Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ ^-/- colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.

OBJECTIVE: This study investigated the association between household chemical use and respiratory disease (RD) in older Chinese adults. METHODS: The data were from the 2018 China Longitudinal Health and Longevity Survey (CLHLS) database, which included 12,866 participants aged ≥ 65 years. The prevalence of RD was based on self-reported medical history, and patients were divided into diseased and non-diseased groups. The frequency of household chemical usage was divided into four categories, and a total score for eight household chemical usage categories was constructed. Binary logistic regression was used to determine the relationship between the frequency of household chemical use and RD, and a restricted cubic spline was used to determine the dose-response association. RESULT: After adjusting for all covariates, regular use of repellents [odds ratios ( OR) = 1.28, 95% CI 1.06-1.55] and oil removers ( OR = 1.28, 95% CI 1.03-1.58) were associated with RD. There was a dose-response association between the total score of household chemicals usage and RD risk ( P non-linearity > 0.05, P for trend < 0.01). Using patients with the total score below 9 as a reference, the OR for patients with the total score ranging from 25 to 32 is 2.33 (95% CI 1.25-4.09). CONCLUSION Regular use of repellents and oil removers increased the risk of RD, and the dose-dependent relationship was also observed.
Humans ; China/epidemiology* ; Aged ; Male ; Female ; Respiratory Tract Diseases/chemically induced* ; Aged, 80 and over ; Household Products/adverse effects* ; Prevalence

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

OBJECTIVE To study the anti-inflammatory immune response effects of lactoferrin in the treatment of periodontitis and its mechanism. METHODS One hundred SD rats were randomly divided into blank control group, model group, lactoferrin administration group low, medium, high dose group(1, 2, 3 g·kg-1), metronidazole positive control group (0.02 g·kg-1), PDTC group(200 mg·kg-1), lactoferrin+PDTC group(2 g·kg-1, 200 mg·kg-1), MCC950 group(1 mg·kg-1) and lactoferrin+MCC950 group(2 g·kg-1, 1 mg·kg-1), 10 rats in each group. Silk thread ligation combined with 10% sucrose drinking water was used to establish the model, and then the drug was administered orally once a day. The blank control group and the model group were administered orally with 0.9% NaCl. The rats in each group were sacrificed after one month of continuous administration. The contents of IL-1b, IL-8 and IL-10 were detected by ELISA kit, and the expressions of TLR2-NF-κB pathway and NLRP3 inflammasome related proteins were detected by Western blotting. HE staining was used to observe the pathological changes of the periodontal tissues of the rats in each group. RESULTS Compared with the model group, the symptoms of periodontitis in each dose group of lactoferrin were significantly improved. HE staining showed that the infiltration of inflammatory cells was reduced, and the proliferation of fibroblasts was active. The protein expressions of TLR2, NF-κB, NLRP3, Caspase-1 p20 and GSDMD-N decreased, the content of pro-inflammatory factor IL-8 and IL-1b decreased, and the content of anti-inflammatory factor IL-10 increased. CONCLUSION Lactoferrin may play a role in the regulation of inflammatory immune response in the treatment of periodontitis by down-regulating the protein expression of TLR2-NF-κB-NLRP3 pathway, reducing the initiation of inflammatory response and the release of inflammatory factors, so as to achieve the purpose of anti-inflammatory.

Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

Objective To compare the effects of general anesthesia and spinal anesthesia on prognosis of cesarean section in parturients with medium and severe pulmonary arterial hypertension (PAH).Methods Parturients with medium and severe PAH,at ≥ 24 weeks of gestation,aged 20-45 yr,undergoing elective cesarean section under general or epidural anesthesia from November 1,2011 to December 31,2017 in our hospital,were divided into general anesthesia group and epidural anesthesia group according to the anesthetic method.General anesthesia was combined intravenous-inhalational anesthesia.The highest temperature within 5 days after surgery,the lowest SpO2 (inhaling oxygen 2-4 L/min via a nasal tube) within 3 days after surgery,duration of intensive care unit stay,time of postoperative use of antibiotics,requirement for targeted drugs for pulmonary hypertension,results of laboratory tests (blood biochemistry,coagulation function),postoperative mechanical ventilation,length of hospital stay,and hospitalization costs were recorded.The Apgar score and weight of the newborn,postoperative complications and death of the newborn and parturients in hospital were recorded.Cox regression analysis was used to identify the risk factors after cesarean section in parturients with medium and severe PAH.Results Fifty-seven parturients were enrolled in this study,with 21 cases in general anesthesia group and 36 cases in epidural anesthesia group.Compared with general anesthesia group,the rate of postoperative mechanical ventilation was significantly decreased,the incidence of adverse events of parturients in hospital and mortality rate were decreased,the postoperative level of albumin was increased,activated partial thromboplastin time was shortened (P＜0.05),and no significant change was found in the other parameters in epidural anesthesia group (P＞ 0.05).The results of Cox regression analysis showed that anesthetic method and preoperative SpO2difference were independent risk factors for cesarean section-related adverse events and death of parturients with medium and severe PAH.The risk of adverse events and death of parturients was significantly higher in general anesthesia group than in epidural anesthesia group (P＜0.05).Conclusion Epidural anesthesia produces better prognosis than general anesthesia when used for cesarean section in parturients with moderate and severe PAH.

Based on ancient literature of acupuncture in Canon of Chinese Medicine (4th edition), the articles regarding acupuncture for urinary incontinence were retrieved and collected to establish a database. By Weka data mining software, the multi-level association rules analysis method was applied to analyze the acupoints selection characteristics and rules of ancient acupuncture for treatment of urinary incontinence. Totally 356 articles of acupuncture for urinary incontinence were collected, involving 41 acupoints with a total frequency of 364. As a result, (1) the acupoints in the yin-meridian of hand and foot were highly valued, as the frequency of acupoints in yin-meridians was 2.6 times than that in yang-meridians, and the frequency of acupoints selected was the most in the liver meridian of foot-jueyin; (2) the acupoints in bladder meridian of foot-taiyang were also highly valued, and among three yang-meridians of foot, the frequency of acupoints in the bladder meridian of foot-taiyang was 54, accounting for 65.85% (54/82); (3) more acupoints selected were located in the lower limbs and abdomen; (4) specific acupoints in above meridians were mostly selected, presenting 73.2% (30/41) to the ratio of number and 79.4% (289/364) to the frequency, respectively; (5) Zhongji (CV 3), the front-mu point of bladder meridian, was seldom selected in the ancient acupuncture literature, which was different from modern literature reports. The results show that urinary incontinence belongs to external genitalia diseases, which should be treated from yin, indicating more yin-meridians be used and special acupoints be focused on. It is essential to focus inheritance and innovation in TCM clinical treatment, and applying data mining technology to ancient literature of acupuncture could provide classic theory basis for TCM clinical treatment.
Acupuncture Points ; Acupuncture Therapy ; history ; China ; Data Mining ; Databases, Bibliographic ; history ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Humans ; Medicine in Literature ; Urinary Incontinence ; history ; therapy

Objective To assess the effect of different ages on sufentanil pharmacokinetics in patients undergoing cardiac valve replacement.Methods Sixteen NYHA Ⅱ or Ⅲ patients undergoing selective cardiac valve replacement were randomly divided into two groups:elderly group (aged 65-69 years,group Ⅰ,n =8) and young adult group (aged 36-45 years,group Ⅱ,n =8).Intravenous and intra-arterial cannulae were placed.Sufentanil 5 μg/kg injected intravenously during anesthesia induction.Blood samples from the radial artery were obtained at 1,3,5,10,20,30,60,120,180,240 and 360 min after sufentanil injection (3 ml each).Then 1 ml plasma was immediately separated from the 3 ml blood sample and stored at - 80 ℃ until being assayed.Plasma sufentanil concentration was determined with liquid chromatography mass spectrometry and pharmacokinetic parameters were calculated with 3P97 pharmacologicl program.Results Plasma sufentanil concentration versus the time decay curve in patients undergoing cardiac valve replacement before cardiopulmonary bypass (CPB) was fitted to a twocompartment model and could be expressed by bi-exponential equations:Cp (t) =27.4 e-0.41t + 3.2 e-0.029t in group Ⅰ and Cp (t) =14.4 e-0.51t +3.4 e-0.032t in group Ⅱ,respectively.There were significant differences in t 1/2 α,t1/2 β and CL between the two groups ( P ＜ 0.05 or 0.0l ).During CPB,plasma sufentanil concentration versus the time decay curve in patients undergoing cardiac valve replacement was fitted to a three-compartment model and could be expressed by tri-exponential equations:Cp(t) =22 e-0.51t + 3.5 e-0.045t + 0.21 e-0.0029 t in group Ⅰand Cp(t) =15 e-0.52t + 3.9 e-0.048t + 0.32 e-0.004t in group Ⅱ,respectively.There were no significant differences in pharmacokinetic parameters between the two groups ( P ＞ 0.05).Conclusion There are significant differences in sufentanil phannacokinetic characteristics before CPB but different ages have no obvious influence on sufentanil pharmaco-kinetics during CPB.

This study aimed to examine the preparation of cationic lipid microbubble (CLM),and evaluate its physical and chemical properties and toxicity,measure the gene transfection efficiency by ultrasound triggered microbobble destruction (UTMD) in combination with CLM.The CLM was prepared by the method of the thin film hydration,and its morphology was observed under the electron microscopy at 1st,3rd,7th,10th,and 14th day after preparation,respectively.The size,Zeta potential and stability of CLM were tested.The acute toxicity of CLM was assessed.The green fluorescent protein gene (EGFP) transfection efficiency was evaluated.The experiment grouping was as follows:naked plasmid group (P group),ultrasonic irradiation plus naked plasmid group (P-US group),naked plasmid plus CLM group (P-CLM group),naked plasmid plus ultrasound and CLM group (UTMD group).The expression of EGFP was detected by fluorescent microscopy and flow cytometry.The results showed that CLMs were spherical in shape,with the similar size and good distribution degree under the light and electron microscopies.The size of CLMs was varied from 250.4±88.3 to 399.0±99.8 nm and the Zeta potential of CLMs from 18.80±4.97 to 20.1 ±3.1 mV.The EGFP expression was the strongest in the UTMD group,followed by the P-CLM group,P-US group and P group.Flow eytometry results were consistent with those of fluorescent microscopy.The transfection efficiency was substantially increased in the P-US group,P-CLM group and UTMD group as compared with that in the P group,almost 7 times,10 times and 30 times higher than that in the P group respectively.It is suggested that CLMs prepared by the method of thin film hydration are uniform in diameter,and proved non-toxic.UTMD combined with CLM can significantly increase the transfection efficiency of EGFP to targeted cells.

This study aimed to examine the preparation of cationic lipid microbubble (CLM), and evaluate its physical and chemical properties and toxicity, measure the gene transfection efficiency by ultrasound triggered microbobble destruction (UTMD) in combination with CLM. The CLM was prepared by the method of the thin film hydration, and its morphology was observed under the electron microscopy at 1st, 3rd, 7th, 10th, and 14th day after preparation, respectively. The size, Zeta potential and stability of CLM were tested. The acute toxicity of CLM was assessed. The green fluorescent protein gene (EGFP) transfection efficiency was evaluated. The experiment grouping was as follows: naked plasmid group (P group), ultrasonic irradiation plus naked plasmid group (P-US group), naked plasmid plus CLM group (P-CLM group), naked plasmid plus ultrasound and CLM group (UTMD group). The expression of EGFP was detected by fluorescent microscopy and flow cytometry. The results showed that CLMs were spherical in shape, with the similar size and good distribution degree under the light and electron microscopies. The size of CLMs was varied from 250.4±88.3 to 399.0±99.8 nm and the Zeta potential of CLMs from 18.80±4.97 to 20.1±3.1 mV. The EGFP expression was the strongest in the UTMD group, followed by the P-CLM group, P-US group and P group. Flow cytometry results were consistent with those of fluorescent microscopy. The transfection efficiency was substantially increased in the P-US group, P-CLM group and UTMD group as compared with that in the P group, almost 7 times, 10 times and 30 times higher than that in the P group respectively. It is suggested that CLMs prepared by the method of thin film hydration are uniform in diameter, and proved non-toxic. UTMD combined with CLM can significantly increase the transfection efficiency of EGFP to targeted cells.