Objective To investigate the ultrasonographic characteristics of acute Stanford type A aortic dissection (ATAAD) involving the renal arteries and their relationship with renal function. Methods Patients with ATAAD admitted to Deyang People's Hospital from February 2013 to May 2023 were selected for the study. Based on whether the renal arteries were involved in the dissection, the patients were divided into two groups: a renal artery involvement group and a renal artery non-involvement group. General data and ultrasound characteristics of the two groups were compared. Logistic regression analysis and model correction were performed to analyze the relationship between ultrasound characteristics and renal function involvement in ATAAD patients. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of ultrasound characteristics for renal artery involvement in ATAAD patients. Additionally, patients in the renal artery involvement group were divided into normal renal function and abnormal renal function subgroups based on serum blood urea nitrogen (BUN) and serum creatinine (Scr) levels. Clinical data of the two subgroups were compared, and a log-binomial model was used to analyze the risk effects of ultrasound characteristics for abnormal renal function. Pearson correlation analysis was performed to assess the correlation between ultrasound characteristics of renal artery involvement and renal function indicators. Results A total of 163 patients were included, consisting of 106 males and 57 females, with a mean age of (50.06±10.46) years (ranging from 20 to 85 years). Significant differences in gender, Scr, and BUN were observed between the renal artery involvement group and the renal artery non-involvement group (P<0.001). Compared to the renal artery non-involvement group, the renal artery involvement group had an increased ascending aorta diameter, a greater proportion of ascending aortic dilation and poor renal perfusion (P<0.05). Logistic regression analysis indicated that ascending aorta diameter, ascending aortic dilation, and poor renal perfusion were independent factors for renal artery involvement (P<0.05). Ultrasonographic characteristics showed good predictive ability for renal artery involvement in ATAAD patients. Furthermore, the combination of the three characteristics yielded a higher predictive value for renal artery involvement. Compared to the normal renal function group, the abnormal renal function group had higher BUN and Scr levels, increased ascending aortic diameter, a greater proportion of ascending aortic dilation and poor renal perfusion (P<0.05). The log-binomial model analysis revealed that the risk ratios for ascending aortic diameter, ascending aortic dilation, and poor renal perfusion were statistically significant both before and after adjustment (P<0.05). Pearson correlation analysis revealed that ascending aortic diameter, ascending aortic dilation, and poor renal perfusion were strongly correlated with renal function parameters (P<0.05). Conclusion Ultrasound characteristics of ATAAD involving the renal arteries are associated with renal function. Ascending aorta diameter, ascending aortic dilation, and poor renal perfusion are independent risk factors for abnormal renal function.

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P＜0.01),and the E2 level was significantly decreased(P＜0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P＞0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P＜0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P＜0.05),had no difference with the blank group(P＞0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P＜0.01),still being lower than the blank group(P＜0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P＞0.05),while the protein expression level of P450arom was lower than that in the model group(P＜0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P＜0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P＜0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P＜0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P＜0.05 or P＜0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.

Objective:With the in-depth study of complement dysregulation,glomerulonephritis with dominant C3 has received increasing attention,with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types.This study analyzes the clinical,pathological,and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3,aiming to avoid misdiagnosis and missed diagnoses. Methods:The clinical,pathological,and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed.According to the clinical feature and results of pathology,15 patients with post-infectious glomerulonephritis(PIGN)and 37 patients with of non-infectious glomerulonephritis(N-PIGN)were classified.N-PIGN subgroup analysis was performed,and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group,or 27 in a C3 glomerulopathy(C3G)group and 10 in a non-C3 nephropathy(N-C3G)group. Results:The PIGN group had lower creatinine values(84.60 μmol/L vs 179.62 μmol/L,P= 0.001),lower complement C3 values(0.36 g/L vs 0.74 g/L,P<0.001)at biopsy,and less severe pathological chronic lesions compared with the N-PIGN group.In the N-PIGN subgroup analysis,the C3-dominant-deposition group had higher creatinine values(235.30 μmol/L vs 106.70 μmol/L,P=0.004)and higher 24-hour urine protein values(4 025.62 mg vs 1 981.11 mg,P=0.037)than the C3-alone-deposition group.The prognosis of kidney in the PIGN group(P=0.049),the C3-alone-deposition group(P=0.017),and the C3G group(P=0.018)was better than that in the N-PIGN group,the C3-dominant-deposition group,and the N-C3G group,respectively. Conclusion:Glomerulonephritis with dominant C3 covers a variety of pathological types,and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G;in addition,the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis,and relevant diagnosis,treatment,and follow-up should be strengthened.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective To evaluate the safety,tolerability and pharmacokinetic profiles of naldemedine in Chinese healthy adult subjects after single and multiple administrations.Methods After single and multiple oral administrations of naldemedine to 10 healthy Chinese subjects,the plasma concentrations of naldemedine and its metabolite(nor-naldemedine)were measured by liquid chromatography-mass spectrometry,and the pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.3.1 software.Results Compared with single administration,naldemedine showed no significant change in the tmax(1.06 h for single and 1.08 h for multiple)and Cmax(4.16 ng·mL-1 for single and 4.11 ng·mL-1 for multiple),higher AUC0-τ than that of single(23.88 ng·h·mL-1 for single and 28.93 ng·h·mL-1 for multiple),slightly prolonged t1/2(9.26 h for single,12.50 h for multiple),there was a slight drug accumulation after multiple doses(accumulation ratio of 0.99 for Cmax and 1.22 for AUC);t1/2(18.10 h for single,29.30 h for multiple),Cmax(0.19 ng·mL-1 for single,0.38 ng·mL-1 for multiple),and AUC0-τ(3.13 ng·h·mL-1 for single,6.02 ng·h·mL-1 for multiple)were all significantly elevated with nor-naldemedine,and the tmax(single was 3.49 h and multiple was 3.56 h)did not change significantly.The Cmax ratio and AUC ratio of metabolites to naldemedine were significantly elevated,and accumulation was present after multiple administrations(accumulation ratio of 2.01 for Cmax and 1.95 for AUC).All adverse events that occurred after treatment were mild.Conclusion After multiple oral administrations of 0.2 mg naldemedine tablets to Chinese healthy subjects(single dose on day 1 and once daily on days 4-13),the drug was eliminated rapidly with mild accumulation,and reached a steady state before the second dose of the multiple-dosing phase,and the product has a favorable safety and tolerability profiles.

Objective To establish an ultra-high performance liquid phase tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma and to study its pharmacokinetics.Methods The plasma samples were precipitated by acetonitrile vortex,centrifuged,dried by nitrogen,dissolved by mobile phase,and then analyzed.Chromatographic column:Shiseido CAPCELL PAK CR(1∶4)column(2.0 mm × 150.0 mm,5 μm),temperature:25 ℃.Mobile phase:Acetonitrile:0.1％formic acid solution(containing 10 mmoL·L-1 ammonium formate)(73∶27)with flow rate:0.3 mL·min-1 and injection volume was 2 μL.The electrospray ion source ionization and positive ion multiple reaction monitoring mode were used for mass spectrometry detection,and biological sample methodology verification was carried out according to requirements.After intragastric administration with 5 mg·kg-1 dose of L-synephrine,blood samples were collected at different time points to investigate the pharmacokinetic characteristics of L-synephrine in rats.Results L-synephrine showed a good linear relationship in the range of 2-800 ng·mL-1,the lowest limit of quantification of L-synephrine was 2 ng·mL-1.Precision,extraction recovery,matrix effect,accuracy,dilution effect and residual effect all meet the requirements all met the requirements.The main pharmacokinetic parameters:Cmax were(464.83±76.68)ng·L-1,tmax were(0.67±0.26)h,t1/2z were(1.89±0.48)h,AUC0-t were(602.26±42.25)ng·mL-1·h-1,AUC0-∞ were(612.28±41.18)ng·mL-1·h-1.Conclusion The established ultra high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma is simple and rapid,and can be used for the determination of L-synephrine in plasma.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.