ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

BACKGROUND:The mechanisms underlying the occurrence of pressure injuries are complex,and it is not entirely clear which factors play a central role in the development of pressure injuries and how these factors operate. OBJECTIVE:To investigate the relationship between Piezo-type mechanosensitive ion channel component 1(Piezo1)and the occurrence of pressure injuries. METHODS:(1)Cellular experiment:Human immortalized keratinocytes(HaCaT)were treated with Yoda1,a Piezo1 agonist,at different concentrations.Cell viability,calcium ion influx,Piezo1,and apoptosis-related protein expression were detected.(2)Animal experiment:Twelve Sprague-Dawley rats were randomly divided into a control group and three experimental groups,with three rats in each group.The control group was not subjected to pressure,while in the three experimental groups,magnets with a thickness of 1,2,and 3 mm were used to press on both sides of the rats'back for 1 hour,respectively,to establish the animal models of pressure injuries.After modeling,all traumatic tissues were excised and subjected to hematoxylin-eosin,Masson,immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:Cellular experiments:The results of live/dead cell staining showed that HaCaT cell apoptosis increased with the increase of Yoda1 concentration(0,2.5,5,and 10 μmol/L),and calcium ion influx increased with the increase of Yoda1 concentration(0,5,and 10 μmol/L),as well as with the prolongation of treatment time.Western blot assay results showed an increase in the expression of BAX,TG2,and PIEZO1 and a decrease in the expression of the expression of Bcl-2 protein in HaCaT cells in 5 and 10 μmol/L Yoda1 groups compared with the control group(0 μmol/L Yoda1).Animal experiments:The results of hematoxylin-eosin and Masson staining showed that the skin structure of the three experimental groups was damaged at the compression site,there was subcutaneous fat liquefaction and necrosis,and collagen was sparse and disorganized,and damage to the skin structure at the compression site was aggravated with the increase of magnet thickness.Immunofluorescence staining and western blot results showed that compared with the control group,the expression of BAX,TG2,Yap1 and PIEZO1 proteins was elevated,and the expression of Bcl-2 proteins was lowered in the three experimental groups.Moreover,the expression of related proteins showed more significant changes with the increase of magnet thickness(pressure).To conclude,skin compression activates PIEZO1,leading to a significant influx of calcium ions.As the pressure increases,this ultimately results in cell apoptosis due to calcium overload.

OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform， and to evaluate the effectiveness of the reform， thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis， the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment， training， assessment， and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency， with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform， the new training system and model became increasingly mature. In both 2023 and 2024， the participants achieved relatively high average total scores in their initial completion assessments [with scores of （84.05± 5.83） and （85.82±4.35） points， respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of （4.80±0.44） and （4.85±0.39） points， respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future， clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase， while aligning with global trends in pharmacy education and industry development. Additionally， sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.

Objective:To investigate the clinicopathological characteristics of early gastric cancer with mixed histological staging, and to analyze the prognostic effect of endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Clinical data of early gastric cancer patients treated with ESD in Gansu Wuwei Cancer Hospital from January 2011 to March 2020 were collected, and clinicopathological characteristics of patients with mixed-type early gastric cancer were analyzed by descriptive statistical methods. The clinical effects and influencing factors of ESD on early gastric cancer were analyzed by logistic regression. Kaplan-Meier was used to estimate the survival rate, and log-rank test was used to compare the survival rate.Results:A total of 269 patients (280 lesions) were included in this study, including 216 males (80.30%) and 53 females (19.70%), with age of 60.43±8.01 years. There were 25 lesions (8.93%) of mixed early gastric cancer, 248 lesions (88.57%) of differentiated early gastric cancer, and 7 lesions (2.50%) of undifferentiated early gastric cancer. Compared with differentiated and undifferentiated early gastric cancer, the lesion site of mixed early gastric cancer was mainly located in the upper 1/3 of the stomach [64.00% (16/25), 40.73% (101/248) VS 0.00% (0/7), χ2=10.211, P=0.006], the proportion of the lesion size ≤2 cm was relatively small [52.00% (13/25), 80.65% (200/248) VS 85.71% (6/7), χ2=11.173, P=0.004], and the proportion of infiltration depth in the mucosa was lower [52.00% (13/25), 85.48% (212/248) VS 57.14% (4/7), χ2=20.019, P<0.001], the proportion of positive vertical resection margin was relatively high [20.00% (5/25), 2.82% (7/248) VS 0.00% (0/7), χ2=16.657, P<0.001], the proportion of vascular invasion was higher than that of differentiated carcinoma but lower than that of undifferentiated carcinoma [36.00% (9/25), 2.42% (6/248) VS 42.86% (3/7), χ2=58.413, P<0.001], the complete resection rate was lower [76.00% (19/25), 93.15% (231/248) VS 100.00% (7/7), χ2=9.497, P=0.009], the curative resection rate was lower than that of differentiated early gastric cancer, but higher than that of undifferentiated early gastric cancer [48.00% (12/25), 89.52% (222/248) VS 42.86% (3/7), χ2=39.757, P<0.001], and the proportion of eCura grade C2 was higher than that of differentiated cancer, but lower than that of undifferentiated cancer [48.00% (12/25), 5.65% (14/248) VS 57.14% (4/7), χ2=58.766, P<0.001]. The results of multivariate analysis showed that the larger lesions ( P=0.004, OR=0.539, 95% CI: 0.354-0.822) was the risk factor for curative resection. In terms of infiltration depth, mucosal ( P=0.001, OR=51.799, 95% CI: 5.535-84.768) and submucosal 1 ( P<0.001, OR=29.301, 95% CI: 24.694-73.972) were protective factors for curative resection compared with submucosal 2. In terms of differentiation degree, compared with mixed type, differentiated type ( P=0.024, OR=3.947, 95% CI: 1.195-13.032) was the protective factor for curative resection, while undifferentiated type ( P=0.443, OR=0.424, 95% CI: 0.048-3.788) showed no difference between curative resection and mixed type. During the follow-up, 7 patients died. The overall survival time was 114.42±0.97 months, and the 5-year survival rate was 97.10%. There was no significant difference in the survival rate of early gastric cancer patients with different degrees of differentiation ( χ2=0.434, P=0.805). The survival rate of early gastric cancer patients with or without curative resection was significantly different ( χ2=4.081, P=0.043). Conclusion:Mixed early gastric cancer patients show high margin positive rate, vascular infiltration, and less curative resection than differentiated early gastric cancer. Therefore, the process of treating mixed early gastric cancer should be more rigorous. The long-term survival prognosis of early gastric cancer after ESD treatment is promising.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

OBJECTIVE To observe the clinical efficacy of Yangyin Jiedu Decoction in the prevention and treatment of acute ra-diation-induced oral mucositis(RTOM).METHODS A total of 80 inpatients who were diagnosed with head and neck tumors by pathological examination and received radiotherapy in the Department of Radiotherapy,Affiliated Hospital of Nanjing University of Chi-nese Medicine from November 2021 to September 2023 were selected and randomly divided into an observation group and a control group with 40 cases in each group.The control group was given mouthwash treatment from the onset of RTOM symptoms until the symp-toms disappeared;the observation group was given Yangyin Jiedu Decoction from the first day of radiotherapy on the basis of the treat-ment of the control group until the end of radiotherapy.During the treatment,the onset time,duration and incidence of grade Ⅱ-ⅣRTOM in the two groups were observed;the pain numerical rating scale(NRS)score,Karnofsky performance status(KPS)score,body mass index(BMI)changes were evaluated;and the levels of serum inflammatory factors[C-reactive protein(CRP),interleukin 6(IL-6),interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)]were detected.RESULTS After radiotherapy,RTOM ap-peared in both groups to varying degrees.The incidence of grade Ⅱ-Ⅳ RTOM,the onset time,duration and NRS score of RTOM in the observation group were significantly better than those in the control group(P<0.05,P<0.01).After radiotherapy,the levels of se-rum CRP,IL-6,IL-1β and TNF-α in the observation group were lower than those in the control group(P<0.05,P<0.01).After radiotherapy and 1 month of follow-up,the KPS score and BMI in the observation group were higher than those in the control group(P<0.05,P<0.01).CONCLUSION Yangyin Jiedu Decoction can decrease the incidence and severity of RTOM in patients with head and neck tumors,shorten its duration,improve the quality of life of patients,downregulate the level of inflammatory cytokines,and has a preventive effect on RTOM caused by radiotherapy in patients with head and neck tumors.

Objective:To explore the clinical efficacy of small incision floating line drainage for the treatment of high perianal abscess.Methods:A retrospective analysis was conducted on the clinical data of 95 patients with high perianal abscess treated at the Medical Community General Hospital of Shaoxing Central Hospital from April 2019 to April 2021. Among them, 47 cases were treated with small incision floating line drainage (experimental group), and 48 cases were treated with conventional multi incision drainage (control group). The surgical time, intraoperative bleeding, postoperative pain, urination status, anal function evaluation, wound healing status and the clinical efficacy of the patient after 2 months of treatment were compared between the two groups.Results:The surgical time, intraoperative bleeding volume in the experimental group were lower than those in the control group: (18.70 ± 0.48) min vs. (38.10 ± 2.52) min, (32.35 ± 3.56) ml vs. (51.56 ± 6.24) ml, there were statistical differences ( P<0.05). The postoperative pain, urination status, anal function evaluation in the experimental group were better than those in the control group. In the experimental group, multiple incision drainage had a greater impact on patients and the wound healing cycle was longer. After treatment for 2 months, the total effective rate in the experimental group was better than that in the control group: 100.00%(47/47) vs. 91.67%(44/48), there was statistical difference ( χ2 = 4.09, P<0.05). Conclusions:Patients with high perianal abscess and treated with small incision floating line drainage has a shorter wound healing cycle, less pain, lower anal damage, and better clinical efficacy.