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.

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 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.

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.

Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

Deep brain stimulation(DBS)has become an established technique for the treatment of neurodegenerative diseases such as Parkinson disease(PD).This technique significantly improves the clinical symptoms of PD patients by directly stimulating specific basal ganglia nuclei with implanted electrodes,but its physiological mechanism of action remains unclear.The control mechanisms of eye movement involve the cerebral cortex and basal ganglia,which are extensively overlapped with the targeted network of DBS,but there are relatively few studies on the combined analysis of DBS and eye movement.This article explores the interaction mechanism between DBS and eye movement control to deeply understand the influence of DBS on eye movement function,which is of great significance for optimizing stimulation parameters and improving therapeutic effect.In addition,these studies provide new perspectives for revealing the mechanism of action of DBS and the pathophysiology of PD.

Objective:To analyze the correlation between serum antibody titers of anti-contactin associated protein-like 2 (CASPR2) antibody and clinical features and prognosis in encephalitis.Methods:A retrospective analysis was conducted on the clinical data of 31 patients diagnosed with anti-CASPR2 antibody encephalitis at the First Affiliated Hospital of Zhengzhou University from January 2018 to April 2024. Patients were divided into low titer group (≤1∶32) and high titer group (>1∶32) based on serum anti-CASPR2 antibody titers, and their clinical characteristics, auxiliary examination results, and prognosis were compared between the two groups.Results:Among the 31 patients with anti CASPR2 antibody encephalitis (male∶female=1∶1.4), there were 16 cases in the low titer group and 15 cases in the high titer group; The age of patients in the high titer group was (33.9±17.9)years, which was lower than that of patients in the low titer group [(52.9±17.9)years], and the difference was statistically significant ( P=0.006). The proportion of patients with prodromal infection in the high titer group (6/15) was higher than that in the low titer group (1/16, P=0.037). There was no statistically significant difference in the cerebrospinal fluid related test results, imaging examination of intracranial abnormal lesions, abnormal electroencephalogram, serum abnormal tumor markers, and serum abnormal rheumatic immune indicators between the two groups of patients (all P>0.05). During hospitalization, one patient in the high titer group died; During the follow-up period, one patient died and three patients relapsed, all of whom were in the high titer group. During follow-up, the mRS scores of 6 patients ranged from 3 to 5 points (indicating functional impairment), with 4 cases in the high titer group and 2 cases in the low titer group. The proportion of patients with poor prognosis in the high titer group (9/15) was higher than that in the low titer group (2/16), and the difference was statistically significant ( P=0.021). Conclusions:Patients with high serum anti-CASPR2 antibody titers and encephalitis have a lower age of onset and are prone to pre infection triggers. High antibody titers may be associated with a higher risk of disease recurrence and poor prognosis for patients.

To address the key challenges in multivariate statistical modeling,a higher-order derivative approach combined with vector space angle multiplicative error correction was proposed for establishing an acid value prediction ordinary least squares(OLS)regression model based on attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy.By using acid values measured by potentiometric titration as reference,ATR-FTIR spectroscopy was utilized for direct calibration and prediction of acid values on 96 kinds of lubricating oil samples from a wind turbine.Firstly,the simulated hyperbolic(SH)method was employed to obtain accurate fourth derivative spectrum,resolving overlapping bands and enhancing spectral selectivity.Then,from the calibration set(48 samples),informative spectral regions were identified based on correlation coefficients.Next,the sample with the highest acid value was selected as the reference and1/(1+tan(θ/2))was used as the metric relation of the spectrum to suppress the multiplicity error caused by factors such as the change of effective optical path in ATR-FTIR spectroscopy.After pretreatment of the spectrum by the method of fourth-order derivative combined with angular quantity,the number of variables decreased from 1737 to 8,and the matrix condition number decreased from 1.85×1015 to 56.34,which effectively eliminated the collinearity issue for OLS regression.Direct OLS modeling on spectral preprocessed data achieved a determination coefficient of 0.981 for 47 validation samples,with a relative error range of-8.38%-8.22%,outperforming the commonly used partial least squares(PLS)method(Determination coefficient of 0.865,relative error of-27.82%-22.38%).It was proved that effective data preprocessing significantly improved the prediction accuracy of the model.Furthermore,when the number of calibration set was compressed to 25 and the number of validation set was expanded to 70,the model retained 8 variables with a condition number of 42.60,the determination coefficient of validation set was 0.972,and the relative error ranged from-10.80%to 12.31%.Comparing with the PLS method(Determination coefficient of 0.724,relative error of-34.26%-53.84%),the improvement was more obvious,which showed that the method could still have high prediction accuracy even with fewer modeling samples as well as robustness against multiplicative error interference.

Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68％(47/53),and that of the control group was 75.47％(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P＞0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P＜0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87％(10/53),and that in the control group was 20.75％(11/53).There was no significant difference between the two groups(P＞0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.