The paper introduces Professor SUN Shentian's experience in clinical practice of Ningshen (tranquilizing the mind) point. This point is an empirical point discovered by Professor SUN on the basis of meridian differentiation, nerve function and anatomic location, and in association with the years of clinical practice. The point is located in the prefrontal area, jointed with the distribution of the governor vessel, and responded to the body surface projection area of the frontal pole. It works on regulating the mind, regaining consciousness, improving cognition, alleviating depression, mutually treating physical and mental disorders, as well as unblocking collaterals, regulating the tendons and relieving spasm. This point is widely used in treatment of mental disorders, stroke and extrapyramidal diseases and obtains the reliable therapeutic effect in clinical practice.
Humans ; Acupuncture Points ; Acupuncture Therapy/history* ; China ; Meridians ; History, 20th Century

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

To implement the strategy of healthy China and promote the construction of "new medicine science", it is urgent to focus on new needs and challenges to advance the reform of medical education curricula in China. Using literature research methods, we summarize the process of modern medical education curriculum reforms in the United States, and discuss the main features of the third-round reforms—introducing the concept of value-based medicine, offering health systems science courses, and promoting the curriculum system reform from the perspectives of learning time, curriculum integration, and learning methods. Based on these features, we put forward the enlightenment for the reform of medical education curricula in China.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.

Objective To investigate the efficacy and safety of subretinal fluid extraction combined with intravitreal conbercept and gas injection in treating polypoidal choroidal vasculopathy(PCV)complicated with serous retinal pigment epithelium detachment(sPED).Methods From July 2019 to February 2021,13 patients(13 eyes)with PCV complicated with sPED who were treated with subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the Weifang Eye Hospital were selected.All affected eyes received at least 3 times(once a month)of intravitreal anti-vas-cular endothelial growth factor(VEGF)(ranibizumab)injections before the surgery,and the treatment was ineffective.The changes in best corrected visual acuity(BCVA),central retinal thickness(CRT),macular foveal PED height and width before and 1 week,1 month,3 months and 6 months after the operation were observed,and the intraoperative and postop-erative complications were recorded.Results The BCVA of the affected eyes 1 week after operation was better than that before operation,and the difference was statistically significant(Z=-3.237,P=0.001).The CRT of the affected eyes at 1 week,1 month,3 months and 6 months after the operation were thinner than that before the operation,and the differ-ence was statistically significant(Z=-3.180,-3.180,-3.110 and-3.180,P=0.001,0.001,0.002 and 0.001).The height and width of PED at 1 week,1 month,3 months and 6 months after the operation were lower than those before the operation,and the differences were statistically significant(all P＜0.05).Thirteen eyes received an average of(4.15±1.40)intravitreal injections(ranibizumab)before the surgery,and the treatment duration was(5.92±3.95)months(equivalent to one injection every 6 weeks).During the 6-month follow-up,13 eyes received an average of(2.31±1.97)intravitreal injections(conbercept)(equivalent to once every 10 weeks).Partial correlation analysis showed a weak positive correla-tion between the increase in BCVA and the decrease in CRT 6 months after operation(r=0.416,P=0.203).There was no significant correlation between the increase in BCVA and the changes in PED height and width 6 months after operation(r=0.218,0.209,P=0.520,0.538).At 1 month after the operation,9 eyes had PED recurrence or different degrees of retinal nerve subepithelial effusion,and PED improved after repeated intravitreal injection of conbercept.At 6 months after opera-tion,subfoveal PED completely disappeared in 3 eyes,and the retina was completely reattached.There was still active exu-dation in the retina of 1 eye.No systemic or severe ocular complications occurred in 13 eyes during the follow-up period.Conclusion Subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the treatment of PCV complicated with sPED can safely and effectively reduce CRT,improve PED,and reduce the damage to the retina caused by long-term PED,but it has no significant effect on the improvement of BCVA at 6 months after the operation.

Objective:To explore the practical value of general anesthesia with non-intubated spontaneous breathing in uniportal thoracoscopic surgery in elderly patients.Methods:Clinical data of 86 elderly patients undergone uniportal thoracoscopy surgery during hospitalization at our hospital between March 2020 and December 2021 were retrospectively reviewed and analyzed.Based on the anesthesia intubation method, they were divided into a non-intubated spontaneous breathing video-assisted thoracic surgery group(NI-VATS group)and a one-lung ventilation video-assisted thoracic surgery group(OLV-VATS group), with 43 cases in each group.Data were compared on the inflammatory indexes, preparation time for anesthesia, time to awakening after anesthesia, intraoperative lung collapse score, mediastinal flutter score, time to postoperative feeding, digestive tract complications, sore throat, postoperative pulmonary atelectasis, and hospitalization time.Results:Compared with the OLV-VATS group, the NI-VATS group had a shorter anesthesia preparation time [(19.8±2.6)min vs.(32.3±4.5)min, t=-15.77, P<0.001]and a shorter time to awakening [(6.8±2.1)min vs.(11.9±2.9)min, t=-9.485, P<0.001], slightly poorer operating field during surgery, an unfavorable lung collapse score [(2.5±0.7) vs.(1.8±0.7) t=4.704, P<0.001], worse mediastinal flutter [(2.1±0.6) vs.(1.3±0.5), t=6.514, P<0.001]. Lower procalcitonin(PCT)[(0.189±0.130)μg/L vs.(0.264±0.123)μg/L, t=-2.744, P=0.007), a shorter time to postoperative feeding [(3.4±1.0)h vs.(5.5±1.0)h, t=-9.55, P<0.001], and lower rates of digestive tract reactions(4.7% vs.20.9%, χ2=5.108, P=0.024)and throat pain(4.7% vs.23.3%, χ2=6.198, P=0.013), and a shorter length of hospital stay [(3.8±0.3)d vs.(4.9±0.8)d, t=-7.266, P<0.001]. Conclusions:For the elderly patients undergoing uniportal thoracoscopic surgery, non-intubated spontaneous breathing may somewhat obstruct the operating field, but it can shorten the time of anesthesia and the time to awakening, does not increase complications from anesthesia and surgery, favors rapid postoperative recovery for patients and therefore should be promoted.

Objective:To compare the efficacy and safety of intravitreal injection of anti-vascular endothelial growth factor drug conbercept and intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema (DME).Methods:A randomized controlled clinical study was performed.Thirty-six DME patients (36 eyes) were enrolled in Weifang Eye Hospital from March 2018 to June 2019.The patients were randomized into Ozurdex group and conbercept group via a random number table, with 18 eyes in each group.Patients received Ozurdex injection once, which was maintained for 6 months, or conbercept injection once a month for 3 times according to grouping.Before and after treatment, the best corrected visual acuity (BCVA) was examined with the International Standard Visual acuity chart and converted to logarithm of minimal angle resolution unit.The intraocular pressure (IOP) was measured using a non-contact tonometer.The central retinal thickness (CRT) was detected by optical coherence tomography (OCT).This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Weifang Eye Hospital.Results:All patients were followed up for 6 months.In Ozurdex group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection was 0.59±0.22, 0.53±0.20, 0.41±0.16, 0.38±0.19 and 0.56±0.19, respectively.The BCVA at 1 month, 3 and 4 months after the first injection were better than that before injection, and the differences were statistically significant (all at P<0.05).In conbercept group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection were 0.60±0.23, 0.51±0.17, 0.29±0.13, 0.56±0.18 and 0.60±0.18, respectively.The BCVA at 1 month and 3 months after the first injection were better than that before injection, showing statistically significant differences (all at P<0.05).The CRT at 1 month, 3 and 4 months after the first injection were significantly lower than that before treatment in both the two groups (all at P<0.05).The CRT pre-injection was (498.61±77.14)μm in Ozurdex group, which was significantly higher than (462.17±48.74)μm at 6 months after the first injection ( P<0.05).No significant difference in CRT was found between pre-injection and 6 months after the first injection in conbercept group ( P>0.05).The incidence of high IOP in Ozurdex group was 33.3%(6/18), which was higher than 5.56%(1/18) in conbercept group, with a significant difference ( χ2=4.433, P=0.035).No adverse effects such as aggravation of cataract, lens injury, endophthalmitis, vitreous hemorrhage and retinal detachment was found during the follow-up. Conclusions:For DME, both conbercept and Ozurdex can improve BCVA and reduce CRT.Ozurdex shows durable efficacy and needs fewer injections than conbercept, but conbercept has less effect on IOP and is safer than Ozurdex.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

Objective:To observe the effect of non-vitrectomy in the treatment of idiopathic macular epiretinal membranes (IMEM).Methods:This study is a randomized controlled trial. From December 2017 to December 2018, 60 IMEM patients (60 eyes) diagnosed in Weifang Eye Hospital were included in the study. BCVA, intraocular pressure (IOP) and OCT were performed in all patients. The BCVA examination was performed using the international standard visual acuity chart, which was converted to logMAR. The CMT was measured by OCT. According to the surgical methods, the patients were divided into non-vitrectomy group and control group, 30 patients (30 eyes) in each group. The age ( t=1.723), logMAR BCVA ( t=1.703), CMT ( t=-0.956), IOP ( t=-1.434) were not significantly different between the two groups ( P=0.090, 0.094, 0.343, 0.157). 23G vitreous cutting system was used in all eyes. The macular epiretinal membranes was removed by non-vitrectomy in the non-vitrectomy group and by vitrectomy in the control group. The relevant examination with the same equipment and methods before the operation at 1 week and 1, 3, 6 months after operation. The time of surgery, the changes of BCVA, CMT and postoperative complications in the two groups were observed comparatively. Variance analysis of repeated measurements was performed for the comparison of BCVA, CMT and IOP after surgery in the two groups. Wilcoxon rank sum test of two independent samples was performed for the degree of vision improvement. The incidence of postoperative complications was compared by χ2 test. Results:At 6 months after operation, BCVA increased in 24 eyes (80%) and unchanged in 6 eyes (20%) in the non-vitrectomy group. Compared with preoperative BCVA, the difference was statistically significant ( P<0.05). BCVA increased in 25 eyes (83.4%), unchanged in 4 eyes (13.3%) and decreased in 1 eye (3.3%) in the control group. Compared with preoperative BCVA, the difference was statistically significant ( P<0.05). There was no significant difference between the two groups in BCVA improvement degree after operation ( Z=-0.26, P>0.05). At 6 months after operation, the average logMAR BCVA was statistically significant compared with the preoperative in the non-vitrectomy group ( P=0.002, 0.005) and control group ( P=0.004, <0.001). Visual stability occurred 1 month after operation in the non-vitrectomy group and 3 months after operation in the control group. The effective operative time of the non-vitrectomy group and control group was 4.50±1.41 and 15.50±2.33 min, respectively. The difference of effective operation time between the two groups was statistically significant ( t=-22.12, P <0.05). After surgery, no significant complications were found in the non-vitrectomy group. In the control group, there were 3 eyes with low IOP and 1 eye with macular hole during operation. Conclusions:Non-vitrectomy and vitrectomy have similar effects on IMEM. Non-vitrectomy has short effective operation time, faster recovery after surgery and no obvious complications.

Objective To investigate the effect of EP4 gene silencing on the growth and migration of K1 cells. Methods K1 cells with stable knockdown of EP4 were constructed with lentiviral vector. QRT-PCR and western blot analysis were used to detect the expression of EP4 mRNA and protein in K1 cells. CCK8 assay and flow cytometry were employed to measure cell viability and apoptosis. Transwell assay was applied to detect cell migration. Results Compared with the negative control group,the mRNA and protein expression of EP4 were sig-nificantly decreased in K1 cells with stable knockdown of EP4. Furthermore,shRNA-mediated silencing of EP4 gene remarkably suppressed cell viability and induced apoptosis of K1 cells.The migration of K1 cells with knock-down of EP4 was decreased compared with the negative control group. Conclusions EP4 gene silencing can in-hibit growth and induce apoptosis of K1 cells.Downregulation of EP4 can significantly reduce migration of K1 cells.