segmentation caused by blood artifacts. Utilizing the uniqueness of vascular wall on A-lines, we detect the A-lines shared by multiple connected regions, identify connected regions generated by blood artifacts using traversal comparison of connected regions' location, shared ratio and area ratio and then remove all artifacts. We compare these three methods by 216 challenging images with severe blood artifacts selected from clinical 1076 IVOCT images. The metrics of the proposed method are evaluated including Dice index, Jaccard index and accuracy of 94.57%, 90.12%, 98.02%. Compared with automatic lumen segmentation based on the previous morphological feature method and widely used dynamic programming method, the metrics of the proposed method are significantly enhanced, especially in challenging images with severe blood artifacts.

Studies have found that athletes outperformed non-athletes in mental rotation tasks with both object-based and egocentric transformations (ET), but the effect of sport expertise on the processing stages (i.e., perceptual stage, rotation stage, and decision stage) remains conflicted. Bearing the view that the stages occur sequentially and the high temporal resolution of event-related brain potentials, this study focused on brain processing during mental rotation and was designed to determine the time course of electrophysiological changes in athletes and non-athletes. A total of 42 divers and non-athletes were recruited for the study. A mental body rotation task with object-based and egocentric transformation conditions was conducted, and the reaction time (RT), accuracy, performance stages, N2 latency, amplitude, and the amplitude of rotation-related negativity (RRN) were recorded. Behavioral results demonstrated higher accuracy for athletes at 120° and 180°. Moreover, as compared to non-athletes, the enlarged amplitude of N2 and RRN were confirmed in both transformations for athletes and were correlated with the performance stages and athletes’ professional training years. The present study provided a deeper insight into the relationship between sports training, behavior performance, and brain activity.

Background To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique. Methods Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively. Results A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE. Conclusions EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.

Vitamin D (VD) deficiency seems to be associated with the risk of recurrent spontaneous abortion (RSA). Vitamin D receptor (VDR) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) are two genes which are vital for VD metabolism and actions. However, whether single-nucleotide polymorphisms (SNPs) in these genes are correlated with the risk of RSA are poorly understood. Therefore, we aimed to characterize the relationships among VDR SNPs, CYP2R1 SNPs and RSA. This case–control study enrolled 75 RSA patients and 83 controls. Serum VD and some cytokines were detected with LC–MS/MS and flow cytometry, respectively. Genotyping for three SNPs of CYP2R1 (rs10741657, rs10766197 and rs12794714) and five SNPs of VDR (rs7975232, rs1544410, rs2189480, rs2228570 and rs2239179) was done with polymerase chain reaction (PCR) and high-throughput sequencing. All the data were analyzed with appropriate methods and in different models. The results revealed a significant correlation between the AG genotype of CYP2R1 rs12794714 and VD levels (OR 0.686; 95% CI 0.49–0.96; p = 0.028). Besides, the AG and GG genotypes of CYP2R1 rs12794714 were markedly related to the risk of RSA (OR 52.394, 59.497; 95% CI 2.683–1023.265, 3.110–1138.367; p = 0.009, 0.007, respectively). Our results indicate that CYP2R1 rs12794714 might be a risk factor for RSA. Hence, early screening of pregnant women for CYP2R1 rs12794714 is necessary to warrant proactive counseling and treatment against RSA.

Although strict mitigation measures have been implemented since 2013 in Beijing-Tianjin-Hebei (BTH), China, air pollution still frequently occurs. Observations reveal that during pollution episodes in autumn, fine particulate matter (PM2.5) concentrations have not decreased, and particularly, ozone (O3) concentrations have increased remarkably from 2013 to 2015 in Beijing. Additionally, a concurrence of O3 and particulate pollution with high secondary aerosol contributions has been observed frequently, indicating high atmospheric oxidizing capacity (AOC) during particulate pollution. The WRF-Chem model simulations show elevated O3 concentrations and high fractions of oxygenated secondary aerosols (OSA) in PM2.5 (0.53–0.73) during the severe pollution period. During daytime there exhibits an AOC-sufficient regime with the persistently high OSA fraction and an AOC-deficient regime with varied OSA fractions, separated by the O3 level of 80 μg m−3. Our results suggest that increasing AOC can considerably weaken the emission mitigation effort by enhancing the secondary aerosol formation

Scallop-derived plasmalogen (sPlas) has both anti-oxidative and anti-inflammation activities, but its efficacy has not been investigated in ischemic stroke models where oxidative stress, inflammation, and neurovascular unit (NVU) damage accelerates pathophysiological progression. Therefore, in the present study, we aimed to assess the neuroprotective effects of sPlas in ischemic stroke by using a transient middle cerebral artery occlusion (tMCAO) mouse model. After the pretreatment of vehicle or sPlas (10 mg/kg/day) for 14 days, adult male mice were subjected to tMCAO for 60 min, then continuously treated with vehicle or sPlas during reperfusion and for an additional 5 days. The administration of sPlas significantly improved motor deficits (corner and rotarod tests, *p 0.05 vs vehicle), enhanced serum antioxidative activity (OXY-adsorbent and d-ROMs tests, *p 0.05 vs vehicle), reduced infarction volume (*p 0.05 vs vehicle), decreased the expression of two oxidative stress markers, 4-HNE (*p 0.05 vs vehicle) and 8-OHdG (*p 0.05 vs vehicle), decreased the expression of pro-inflammatory markers Iba-1 (**p 0.01 vs vehicle), IL-1β (**p 0.01 vs vehicle), and TNF-α (**p 0.01 vs vehicle), and alleviated NVU damage (collagen IV, MMP9, and GFAP/collagen IV, *p 0.05 vs vehicle). Our present findings are the first to demonstrate the neuroprotective effects of sPlas on acute ischemic stroke mice at 5 d after tMCAO via anti-oxidative stress, anti-inflammation, and improvement of NVU damage, suggesting the potential of sPlas in preventing and treating ischemic stroke.

This phase 1, 2‐part, 2‐period, open‐label, drug‐drug interaction study evaluated the potential for pharmacokinetic interactions between upadacitinib and rosuvastatin, an organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein substrate, or atorvastatin, a cytochrome P450 3A, OATP1B1, and OATP1B3 substrate, in 36 healthy volunteers. During period 1, a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered on day 1, followed by a washout period of 5 days. During period 2, once‐daily doses of upadacitinib extended‐release (30 mg) were administered on days 1 to 10, and a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered 1 hour after the upadacitinib dose on day 7. Serial blood samples were collected for assays of drug concentrations. In Part 1, rosuvastatin maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to infinity (AUCinf) were 23% and 33% lower, respectively, when administered with upadacitinib relative to when administered alone. In part 2, atorvastatin Cmax and AUCinf was 11% and 23% lower, respectively, when administered with upadacitinib relative to when administered alone. The Cmax and AUCinf of the active metabolite ortho‐hydroxyatorvastatin remained unchanged. Administration of a single 5‐mg dose of rosuvastatin or a single 10‐mg dose of atorvastatin had no relevant effect on upadacitinib Cmax or area under the plasma concentration–time curve. These results demonstrated that upadacitinib has no clinically relevant effect on the pharmacokinetics of rosuvastatin and atorvastatin or on substrates transported by OATP1B or breast cancer resistance protein.

Radiotherapy plays a vital role in treating patients with esophageal cancer (EC), whereas potential complications such as esophageal fistula (EF) can be devastating and even life-threatening. Therefore, predicting EF risks prior to radiotherapies for EC patients is crucial for their clinical treatment and quality of life. We propose a novel method of combining thoracic Computerized Tomography (CT) scans and clinical tabular data to improve the prediction of EF risks in EC patients. The multimodal network includes encoders to extract salient features from images and clinical data, respectively. In addition, we devise a self-attention module, named VisText, to uncover the complex relationships and correlations among different features. The associated multimodal features are integrated with clinical features by aggregation to further enhance prediction accuracy. Experimental results indicate that our method classifies EF status for EC patients with an accuracy of 0.8366, F1 score of 0.7337, specificity of 0.9312 and AUC of 0.9119, outperforming other methods in comparison.

White matter lesions (WMLs) caused by cerebral chronic hypoperfusion (CCH) may contribute to the pathophysiology of Alzheimer’s disease (AD). However, the underlying mechanisms and therapeutic approaches have yet to be totally identified. In the present study, we investigated a potential therapeutic effect of the free radical scavenger edaravone (EDA) on WMLs in our previously reported novel mouse model of AD (APP23) plus CCH with motor and cognitive deficits. Relative to AD with CCH mice at 12 months (M) of age, EDA strongly improved CCH-induced WMLs in the corpus callosum of APP23 mice at 12 M by improving the disruption of white matter integrity, enhancing the proliferation of oligodendrocyte progenitor cells, attenuating endothelium/astrocyte unit dysfunction, and reducing neuroinflammation and oxidative stress. The present study demonstrates that the long-term administration of EDA may provide a promising therapeutic approach for WMLs in AD plus CCH disease with cognitive deficits.

The purpose of this study was to investigate the effects of physical exercise tapping high-level cognitive functions on both cognitive function and fitness in older adults. In total, 96 healthy older adults took part in the study. Participants were randomly assigned to four groups: a cognitive training group (CG), physical exercise group (PG), simultaneous cognitive training and physical exercise group (C+PG), and the healthy control group (HG; received physical exercise materials but did not participate in a cognitive or exercise programme). The outcomes were the changes in the 6-minute walk test (6MWT), timed up-and-go (TUG) test, and the computerized modified Stroop task, which included two conditions, a naming condition (nonexecutive) and an executive condition. The results showed that the dynamic balance, cardiorespiratory endurance, and physical activity levels of the PG and C+PG were significantly better than those of the HG after the 12-week intervention. The times of the TUG test in these two groups were also significantly faster than those in the HG. Additionally, the C+PG exhibited better dual-task function than the PG. Over 12 weeks, the CG, PG, and C+PG demonstrated improved performance of executive function, but only the C+PG showed a general facilitative effect on nonexecutive control. Physical exercise tapping high-level cognitive functions and cognitive training can thus improve executive function more quickly than physical exercise alone. Moreover, physical exercise tapping high-level cognitive functions showed better fitness improvement than cognitive training alone, especially in dynamic balance.