ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0～7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100％)and Pepsinogen Ⅰ(83％),focally positive for H+/K+-ATPase(58％).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.

The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

After entering the body from the drug delivery site, antitumor nanomedicines need to cross a series of physiopathological barriers to reach the target site of action to effectively exert antitumor therapeutic effects. The ligand modification strategy is a classic method to enhance the efficiency of nanomedicine delivery in vivo, but the contradiction between the single ligand modification strategy, which is characterized by unity and stage, and the in vivo delivery process, which is characterized by versatility and whole-process characteristics, determines that nanomedicines modified by a single ligand alone cannot satisfy the target efficacy requirements. Therefore, the use of multiligand combinatorial modification strategies by virtue of nanomedicine surface area advantages is key to advancing the next generation of smart nanomedicines. In this paper, on the basis of summarizing and classifying the commonly used functional ligands for in vivo delivery, the advantages and research progress of multiligand combination modification of antitumor nanomedicines are discussed with special focus, and the multiligand combination modification is classified as synergistic and complementary according to the combination of the ligands, which is of great significance to ensure that antitumor nanomedicines can overcome the multiple physiopathological barriers to achieve precise delivery.

Objective To investigate the efficacy of the therapy of soothing liver and strengthening spleen(shortened as Shugan Jianpi therapy)in the treatment of active thyroid-associated ophthalmopathy(TAO)complicated with dry eye,and to provide a reference basis for clinical treatment.Methods A total of 108 patients with active TAO complicated with dry eye of liver depression and qi stagnation type were randomly divided into observation group and control group,54 patients in each group.Both groups were given conventional treatment for intervention of Graves'disease,and additionally the control group was given hormone shock therapy by intravenous injection of Methylprednisolone Sodium Succinate,and the observation group was treated with Chinese medicine prescription for soothing liver and strengthening spleen orally and intravenous injection of Methylprednisolone Sodium Succinate.The treatment period lasted for 12 weeks,and then the patients were followed up till to the 6th month.The changes of clinical activity score(CAS),proptosis,ocular surface disease index(OSDI),corneal fluorescein staining(FL),Schirmer I test(SIT)and tear film break-up time(BUT)in the two groups were observed before and after the treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate in the observation group was 94.44%(51/54)and that in the control group was 74.07%(40/54),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the CAS,OSDI score and proptosis of the patients in the two groups were all lower than those before treatment(P＜0.01),and the reduction in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the indicators of tear secretion function such as SIT,FL score and BUT of patients in the two groups were improved compared with those before treatment(P＜0.01),and the improvement in the observation group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).Conclusion Shugan Jianpi therapy exerts certain clinical efficacy in treating patients with active TAO complicated with dry eye of liver depression and qi stagnation type,which can effectively relieve the proptosis,prolong the tear film break-up time,promote the secretion of tears and the repair of corneal epithelium,improve the visual function,and enhance the quality of life of the patients.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P＜0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.01),and promoted the expression of p-SHP-2 protein(P＜0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P＜0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P＜0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P＜0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P＜0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among cases presenting with influenza-like illness (ILI) in Shenzhen City from 2019 to 2023.Methods:Respiratory specimens were collected from two national sentinel hospitals in Shenzhen from March 2019 to December 2023, specifically targeting cases of ILI. The real-time PCR method was used for the detection and genotyping of HRSV. Basic demographic information was collected and used for the epidemiological analysis.Results:A total of 9 278 respiratory specimens of influenza-like cases were collected and detected, with a total positive rate of 4.77% (443/9 278) for HRSV. In 2021 (8.48%, 167/1 970), the positive rate of HRSV was significantly higher than in 2019 (3.35%, 52/1 552), 2022 (1.80%, 39/2 169), and 2023 (4.49%, 133/2 960), and the difference was statistically significant ( χ 2=102.395, P<0.001). The prevalence of HRSV was mainly in summer and early autumn (September), and there was an abnormal increase in the positive rate of HRSV in winter 2022. The highest positive rate of HRSV was in children under five years old (9.84%, 330/335). The typing results showed that in 2022, the prevalence of HRSV-A was predominant (71.79%, 28/39), and in 2023, HRSV-A and HRSV-B subtypes coexisted. Conclusions:The prevalence of HRSV in Shenzhen from 2019 to 2023 has obvious seasonality, mainly in summer and early autumn. Children under five years old are the main population of HRSV infections.