The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Objective To investigate the effects of remifentanil and dexmedetomidine controlled hypotension on coagulation function,cerebral oxygen metabolism and amino acid neurotransmitter levels in elderly patients undergoing orthopedic surgery.Methods The elderly patients who underwent lower extremity orthopedic surgery were divided into group A(given dexmedetomidine for hypotension),group B(given remifentanil for hypotension)and group C(given remifentanil combined with dexmedetomidine for hypotension)according to different anesthetic drugs.Systolic blood pressure(SBP),diastolic blood pressure(DBP)and heart rate(HR)were compared among the 3 groups.Cerebral oxygen metabolism[arterial oxygen content,(CaO2),oxygen saturation of internal jugular vein(SjvO2),oxygen content of internal jugular vein(CjvO2)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),plasma fibrinogen(FIB)],amino acid neurotransmitters[glutamic acid(Glu),aspartate(Asp),gamma-aminobutyric acid(GABA)]were compared,and the occurrence of adverse drug reactions during the trial were compared.Results At 12 h after anesthesia,the APTT of group A,group B and group C were(17.26±2.77),(17.37±2.92)and(31.11±4.74)s,respectively.GABA were(18.74±2.71),(19.22±2.60)and(23.37±2.59)mmol·L-1,respectively.3 min after withdrawal,CaO2 in group A,group B and group C were(139.31±9.03),(140.90±8.70)and(131.75±10.11)mL·L-1,respectively;SjvO2 were(63.59±2.23)％,(63.40±2.44)％and(68.82±3.36)％,respectively.The above indexes of group C were compared with those of group A and group B,and the differences were statistically significant(all P＜0.05).The incidence of adverse drug reactions in group A,B and C were 12.82％,27.50％and 7.32％,respectively.The incidence of adverse drug reactions in group C were lower than that in group A and group B(P＜0.05).Conclusion Remifentanil combined with dexmedetomidine for controlled hypotension in elderly orthopedic surgery has better blood pressure control effect,can improve postoperative coagulation function,maintain cerebral oxygen metabolism balance,reduce cognitive function injury and anesthesia adverse drug reactions.

Aim To explore the new mechanism of triptolide (TRI) inhibiting the progression of hepatocellular carcinoma (HCC) . Methods Different concentrations (0, 0 . 5, 2, and 8 jjunol • L~) of TRI were administered to act on liver cancer cells, and then the cell phenotypes and possible mechanisms were explored using experimental methods such as CCK-8, cell cloning, Transwell, and protein immunoblotting; siRNA was used to interfere with the target gene GSDME and its role was determined. Finally, the mechanism of TRI inhibiting the growth of HCC cells in vivo was validated using a transplanted tumor model. Results TRI could inhibit the proliferation, cloning, and invasion of HCC cells, and promote cell apoptosis. Immunoblotting results showed that the expression of GSDME was significantly upregulated in HepG2 or He-pal-6 hepatocellular carcinoma after TRI treatment, while the expression of cleaved caspase-3 and PARP also significantly increased. Knocking out GSDME could partially reverse TRI-induced cell apoptosis. At the same time, cells knocked down by GSDME had stronger cloning and migration abilities, and the apoptosis rate was reduced compared to the TRI treatment group alone. In vivo experiments showed that TRI inhibited HCC tumor growth, and the TRI + siGSDME group had a faster tumor growth rate than the TRI treatment group alone did. In addition, after TRI stimulation, p-eIF2a and ATF4 in HepG2 and Hepal-6 cells significantly increased. The immunofluorescence results showed a dose-dependent increase in the number of ATF4 positive cells in HepG2 and Hepal-6 cells after TRI stimulation. Conclusion The inhibitory effect of TRI on the growth and invasion of liver cancer cells may be related to its regulation of the ATF4/caspase-3/GSDME signaling pathway and promotion of liver cancer cell apoptosis.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

AIM To investigate the purification process for esculin,fraxin,esculetin and fraxetin in Fraxini Cortex by macroporous resin.METHODS Static adsorption experiment was applied to screening resin model,single factor test was adopted in the optimization of purification process,UPLC-QTOF-MS/MS was used for identifying main components,after which heatmap was drawn.RESULTS The optimal resin model was ADS-5.The optimal purification process was determined to be 1.1 BV for loading amount,0.75 g/mL for loading concentration,2 BV pure water for washing impurity,and 4 BV 25%ethanol for eluting effective constituents,coumarins demonstrated the total transfer rate,purity and yield of 84.42%,53.28%and 4.79%,respectively.Total 37 constituents were identified,among which coumarins and phenylethanol glycosides were mainly concentrated in 25%ethanol eluent,organic acids,iridoids and flavonoids were mainly concentrated in 95%ethanol eluent.CONCLUSION This stable,feasible and accurate method can characterize the distribution patterns of coumarins in Fraxini Cortex in different eluents of macroporous resin,which provides guidance for further related pharmaceutical research.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective:To investigate the related risk factors affecting the prognosis of hemorrhagic fever with renal syndrome(HFRS) in children.Methods:A retrospective study was carried out.We selected 182 pediatric patients who met the diagnostic criteria for pediatric HFRS while hospitalized in the Intensive Care Department of the Affiliated Children′s Hospital of Xi′an Jiaotong University between July 2014 and December 2021 as the research objects.The severe and critical patients were taken as the observation group(24 cases), and the mild and moderate pediatric patients were taken as the control group(158 cases). The demographic, epidemiological data and clinically relevant indicators within 8 hours of pediatric patients after admission were collected.The 28-day death was the primary endpoint.Renal failure and pulmonary edema were secondary endpoint.The differences of clinically relevant indicators between the two groups were observed.Logistic regression was used to analyze the risk factors and receiver operating characteristic(ROC) curve was used to determine the predictive efficacy of different outcome prediction models.Results:There were no statistically significant differences in age, gender, and BMI between the two groups (all P>0.05). Compared the control group with the observation group, coagulation function indicators such as activated partial thromboplastin time (APTT)[(134±21)s vs.(164±34)s], D-dimer [(6.31±3.20)mg/L vs.(12.43±5.67)mg/L], von Willebrand factor (vWF)[(352±45)μg/L vs.(465±103)μg/L], and platelet(PLT)[(87±35)×10 9/L vs.(45±24)×10 9/L], Lactate(Lac)[(2.6±1.1)mmol/L vs.(6.0±2.0)mmol/L]were different significantly(all P<0.05). Additionally, the lymphocyte characteristic analysis indicator lymphocytes [(2 749±686)×10 6/L vs.(2 374±851)×10 6/L], CD3 + [(1 821± 487)×10 6/L vs.(1 065±539)×10 6/L], CD4 + /CD8 + (1.65±0.73)vs.(1.00±0.25), CD19 + [(559±105)×10 6/L vs.(487± 133)×10 6/L]were different significantly(all P<0.05). The inflammatory index procalcitonin(PCT) [(22±15)ng/L vs.(56±21)ng/L, P<0.05]was different significantly in two groups.The rate of continuous renaly replacement therapy, ventilator-assisted ventilation, vasoactive drugs and other treatment measures increased significantly in observation group than those in control group(all P<0.05). Multivariate logistic regression analysis was performed on the included indicators.With death as the primary endpoint, Lac, CD8 + , D-dimer, vWF and PCT were significantly associated with mortality, which were risk factors for death, while PLT and CD4 + /CD8 + were protective factors.With renal failure and pulmonary edema as secondary endpoint, CD8 + , D-dimer, Lac and PCT were risk factors for secondary endpoint.ROC curve analysis showed that the sensitivity, specificity and AUC of the risk factor prediction model related to the primary endpoint variables were 77.91%, 81.22% and 0.769, and which related to secondary endpoint variables were 87.61%, 77.59% and 0.891, respectively. Conclusion:The combinations of CD8 + , D-dimer, Lac, PCT and vWF have good predictive value for poor prognosis in children with HFRS.

Objective:To evaluate the acute effects of different foot-strike patterns of running on knee cartilage in amateur marathon runners using the T 2* mapping technique. Methods:From November 2021 to February 2022, 29 amateur marathon runners were recruited in Hangzhou. The gait analysis was performed to determine their landing patterns, then the runners were divided into the fore-foot strike (FFS) group (11 cases) and the rear-foot strike (RFS) group (18 cases). The MRI of the knee joint of the dominant leg was performed before and 30 min after running, and the volume, thickness, and T 2* value of each division of knee cartilage were measured. Independent samples t-tests were used to compare the differences in baseline data before running between the groups, and paired samples t-tests were used to compare the differences before and after running within the groups. Results:The difference in knee cartilage volume and thickness between the FFS and RFS groups before running was not statistically significant ( P>0.05), and the T 2* value of the femur medial posterior in the RFS group was higher than that of the FFS group ( t=-2.47, P=0.020). Compared with pre-running, cartilage thickness of the tibia lateral posterior decreased in the FFS group after running ( t=-2.96, P=0.016), and cartilage thickness of the tibia lateral posterior and patella lateral central decreased in the RFS group ( t=-3.25, -3.02, P=0.004, 0.007). Cartilage volume of the tibia lateral posterior decreased in the FFS group after running ( t=-2.58, P=0.030), and the cartilage volume of the patella lateral central decreased in the RFS group ( t=-2.74, P=0.013). The differences in T 2* values of cartilage in each region before and after running were not statistically significant in the FFS group ( P>0.05), whereas in the RFS group, the cartilage T 2* values in the femur medial posterior, femoral trochanter central, femoral trochanter lateral, femur lateral central, tibia lateral anterior, tibia medial posterior, tibia medial central, and tibia medial anterior decreased ( P<0.05). Conclusions:After running, FFS showed changes in morphology and biochemical composition only in some subregions of tibial cartilage, whereas most of the femoral cartilage, patellar cartilage, and tibial cartilage regions were altered by RFS. The RFS pattern introduces greater acute changes in cartilage in the knee joint.