As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To understand how warfarin inhibition is hindered by the vitamin K epoxide reductase(VKORC1)resistant mutations.Methods An electrophoretic mobility assay was conducted based on the principle that binding with warfarin resulted in changes in VKORC1 electrophoretic mobility.The activity of VKORC1 and the half maximal inhibitory concentration(ICs0)of warfarin inhibiting VKORC1 were detected by ELISA.These experiments evaluated the binding ability of VKORC1 resistant mutants to warfarin.Results With warfarin bound,VKORC1 was protected from N-ethylmaleimide(NEM)modification and showed increased electrophoretic mobility,which was dependent on an unmodified cysteine on the flexible transmembrane helix 1(TM1)of VKORC1.In-creasing the warfarin concentration could shift more VKORC1 towards the species with the fast mobility.Compared to the wildtype VKORC1,the fast mobility fraction became less or disappeared in warfarin-resistant mutants,indi-cating weakened binding of warfarin.In addition,VKORC1 mutants with the weaker electrophoretic mobility shift indicated the stronger warfarin resistant.Conclusion Weakened warfarin binding is the primary cause of warfarin resistance.

Parkinson's disease is a neurodegenerative disease associated with abnormal copper metabolism in the brain,which leads to misfolding and aggregation of α-synuclein-copper complexes,which is an important pathological sign of Parkinson's disease.Copper metabolism,i.e.,cellular metabolic processes involving copper ions,is closely related to the pathogenesis of α-synuclein aggregation,dopamine metabolism,mitochondrial dysfunction,oxidative stress,and ferroptosis in Parkinson's disease.In this review,we summarize the molecular metabolic mechanism of copper toxicity by studying the pathological role of copper metabolism in Parkinson's disease,to support our further understanding of the mechanism of action and drug development.

Objective To investigate the differential diagnostic value of 18F-fluorodeoxyglucose(18F-FDG)/PET/CT combined with serum lactate dehydrogenase(LDH),β2-microglobulin(β2-MG),and C-reactive protein(CRP)in sarcoidosis and lymphoma.Methods The 18F-FDG PET/CT images of 19 patients with sarcoidosis and 33 patients with lymphoma were analyzed retrospectively.The lymph node maximum diameter,density,distribution morphology,maximum standardized uptake value(SUVmax),extra-nodal involvement,and serum LDH,β2-MG,and CRP results were analyzed and compared.Results There was no statistically significant difference between sarcoidosis and lymphoma in lymph node density,necrosis rate,and SUVmax(P＞0.05).There was statistically significant difference in the maximum diameter between lymph nodes in sarcoidosis(2.4±0.7)cm and lymphoma(3.3±1.3)cm(P＜0.05).The incidence of symmetric enlargement of mediastinal and hilar lymph nodes was 84.2％in sarcoidosis,the lymph node fusion rate was 21.1％,the lung involvement rate was 57.8％,the spleen involvement rate was 10.5％,and the rates of lymphoma were 15.2％,63.6％,0.0％,and 36.4％,with statistically significant differences(P＜0.05).There were statistically significant differences in LDH and β2-MG between the two groups(P＜0.05),but the differences in CRP were not statistically significant(P＞0.05).Conclusion PET/CT can show the anatomy of mediastinal and hilar lymph nodes and extra-nodal affected organs as well as glucose metabolism,showing a certain differential diagnostic value of sarcoidosis and lymphoma when combined with serum LDH and β2-MG levels.

OBJECTIVE To explore the distribution of airborne pollen in Cangzhou,to analyze the correlation between pollen characteristics,meteorological factors and the rate of allergic rhinitis visits,and to provide a reference basis for the precise prevention and treatment of allergic rhinitis in Cangzhou.METHODS The gravity deposition method was applied to collect daily airborne pollen from the monitoring sites in Cangzhou from March to October 2022 and record the pollen species and quantities.We also collected information on allergic rhinitis patients who visited the ENT Department of Cangzhou Central Hospital during the same period and meteorological data(daily maximum temperature,minimum temperature,maximum relative humidity,maximum precipitation,and maximum wind speed at ground level)during the same period,and analyzed the relationship between the number of AR patients'visits,the amount of pollen,and the meteorological factors.RESULTS 1.A total of 229 pollen exposures were collected from March to October 2022,totaling 19 368 pollen grains,of which 18 750 grains of pollen could be identified in 19 families and 618 grains were difficult to identify the families.2.There were two peaks of pollen during the period,in April and September respectively.Spring pollen to tree-based category,to the pine family,willow willow family,Xylariaceae(ash)most often;summer pollen volume has declined,but still tree-based category;fall pollen to herbaceous category,to the Asteraceae Artemisia,mulberry,Gramineae most often.3.The pollen concentration in Cangzhou City was negatively correlated with maximum humidity,maximum precipitation,maximum temperature,and minimum temperature.Maximum wind speed at ground level was positively correlated with pollen concentration.4.Pollen concentration was positively correlated with the number of visits.The correlation analysis between daily medical visits from June to October and air pollen concentration showed a significant positive correlation,while the results from March to May showed no significant correlation.CONCLUSION The peak of airborne pollen dispersal in April and September in Cangzhou.Spring and summer pollen is dominated by tree species,and the dominant pollen is Pinaceae,Willow genus of Populus,and Xylariaceae(ash genus);fall pollen is dominated by herbaceous species,and the dominant pollen is Artemisia,Asteraceae,Mulberry,and Gramineae.Meteorological factors are important factors affecting pollen concentration.Within a certain range,the lower the maximum humidity,the lowest maximum precipitation,the lower the highest or the lowest temperature,the higher the pollen concentration,and the pollen concentration is more affected by the lowest temperature.There is a correlation between pollen concentration and the number of AR patients'visits from June to October,which can be used as an environmental early warning indicator of the prevalence of AR.

Objective:To evaluate the efficacy of a modified continuous penetrating-suture pancreaticojejunostomy (PPJ), also known as a continuous PPJ with a U-shaped reinforcement of pancreatic section (U-PPJ), in patients with high risk of clinically relevant postoperative pancreatic fistula (CR-POPF).Methods:Clinical data of 33 patients with pancreatic tumors undergoing pancreatic surgery in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wannan Medical College from August 2017 to December 2023 were collected, including 22 males and 11 females, aged (64.9±8.6) years old. According to the fashion of pancreaticojejunostomy, patients were divided into two groups: U-PPJ group ( n=11) and PPJ group ( n=22). The general data, incidence of CR-POPF, abdominal bleeding and other clinicopathological data were collected. Results:All patients underwent pancreatic surgery successfully and were discharged from the hospital uneventfully. Intraoperative blood loss in U-PPJ group was 200.00 (100.0, 200.0) ml, postoperative hospitalization was 13.0 (11.0, 18.0) d, and the drain removal time was 17.0 (12.0, 21.0) d, and no CR-POPF occurred. The intraoperative blood loss, postoperative hospitalization days, drain removal time, and incidence of postoperative biochemical leakage were comparable between the groups (all P>0.05). The incidence of CR-POPF in U-PPJ group was lower than that in PPJ group [0 vs. 22.7% (5/22), P<0.05]. Conclusion:U-PPJ is safe and effective in patients with pancreatic tumors and might reduce the incidence of CR-POPF.

AIM: To investigate the implication of respiratory microbiology on the efficacy of PD-1 inhibitors monotherapy for patients with NSCLC. METHODS: This study was designed as a retrospective study, fifty-eight patients with previously-treated advanced NSCLC who were received PD-1 monotherapy from October 2018 to October 2021 were included. The PD-1 inhibitors were consisted of camrelizumab, sintilimab and pembrolizumab. Additionally, the basic demographic data, therapeutic efficacy data, survival prognosis and adverse reactions during the PD-1 inhibitors treatment were collected and analyzed through the patients' medical records of the department and the electronic medical record system of the hospital. Furthermore, deep induced sputum specimens of the patients before treatment with PD-1 inhibitor were collected. And the respiratory microbiology of 58 samples were detected using 16S rRNA gene sequencing method. The index of respiratory microbiology α diversity was analyzed, and the correlation analysis was performed with the efficacy and prognosis of patients. RESULTS: A total of 58 patients with advanced NSCLC met the study's screening criteria and were evaluable for efficacy and safety profile. Efficacy data suggested that the objective response rate (ORR) and disease control rate (DCR) of the patients who received PD-1 inhibitors was 19.0%(95% CI: 9.9%-31.4%) and 55.2% (95% CI: 41.5%-68.3%). Furthermore, prognostic data obtained from follow-up indicated that the median PFS of the 58 patients with advanced NSCLC was 3.2 months (95% CI: 2.29-4.11) and the median OS was 10.5 months (95% CI: 5.58-15.43). Regarding the exploratory analysis between efficacy and respiratory microbiology, the 58 patients with NSCLC were divided into high α diversity group (group H) and low α diversity group (group L) according to Shannon diversity index of respiratory microecology detection. And the association analysis suggested that the ORR of patients with group H and group L was 23.3% and 17.9%(P c 0.380), respectively. Furthermore, prognostic analysis indicated that the median PFS of patients with group H and group L was 3.8 and 2.8 months, respectively, which was statistically significant (P c 0.034). CONCLUSION: PD-1 inhibitors monotherapy demonstrated preliminary efficacy and prognosis as subsequent line treatment for patients with advanced NSCLC. Patients with higher α -diversity of respiratory microbiology might confer a superior prognosis. And the conclusion should be validated in large sample prospective clinical trials subsequently.

Objective:To analyze the risk factors of clinically-relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) and penetrating pancreaticojejunostomy (PPJ).Methods:The clinical data of 108 patients who underwent PD and PPJ in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Wannan Medical College from January 2017 to October 2022 were analyzed retrospectively, including 65 males and 43 females, aged 65.5 (54.2, 72.0) years. The incidences of POPF, biliary fistula, abdominal bleeding and other related complications were reviewed. The related factors of CR-POPF were analyzed by univariate analysis, and the statistically significant factors were included in multivariate logistic regression analysis.Results:A total of 108 patients were successfully treated with PD, including laparoscopic PD in 76 cases (70.4%) and open PD in 32 cases (29.6%). PPJ was performed in PD, including the continuous fashion in 39 cases (36.1%), intermittent fashion in 49 cases (45.4%) and modified continuous fashion in 20 cases (18.5%). The operation time was 390.0 (314.0, 480.0) min, the intraoperative blood loss was 200.0 (100.0, 384.0) ml, the postoperative hospital stay was 12.0 (10.0, 15.0) d, and the incidence of POPF (grade B + C) was 11.1% (12/108). Body mass index, pancreatic CT value and pancreatic duct size were the significant factors of CR-POPF (all P<0.05). Multivariate logistic regression analysis showed that age ( OR=0.895, 95% CI: 0.822-0.975), pancreatic CT value ( OR=0.812, 95% CI: 0.698-0.946) and pancreatic duct size ( OR=0.457, 95% CI: 0.220-0.952) were risk factors of CR-POPF after PPJ (all P<0.05). Conclusion:PPJ is a safe method of pancreaticoenterostomy, and CR-POPF may be related to younger patients, lower pancreatic CT value and the smaller pancreatic duct size.

Objective:To investigate the practical efficacy of low-intensity pulsed ultrasound(LIPUS)and its effects on hemodynamics in patients with coronary heart disease and angina pectoris.Methods:As a single-center randomized controlled study, 66 elderly patients with coronary heart disease and angina pectoris treated at Qilu Hospital of Shandong University between November 2021 and August 2022 were consecutively recruited.Participants were divided into an ultrasound group and a control group via the random number table method, with 33 in each group.Both groups were given conventional drug treatment, and the ultrasound group was supplemented with LIPUS treatment.After 20 sessions of treatment, the clinical efficacy, blood lipid levels, inflammatory factors and hemodynamics from noninvasive monitoring before and after treatment were compared.Results:There were no statistically significant differences in baseline data between the two groups( P>0.05). After treatment, marked effectiveness was seen in 12 cases(36.4%), effectiveness in 18 cases(54.5%), ineffectiveness in 2 cases(6.1%)and aggravation in 1 case(3%)in the ultrasound group, with a total effectiveness rate of 90.9 %.In the control group, marked effectiveness was seen 2 cases(6.1%), effectiveness in 19 cases(57.6%)and ineffectiveness in 9 cases(27.3%), with a total effectiveness rate of 63.6%.Statistically significant favorable results were achieved in the ultrasound treatment group, compared with the control group( P<0.05). Also, compared with the control group, patients in the ultrasound group showed lower total cholesterol[(2.31±1.03)mmol/L vs.(4.36±0.76)mmol/L, P<0.01], decreased low-density lipoprotein cholesterol[(1.24±0.70)mmol/L vs.(1.74±0.44)mmol/L, P<0.01], decreased triglycerides[(1.04±0.40)mmol/L vs.(1.28±0.49)mmol/L, P<0.05], decreased apolipoprotein B[(0.67±0.25)g/L vs.(0.90±0.14)g/L, P<0.01], decreased interleukin-6[(2.87±2.52)ng/L vs.(4.66±3.30)ng/L, P<0.05], and decreased high-sensitivity C-reactive protein[(1.04±1.41)mg/L vs.(3.80±5.78)mg/L, P<0.05]. Concerning hemodynamics, there was an increase in cardiac output[(4.92±1.05)L/min vs.(4.39±0.97)L/min, P<0.05], stroke volume[(75.85±17.50)ml/beat vs.(66.97±15.57)ml/beat, P<0.05], cardiac index[(37.50±7.14)ml·beat -1·m -2vs.(43.29±7.96)ml·beat -1·m -2, P<0.01], and stroke volume index[(3.05±0.45)L/min 2vs.(2.51±0.43)L/min 2, P<0.01], but a decrease in systemic vascular resistance[(1 358.29±325.23)dyne·s -1·cm -5vs.(1 617.94±526.27)dyne·s -1·cm -5, P<0.05], total vascular resistance[(4.07±24.30)% vs.(21.32±31.94)%, P<0.05], and average heart rate[(63.43±7.42)beats/min vs.(69.11±10.89)beats/min, P<0.05]. Conclusions:LIPUS treatment can improve symptoms, blood lipid profiles, inflammatory factors and hemodynamics in patients with coronary heart disease and angina pectoris.It is a safe and effective adjuvant therapy for elderly patients with coronary heart disease and angina pectoris.