OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

Objective To investigate the molecular mechanism of tetramethylpyrazine(TMP)in the treatment of acute myocardial infarction(AMI).Methods SD rats were randomly divided into sham group(only threading without ligation),AMI(ligation of left anterior descending coronary artery),AMI+TMP(20 mg·kg-1 TMP),AMI+TMP+miR-155-5p(20 mg·kg-1 TMP+miR-155-5p 200 μL),AMI+TMP+miR-155-5p+ACTA1 group(20 mg·kg-1 TMP+miR-155-5p and ACTA1 200 μL).The cardiac function of rats was detected by ultrasound.The expression of cardiac troponin Ⅰ(cTn Ⅰ)was detected by immunohistochemistry.Creatine kinase MB(CK-MB)was detected by enzyme-linked immunosorbent assay(ELISA).Terminal deoxynucleotidyl transferase-mediated nick end labeling(Tunel)assay was used to detect the apoptosis rate of cardiomyocytes.The levels of miR-155-5p and ACTA1 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The expression levels of cTn Ⅰ in sham group,AMI,AMI+TMP,AMI+TMP+miR-155-5p,AMI+TMP+miR-155-5p+ACTA1 group were 1.04±0.21,13.63±1.92,7.88±2.23,11.96±3.02,8.34±1.88;the expression levels of miR-155-5p were 1.03±0.21,3.67±0.56,1.85±0.43,3.12±0.66,1.92±0.64,respectively;CK-MB levels were(37.03±7.98),(163.39±20.04),(77.63±15.77),(147.98±11.30),(80.56±10.39)U·L-1,respectively;the above indexes were compared between AMI+TMP group and AMI group,AMI+TMP+miR-155-5p group and AMI+TMP group,AMI+TMP+miR-155-5p+ACTA1 group and AMI+TMP+miR-155-5p group,and the differences were statistically significant(all P＜0.05).Conclusion TMP may inhibit apoptosis,reduce inflammation and myocardial fibrosis through miR-155-5p/ACTA1 molecular axis,and improve myocardial injury in AMI.

Objective:To evaluate the diagnostic value of rapid on-site evaluation (ROSE) performed by endoscopists for solid pancreatic lesions requiring tissue for immunohistochemistry (IHC) staining with different approach of endoscopic ultrasound-guided tissue acquisition (EUS-TA).Methods:After screening 1 573 cases who underwent EUS-TA operation at the Endoscopy Center of Peking Union Medical College Hospital between August 2018 and October 2022, a total of 65 cases of solid pancreatic lesions whose diagnosis rely on IHC staining was collected and summarized with clinical data of each case. Among 65 cases, there were 46 cases of pancreatic neuroendocrine tumors (PNETs), 13 cases of pancreatic solid pseudo-papillary tumors (SPTs), and 6 cases of lymphomas and mesenchymal. Patients were categorized into ROSE group (36 cases) and non-ROSE group (29 cases) according to the presence or absence of endoscopists performed ROSE during EUS-TA operation. They were further divided into subgroups of FNA-ROSE (26 cases), FNB-ROSE (10 cases), FNA-non-ROSE (24 cases) and FNB-non-ROSE (5 cases) according to the type of EUS-TA. Diagnostic accuracy and IHC success rate were compared between different groups and subgroups. Binomial logistic multifactorial regression analysis was used to evaluate the influence of ROSE and EUS-TA type on diagnostic accuracy and IHC success rate.Results:There were no statistically significant differences between ROSE group and non-ROSE group in terms of age, gender, bilirubin level, CA19-9 level, lesion site, lesion size, composition ratio of diagnosis, and surgical rate. The differences in mean size of lesions, needle gauge, location of puncturation, and number of needle pass between subgroups were not statistically significant. The diagnostic accuracy was 88.9% in ROSE group and 79.3% in non-ROSE group, and the difference between the two groups was statistically significant ( P=0.023). The diagnostic accuracy of FNA-ROSE group was higher than that of FNA-non-ROSE group (88.5% vs 75.0%), but the difference was not statistically significant ( P>0.100). The differences in diagnostic accuracy and success rate of IHC between FNB-ROSE group and FNB-non-ROSE group were not statistically significant. Binomial logistic multifactorial regression analysis did not reveal any independent influences on diagnostic accuracy. Conclusions:ROSE performed by endoscopists improved diagnostic accuracy of EUS-TA in solid pancreatic lesions requiring IHC staining, and therefore is potentially valuable for improving the diagnostic efficiency of EUS-TA for such diseases.

To promote the construction of a wound repair and regeneration system with Chinese characteristics, it is necessary to follow the principle of combining traditional Chinese and Western medicine, and integrate theory, clinical practice, and teaching. Traditional Chinese medicine emphasizes a holistic concept and the principle of dialectical treatment, while Western medicine focuses on etiological analysis and local treatment. The combination of Chinese and Western medicine can complement each other's advantages and improve treatment effectiveness. The key technological innovations in repairing and regenerating systems cover areas such as drug therapy, physical therapy, and the application of biomaterials. This article discusses the development potential and challenges of combining traditional Chinese and Western medicine in the field of wound repair and regeneration, providing new ideas and methods for the development of wound repair and regeneration. It is expected to bring better medical services and treatment effects to patients undergoing repair and regeneration.

Objective:To investigate the efficacy and safety of mini-track,mini-nephroscopy and mini-ultrasonic probe percutaneous nephrolithotomy(3mPCNL)for the treatment of 1.5-2.5 cm kidney stones.Methods:The perioperative data and postoperative follow-up data of a total of 25 patients with about 1.5-2.5 cm kidney stones who underwent 3mPCNL under ultrasound guidance in Peking Univer-sity People's Hospital from November 2023 to January 2024 were retrospectively analyzed.During the matching period,the 25 patients with 1.5-2.5 cm kidney stones receiving standard percutaneous neph-rolithotomy(sPCNL)were matched one-to-one according to the criterion that the absolute difference of the maximum diameter of stones between the two groups was less than 1 mm.The operative time,renal function changes,postoperative stone-free rate,hemoglobin changes,and complication rate of the two treatments were compared,and then the effectiveness and safety of 3mPCNL were preliminarily analyzed.Results:There were no significant differences in mean age,preoperative median creatinine,preoperative mean hemoglobin,preoperative mean hematocrit,median stone maximum diameter,and median stone CT density between the 3mPCNL group and the sPCNL group.The median operation time in the 3mPCNL group was 60.0(45.0-110.0)min,with no statistical significance compared with the sPCNL group,and all the patients underwent single-channel operations.The mean hemoglobin after operation in the 3mPCNL group was(115.3±15.5)mmol/L,and there was no significant difference between the preoperative group and the sPCNL group,and the mean hemoglobin decreased significantly between the sPCNL group and the sPCNL group[(9.5±2.2)mmol/L vs.(10.1±1.9)mmol/L].The mean hematocrit after operation was(28.0±5.2)％,and the difference was statistically significant compared with that before operation(t=2.414,P=0.020).The mean hematocrit drop was not statistically signi-ficant compared with the sPCNL group(2.3％vs.2.7％).The median serum creatinine in the 3mPCNL group was 74.0(51.0-118.0)μmol/L after operation,and the difference was statistically significant compared with that before operation(Z=-2.980,P=0.005).The stone-free rate in the 3mPCNL group and the sPCNL group was 96.0％and 97.3％,respectively,and the mean hospital stay was(4.3±1.4)d and(5.5±2.0)d,respectively,with the statistical significance(t=0.192,P=0.025).After the operation,one patient in sPCNL group had massive hemorrhage after the nephrostomy tube was re-moved,which was improved after selective renal artery embolization.One patient in the 3mPCNL group developed mild perirenal hematoma,which was improved after conservative treatment,and no complica-tions were observed in the other patients.Conclusion:3mPCNL in the treatment of 1.5-2.5 cm kidney stones can achieve an effective rate comparable to sPCNL,and can achieve the ideal stone-free rate in a shorter operative time with a lower rate of surgery-related complications.

Purpose To investigate the clinical pathologic features of five SMARCA4-deficient non-small lung cancers(SMARCA4-dNSCLCs).Methods Five cases of SMARCA4-dNSCLC was underwent by HE,immunohistochemical staining,and molecular detection,analyzed their clinicopathological char-acteristics and reviewed relevant literatures.Results All 5 ca-ses were male,and mean age was 66 years.Five patients had a history of smoking,three patients were treated with cough and blood in sputum as the first symptom,one was treated with a history of pulmonary tuberculosis combined with limb mobility disorder,and one was diagnosed with pulmonary nodules by physical examination.Under microscopic observation,tumor cells were poorly differentiated,with solid nest sheet distribu-tion,some with glandular structure,tumor cells had abundant e-osinophilic or transparent cytoplasm,vacuolar nuclear chroma-tin,nucleoli was visible,and nuclear mitosis was common.In-flammatory cell infiltration and sheet of necrosis were seen in the stroma.Immunohistochemical staining showed 5/5 diffuse ex-pression of CK(AE1/AE3)and CK7,5/5 loss expression of BRG1,1/5 diffuse expression of p40 and CK5/6,and Ki67 proliferating index ranged from 20％to 90％.FISH tests showed that 4/4 SMARCA4 genes missed.Five patients were followed up for 2-15 months,3 patients died and 2 patients survived.Conclusions SMARCA4-dNSCLC can have extensive morphologi-cal features,high degree of malignancy,and complicated treat-ment.BRG1 deficiency is helpful for diagnosis.Deepening the understanding of SMARCA4-dNSCLC can help the clinical cor-rect choice of treatment strategies and accurately evaluate patient prognosis.

Purpose::Head injury criterion (HIC) companied by a rotation-based metric was widely believed to be helpful for head injury prediction in road traffic accidents. Recently, the Euro-New Car Assessment Program utilized a newly developed metric called diffuse axonal multi-axis general evaluation (DAMAGE) to explain test device for human occupant restraint (THOR) head injury, which demonstrated excellent ability in capturing concussions and diffuse axonal injuries. However, there is still a lack of comprehensive understanding regarding the effectiveness of using DAMAGE for Hybrid III 50th percentile male dummy (H50th) head injury assessment. The objective of this study is to determine whether the DAMAGE could capture the risk of H50th brain injury during small overlap barrier tests.Methods::To achieve this objective, a total of 24 vehicle crash loading curves were collected as input data for the multi-body simulation. Two commercially available mathematical dynamic models, namely H50th and THOR, were utilized to investigate the differences in head injury response. Subsequently, a decision method known as simple additive weighting was employed to establish a comprehensive brain injury metric by incorporating the weighted HIC and either DAMAGE or brain injury criterion. Furthermore, 35 sets of vehicle crash test data were used to analyze these brain injury metrics.Results::The rotational displacement of the THOR head is significantly greater than that of the H50th head. The maximum linear and rotational head accelerations experienced by H50th and THOR models were (544.6 ± 341.7) m/s 2, (2468.2 ± 1309.4) rad/s 2 and (715.2 ± 332.8) m/s 2, (3778.7 ± 1660.6) rad/s 2, respectively. Under the same loading condition during small overlap barrier (SOB) tests, THOR exhibits a higher risk of head injury compared to the H50th model. It was observed that the overall head injury response during the small overlap left test condition is greater than that during the small overlap right test. Additionally, an equation was formulated to establish the necessary relationship between the DAMAGE values of THOR and H50th. Conclusion::If H50th rather than THOR is employed as an evaluation tool in SOB crash tests, newly designed vehicles are more likely to achieve superior performance scores. According to the current injury curve for DAMAGE and brain injury criterion, it is highly recommended that HIC along with DAMAGE was prioritized for brain injury assessment in SOB tests.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective To investigate the equivalent conversion of head injury criterion(HIC)under anterior-posterior(AP)and lateral-medial(LM)craniocerebral impact for mild craniocerebral injury in rats using motor evoked potential(MEP)and β-amyloid precursor protein(β-APP)immunohistochemistry(IHC).Methods Sixty healthy adult male SD rats were randomly divided into 0 m control group,0.5 m-AP and 0.5 m-LM injury groups,and 1 m-AP and 1 m-LM injury groups(12 rats in each group).The control group did not undergo any impact injury experiment.After the impact injury experiment,the injury and control groups were subjected to excessive anesthesia to produce β-APP immunohistochemical stained slices,and the percentage of positive area and integral optical density(IOD)in the brainstem pyramidal tract area of the slices were determined.The MEP groups were divided in the same manner as the IHC groups and the MEP amplitudes of the MEP and control groups were measured after the impact injury experiment.Results With an increase in the degree of injury,the decrease in MEP amplitude,percentage of positive areas,and IOD in the injury groups significantly increased.When the degree of injury was low,the sensitivity of IHC was higher than that of MEP.When the degree of injury was the same,the HIC in the LM direction was lower than that in the AP direction.When the HIC was the same,the degree of injury in the LM direction was greater than that in the AP direction.Conclusions The joint evaluation of MEP and β-APP can provide experimental references for the study of HIC equivalent conversion in AP-LM craniocerebral impact injury.