OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg^-1） groups and metformin group （0.26 g·kg^-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.

AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

ObjectiveTo investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. MethodsA retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. ResultsAmong the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ²=6.727， P=0.009）， surgical approach （χ²=7.508， P=0.006）， margin condition （χ²=7.934， P=0.005）， and adjuvant therapy （χ²=4.608， P=0.032） were associated with the prognosis of patients. ConclusionThe clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective To explore the clinical application of ultrasound-guided transabdominal villus and amniocentesis in the prenatal diagnosis of thalassemia,and to find a suitable method for the prenatal diagnosis of thalassemia in Qinzhou.Methods A total of 531 high-risk pregnant women with severe or intermediate thalassemia during single pregnancy who were treated in the Department of Medical Genetics and Prenatal Diagnosis,Qinzhou Maternal and Child Health Hospital from March 2021 to April 2022 were selected for the study.According to different sampling methods,they were divided into control group(amniocentesis,n=415)and study group(transabdominal villus puncture,n=116).The success rate,complication rate of the two groups were compared.Results The success rate of puncture in the control group was 100％,2 cases were aborted within 2 weeks after surgery,17 cases were diagnosed with severe alpha-thalassemia,10 cases with severe β-thalassemia and 64 cases with intermediate thalassemia,48 cases with moderate and severe thalassemia induced labor.The success rate of puncture in the research group was 100％,10 cases were diagnosed with severe alpha-thalassemia,4 cases with severe β-thalassemia and 17 cases with intermediate thalassemia,and 26 cases with moderate severe thalassemia were induced labor.There was no significant difference in puncture success rate and abortion rate between the two methods(P>0.05).Conclusion Both methods are safe and effective.Transabdominal villus sampling can detect fetal thalassemia in early pregnancy,and it is worth promoting and applying in clinical practice.

Objective:To explore the clinical characteristics of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods:The clinical data of 24 patients with anti-CASPR2 encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. According to the age of first onset, the patients were divided into early onset group (10 cases, onset age<45 years) and late onset group (14 cases, onset age≥45 years). The clinical data including clinical manifestations, auxiliary examinations, and treatment response between these 2 groups were compared.Results:Among the 24 patients, there were 13 cases with epilepsy, 13 cases with cognitive decline, 13 cases with mental disorders, 14 cases with autonomic dysfunction, 8 cases with peripheral nerve hyperexcitability, 5 cases with Morvan syndrome, 5 cases with unstable walking, and 8 cases with sleep disorders. Among the 10 cases of the early onset group, 7 cases are females, and 8 cases showed epilepsy. The incidence rate of epilepsy in the early onset group was higher than that in the late onset group (5/14, Fisher exact probability, P=0.047). Among the 14 cases of the late onset group, 6 cases are females, 9 cases showed cognitive impairment and 8 cases presented with mental disorders. There were 6 cases with abnormal brain magnetic resonance imaging (MRI). The cerebrospinal fluid protein of the late onset group [0.37 (0.29, 0.58) g/L] was higher than that in the early onset group [0.22 (0.16, 0.30) g/L; Z=-2.667, P=0.008]. The modified Rankin Scale (mRS) scores before and after treatment were 3.29±0.83 and 1.50 (0.75, 2.25), which were higher than those in the early onset group [mRS scores before and after treatment were 2.10±0.99 and 0 (0, 1.00), t=-3.188, P=0.004; Z=-2.335, P=0.020]. Conclusions:There are various symptoms in patients with anti-CASPR2 encephalitis. The early onset patients are common in women, with a higher incidence of epilepsy. The late onset patients are common in males, with prominent manifestations of cognitive impairment and mental disorders, which have a greater impact on daily living abilities. And abnormal MRI findings are common, and the cerebrospinal fluid protein is higher in late onset patients. Anti-CASPR2 antibody may cause more severe immune damage to the nervous system in elderly patients.

Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To observe the clinical efficacy and safety of olanzapine tablets combined with magnesium valproate sustained-release tablets in the treatment of adolescent depressed patients.Methods Adolescents with depression were divided into control group and treatment group by simple random method.The control group was treated with oral olanzapine tablets with 5 mg·d-1 as the starting dose.After 1 week of treatment,the drug dose was adjusted according to the symptoms and kept within 20 mg·d-1.The treatment group was given oral magnesium valproate sustained-release tablet combined treatment on the basis of the control group,with 0.5 g as the initial dose,and the maximum dose was adjusted according to clinical symptoms after 1 week of treatment,and the maximum dose was no more than 1 g·d-1.Both groups were treated for 12 weeks.The clinical efficacy,excitatory amino acid(EAA),connectin level,intestinal fatty acid binding protein(Ⅰ-FABP),Hamilton depression scale(HAMD),Bech-Rafaelsen Mania Rating Scale(BRMS)and safety of the two groups were compared.Results Sixty-three cases were included in the treatment group and control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 92.06％(58 cases/63 cases)and 79.37％(50 cases/63 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the levels of EAA in the treatment group and the control group were(29.98±3.44)and(27.97±3.88)μg·mL-1;the levels of zonulin were(189.45±19.56)and(182.33±19.89)ng·mL-1;the levels of Ⅰ-FABP were(99.27±9.13)and(103.84±9.36)pg·mL-1,respectively;the HAMD scores of the treatment group and the control group were 9.88±1.03 and 10.74±1.95;the BRMS scores were 5.08±0.32 and 5.32±0.51,respectively.Compared with the control group,the differences of above indexes in the treatment group were statistically significant(all P＜0.05).The main adverse drug reactions in the two groups were weight gain,dry mouth,and drowsiness.The total incidences of adverse drug reactions in the treatment group and the control group were 12.70％and 15.87％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion Olanzapine tablets combined with magnesium valproate sustained-release tablets can effectively increase plasma Ⅰ-FABP,EAA,and zonulin levels in adolescent depressed patients,and improve HAMD and BRMS scores,with good safety.