Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

A prospective multicenter clinical trial study of a domestic HeartCon third-generation magnetic and hydrodynamic levitation LVAD for the treatment of 50 cases of end-stage heart failure / 中华胸心血管外科杂志

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

CT features of gastric stromal tumors in predicting Ki-67 index expression / 中华普通外科杂志

Objective:To investigate the feasibility of multi-slice spiral CT (MSCT) imaging feature of gastric stromal tumor (GST) in evaluating Ki-67 index expression .Methods:The clinical and CT imaging data of 501 patients with GST confirmed by surgery and pathology were retrospectively studied in Zhongshan Hospital affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University from Nov 2014 to Nov 2021. By immunohistochemical results, tumors were divided into Ki-67 low expression group (Ki-67≤6%, 335 lesions) and high expression group (Ki-67>6%, 168 lesions). Multivariate logistic regression analysis was conducted.Results:Between the two groups,there were statistical differences in the longest and shortest diameter of tumor, CT value on venous phase, CT attenuation value ( Z=4.80, 4.91, 3.21, 3.29, all P<0.01) and tumor location,morphology, necrosis, ulcer, feeding artery, vascular enhancement, positive fat sign around disease, gastrointestinal bleeding ( χ2=10.77, 13.49, 8.59, 22.87, 7.59, 7.23, 7.76, 8.58, all P<0.05). Tumor ulceration positive ( OR=1.88, 95%CI: 1.17-3.03) was independent risk factor of Ki-67 high expression ( P=0.009). Gastric antrum was used as the reference for tumor location, cardia ( OR=5.41, 95% CI:1.25-23.46) was independent risk factor of Ki-67 high expression ( P=0.024). Conclusion:MSCT has a definite predictive value for the expression in Ki-67 index of GST cases.

Identification of risk factors for urethrovesical anastomotic leakage following laparoscopic radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the risk factors of urethrovesical anastomotic leakage after laparoscopic radical prostatectomy.Methods:The clinical data of 292 patients who underwent laparoscopic radical prostatectomy in the Tenth People's Hospital Affiliated to Tongji University from January to December 2021 were retrospectively analyzed. According to whether there was anastomotic leakage, the patients were divided into leakage group (27 cases) and non-leakage group (265 cases). There were no significant differences in age [(71.5±6.5) years vs. (70.2±6.4) years], body mass index [(24.5±3.6) kg/m 2 vs. (24.2±3.0) kg/m 2], prostate volume[40(27.3, 63.2)ml vs. 38(28.1, 56.2)ml], Gleason score, clinical stage, and risk classification between the leakage group and the non-leakage group ( P>0.05), but the total prostate-specific antigen in the leakage group was significantly higher than that in the non-leakage group[20.0 (9.6, 79.0) ng/ml vs. 13.7 (8.5, 25.0) ng/ml, P=0.049]. Propensity score matching (PSM) was used to match the above indicators between the leakage group and the non-leakage group as 1∶1, so that the baseline of the two groups was balanced. The perioperative indicators of the matched two groups of patients were compared and analyzed. Statistically significant indicators were selected and included in univariate and multivariate logistic regression to analyze the risk factors of anastomotic leakage after radical prostatectomy. Finally, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated. The accuracy of each factor in predicting urine leakage was obtained. Results:After PSM, 24 cases were successfully matched. The leakage group had shorter membranous urethral length (MUL) [(15.5±2.2)mm vs. (17.5±1.5)mm, P<0.001], thinner membranous urethral wall thickness (UWT) [(9.5±1.9)mm vs. (10.6±1.5)mm, P=0.024], longer anastomotic time of urethrovesical neck[(21.6±4.1)min vs. (16.9±2.9)min, P<0.001] and higher failure rate of water injection test [16.7% (4/24) vs. 4.2% (1/24), P=0.045] than the non-leakage group. There was no significant difference in other indicators between the two groups. The results of multivariate logistic regression analysis showed that short MUL ( OR=0.544, 95% CI 0.335-0.884, P=0.014), narrow UWT ( OR=0.538, 95% CI 0.313-0.924, P=0.025) and long anastomotic time of urethrovesical neck ( OR=1.519, 95% CI 1.122-2.110, P=0.009) were independent risk factors for anastomotic urine leakage. ROC curve analysis showed that the AUC of MUL, UWT, and anastomotic time were 0.789 (95% CI 0.651-0.927), 0.715 (95% CI 0.562-0.868), and 0.842 (95% CI 0.731-0.953), respectively. Conclusions:Narrow and short membranous urethra and long anastomosis time in patients with laparoscopic radical prostatectomy may be independent risk factors for postoperative anastomotic leakage, which may predict the occurrence of anastomotic leakage.

Primary adenocarcinoma of posterior urethra complicated with intestinal metaplasia in male: a case report / 中华泌尿外科杂志

Male primary adenocarcinoma of urethra is rare clinically. A patient with primary adenocarcinoma of posterior urethra complicated with intestinal metaplasia was admitted and underwent urethral mass resection. The tumor recurred 3 months after surgery and no further treatment was given for personal reasons. The purpose of this report is to improve clinicians' understanding of urethral cancer, so that patients can undergo more accurate diagnosis and treatment.

The role and value of surgeon-engineer interaction during preoperative planning of patient-specific instrumentation assisted total knee arthroplasty / 中华骨科杂志

Objective:To investigate the significance and importance of the interaction between surgeons and engineers during the preoperative planning phase of total knee arthroplasty (TKA) when utilizing patient-specific instrumentation (PSI).Methods:A retrospective review was conducted on 202 knees of PSI-assisted TKA performed on 178 patients between June 2018 and August 2022. The patients' mean age was 68.4±6.2 years, ranging from 53 to 86 years. Among the participants, there were 149 females and 29 males, 93 left knees and 109 right knees. The study involved 171 patients of osteoarthritis (193 knees) and 7 patients of rheumatoid arthritis (9 knees), with 194 knees presenting varus knees and 8 knees with valgus knees. The preoperative plan documents, from the initial engineer-designed plan to the final plan approved by the surgeon, were analyzed to assess the frequency, parameters, and reasons for adjustments made during the planning process.Results:The planning of the 202 PSI-assisted TKA was subjected to at least one round of surgeon-engineer interaction. Among the 202 TKA planning, 117 knees (57.9%) underwent modifications after discussion, with most plans (100 knees, 49.5%) being confirmed after one round of modification. Two rounds of modifications were performed on 10 knees (5.0%), and three rounds on 5 knees (2.5%). A maximum of four rounds of modifications were made on two knees (0.9%). Furthermore, in the case of the remaining 85 knees (42.1%), the surgeons promptly consented to the engineers' initial planning following the discussions. Specific adjustments were made in 106 knees (52.5%) regarding femoral parameters, 57 knees (28.2%) concerning tibial parameters, and 46 knees (22.8%) requiring adjustments to both femoral and tibial parameters. Notably, the most frequently adjusted parameter was the osteotomy thickness of the posterior femoral condyles, which was modified in 94 knees (80.3%). The reasons for adjusting femoral or tibial parameters were summarized, revealing the main factors as follows: 1) Discrepancy between the mediolateral and anteroposterior diameters of the femoral condyle; 2) Twisted deformity of the proximal tibia; 3) Severe flexion contracture deformity of the knee; 4) Collapse of the medial or lateral tibial plateau; 5) Evident anterior arch deformity of the femur.Conclusion:The interaction between surgeons and engineers plays a pivotal role in the preoperative phase of PSI-assisted TKA. Effective collaboration allows surgeons to accurately analyze the unique anatomical characteristics and pathological changes of each patient in a three-dimensional perspective, facilitating the formulation of individualized surgical plans.

A deep learning prediction model for early evaluation of treatment response to neoadjuvant chemotherapy based on ultrasound images of breast cancer patients / 中华超声影像学杂志

Objective:To investigate the feasibility of deep learning radiomics model in the prediction of neoadjuvant chemotherapy (NAC) response in breast cancer based on ultrasound images at an early stage.Methods:Between January 2018 and June 2021, 218 patients with breast cancer who underwent NAC were enrolled in the retrospective study. All patients received a full cycle of NAC before surgery and underwent standard ultrasound examination before NAC and after the second cycles of NAC. Of all the patients, 166 patients came from institution 1 (the First Affiliated Hospital of Nanjing Medical University) were allocated into a primary cohort.Based on the architecture of Resnet 50 convolutional neural, a deep learning prediction model was built.Further validation was performed in an external testing cohort ( n=52) from institution 2 (General Hospital of Eastern Theater Command, PLA). The clinical model was constructed using independent clinical variables. To evaluate the predictive performance, areas under the curve (AUCs) of these models and two radiologists were compared by using the DeLong method. Results:The Resnet 50 model predicted the response of NAC with accuracy. The deep learning model, achieving an AUC of 0.923 (95% CI=0.884-0.962) in the primary cohort and an AUC of 0.896 (95% CI=0.807-0.980) in the test cohort, outperformed the clinical model and also performed better than two radiologists′ prediction (all P<0.05). Furthermore, the two radiologists achieved a better predictive efficacy (AUC 0.832 and 0.808 for radiologists 1 and 2, respectively) when assisted by the DL model (all P<0.01). Conclusions:The deep learning radiomics model is able to predict therapy response in the early-stage of NAC for breast cancer patients, which could guide clinicians and provide benefit for timely treatment strategy adjustment.

Construction of predictive model for renal allograft rejection based on clinical multimodal ultrasound features / 中华超声影像学杂志

Objective:To construct a nomogram for predicting the occurrence of renal allograft rejection based on the combination of multimodal ultrasound features and clinical data.Methods:The ultrasound findings and clinical characteristics of 102 patients with transplanted kidneys who underwent renal biopsy in the General Hospital of Eastern Theater Command from January 2021 to March 2022 were analyzed retrospectively. Patients were divided into rejection group and nephropathy group according to Banff transplant kidney pathological diagnostic criteria (2017 edition). Multivariate Logistic regression was used to screen independent predictors related to the status of rejection, and nomograms were drawn based on the independent predictors. The internal validation of the nomogram was carried out by Bootstrap method, and the ROC curve and calibration curve were utilized to evaluate the diagnostic efficacy of the nomogram.Results:Blood urea nitrogen concentration, renal aortic resistance index, absolute time to peak and cortical echo were independent predictors of rejection( OR=1.073, 1.078, 0.843, 0.205; all P<0.05). Incorporating blood urea nitrogen concentration, renal aortic resistance index, absolute peak time and cortical echo, the nomogram was constructed. The AUC of the predictive model was 0.814(95% CI=0.722-0.905) and the cutoff value was 0.67(corresponding to a total score of about 157 points). Both internal verification (AUC=0.788) and calibration curve demonstrated the clinical usefulness of the nomogram. Conclusions:The nomogram for predicting the occurrence of rejection in renal allograft patients based on multimodal ultrasound features and clinical data can guide the individualized treatment of patients with renal dysfunction.

Short-Term Changes of Graft Viscosity after Anterior Cruciate Ligament Reconstruction / 医用生物力学

Objective To study the short-term variation patterns of graft viscosity after anterior cruciate ligament reconstruction (ACLR) surgery. Methods Six male New Zealand rabbits were selected. The ACLR animal model of unilateral knee was made with Achilles tendon as the graft. The experimental rabbits were euthanized 15 days after ACLR surgery, with removal of the graft, healthy anterior cruciate ligament (ACL) and Achilles tendon. The cross-sectional area and viscosity coefficient of the graft were measured, and the creep experiments were carried out under equilibrium conditions of 0.1 MPa and 1 MPa, respectively. The viscosity coefficent was calculated. Variation patterns of graft viscosity were summarize. The grafts were compared with healthy ACL. Results The cross-sectional area of the graft increased slowly within 15 days after ACLR surgery. The viscosity of ACL and graft changed nonlinearly. The viscosity coefficient was quite different under different stresses. The viscosity coefficient of the graft decreased with the time after ACLR surgery, which was more obviously under the condition of low stress. Conclusions The results are helpful to guide the implementation of early postoperative rehabilitation plan after ACLR surgery .

Treatment outcome of laparoscopic partial nephrectomy in patients with renal tumors of moderate to high complexity / 北京大学学报(医学版)

OBJECTIVE@#To investigate the treatment outcome of laparoscopic partial nephrectomy in the patients with renal tumors of moderate to high complexity (R.E.N.A.L. score 7-10).@*METHODS@#In the study, 186 patients with a renal score of 7-10 renal tumors who underwent laparoscopic partial nephrectomy in Peking University Third Hospital from February 2016 to April 2021 were selected. Laparoscopic partial nephrectomy was performed after examination. The patients were followed-up, and their postoperative hemoglobin, creatinine, complications, and length of hospital stay recorded. The data were represented by mean±standard deviation or median (range).@*RESULTS@#There were 128 males and 58 females in this group, aged (54.6±12.8) years, with body mass index of (25.4 ± 3.4) kg/m2; The tumors were located in 95 cases on the left and 91 cases on the right, with maximum diameter of (3.1±1.2) cm. The patient's preoperative hemoglobin was (142.9±15.8) g/L, and blood creatinine was 78 μmol/L (47-149 μmol/L). According to preoperative CT images, the R.E.N.A.L. score was 7 points for 43 cases, 8 points for 67 cases, 9 points for 53 cases, and 10 points for 23 cases. All the ope-rations were successfully completed, with 12 cases converted to open surgery. The operation time was 150 minutes (69-403 minutes), the warm ischemic time was 25 minutes (3-60 minutes), and the blood loss was 30 mL (5-1 500 mL). There were 9 cases of blood transfusions, with a transfusion volume of 800 mL (200-1 200 mL). Postoperative hemoglobin was (126.2±17.0) g/L. The preoperative crea-tinine was 78 μmol/L (47-149 μmol/L), the postoperative creatinine was 83.5 μmol/L (35-236 μmol/L), the hospital stay was 6 days (3-26 days), and surgical results achieved "the trifecta" in 87 cases (46.8%). In the study, 167 cases were followed up for 12 months (1-62 months), including 1 case with recurrence and metastasis, 4 cases with metastasis, and 2 cases with other tumors (1 case died).@*CONCLUSION@#Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with R.E.N.A.L. score of 7-10. Based on the complexity of the tumor, with the increase of difficulty, the warm ischemia time and operation time tend to increase gradually, while "the trifecta" rate gradually decreases. The complications of this operation are less, and the purpose of preserving renal function to the greatest extent is achieved.

Transrectal ultrasound examination of prostate cancer guided by fusion imaging of multiparametric MRI and TRUS: avoiding unnecessary mpMRI-guided targeted biopsy / 亚洲男科学杂志(英文版)

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

Effects of individualized treatment of contralateral patent processus vaginalis during laparoscopic high ligation of processus vaginalis / 现代泌尿外科杂志

【Objective】 To explore the rational management of contralateral patent processus vaginalis (CPPV) in laparoscopic high ligation of processus vaginalis. 【Methods】 A total of 300 children with unilateral oblique inguinal hernia/hydrocele who received laparoscopic high ligation of processus vaginalis in Baoding Children’s Hospital during Jun.2018 and Jun.2022 were selected and divided into two groups by random number table method, with 150 in either group. In the control group, 53 cases of CPPV were found intraoperatively, which were treated simultaneously. In the study group, 58 cases of CPPV were detected, among which 11 met the indications of high ligation and received simultaneous surgical treatment. The incidence of recurrence was compared between the two groups. 【Results】 After 1 year of follow-up, the recurrence rate was 8.62% in the study group and 1.88% in the control group (P>0.05). The detection rate of CPPV was 23.02% in children with unilateral inguinal hernia, significantly lower than that in children with unilateral hydrocele (49.07%, P<0.001). The detection rate of CPPV was 42.71% in children with left patent processus vaginalis and 32.95% in children with right patent processus vaginalis (P=0.19). The detection rate of CPPV was 62.93% in the age group of 1-2 years, significantly higher than that in other age groups (P<0.001). 【Conclusion】 The incidence of CPPV conversion into oblique inguinal hernia or hydrocele is low. Only children who meet the indications can be treated at the same time during surgery.

The Regulation of Expression and Activity of Glucose Transporter 1 / 中国生物化学与分子生物学报

Glucose transporters (GLUTs) encoded by the solute carrier family 2 (SLC2) gene belong to the major facilitator superfamily (MFS) and are responsible for the transmembrane transport of glucose in the body. As the earliest discovered member of the GLUTs, glucose transporter 1 (GLUT1) is mainly found in the blood-brain barrier and erythrocyte membrane, and plays an important role in maintaining stable blood glucose concentration and energy supply to the brain. The transmembrane transport capacity of GLUT1 is not only related to the gene expression of SLC2 A1 on the cellular membrane, but also to the transport kinetic regulation of GLUT1. Generally, SLC2 A1 expression is regulated at the transcriptional, post-transcriptional, translational and post-translational levels, and the transport kinetics regulation includes a series of GLUT1 inhibitors, such as intramembrane glycan-binding site inhibitor, extramembrane glycan-binding site inhibitor, adenosine-binding effect inhibitors and the highly selective inhibitor BAY-876. SLC2 A1 gene deletions and mutations can cause embryonic mortality and GLUT1 deficiency syndrome. In contrast, abnormally high SLC2 A1 expression is associated with various diabetic complications (e. g. diabetic retinopathy and diabetic nephropathy), neurocognitive impairment and tumorigenesis. In this paper, the structure, function, expression and activity regulation of GLUT1 and its relationship with diseases were reviewed to provide a reference for the GLUT1-related clinical research and drug development.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

The protective effect of hesperidin on cardiac and renal tissue damage in DOCA/Salt hypertensive rats / 中国药理学通报

Aim To investigate the protective effect of hesperidin (HES) on cardiorenal damage induced by DOCA/Salt hypertension and the underlying mechanisms. Methods Eighteen male SD rats were randomly divided into normal group (Ctrl), model group (DOCA/Salt), and DOCA/Salt with hesperidin group (DOCA/Salt + HES). HES was administered for four weeks. Blood pressure, serum creatinine and blood urea nitrogen were measured. The pathological changes in heart and kidney were examined by HE, Masson and Sirius red staining. The expression of α-SMA, collagen I and TGF-β were detected by Western blot. The mRNA levels of Nlrp3, TNF-α, IL-1β, IL-6 and NOXs were measured using qRT-PCR. Results Compared with the model group, HES administration significantly attenuated the occurrence of DOCA/Salt hypertension, improved renal function indicators of hypertensive rats, reduced renal and cardiac fibrosis, deduced the expression of α-SMA, collagen I and TGF-β, inhibited the expression of Nlrp3, TNF-α, IL-1β and IL-6, and decreased the expression of NOXs in renal and cardiac tissues. Conclusions HES can delay the occurrence of hypertension and protect against hypertension-induced renal and cardiac tissue damage, which may be related to the reduction of inflammatory reaction and oxidative stress by HES.

Clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion in children / 中华儿科杂志

Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.

Network Meta-analysis of oral Chinese patent medicine in adjuvant treatment of rotavirus gastroenteritis in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of rotavirus gastroenteritis(RVGE) in children based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicine in the adjuvant treatment of RVGE in children was retrieved from the databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to October 22, 2022. The quality of the included RCT was evaluated according to the Cochrane risk-of-bias tool, and the data were analyzed by RevMan 5.4 and Stata 16 software. Sixty-three RCTs were included, with 11 oral Chinese patent medicines involved, including Xingpi Yanger Granules, Weichang'an Pills, Qiuxieling Mixture, Erxieting Granules, and Changyanning Granules/Syrup. The results of the network Meta-analysis showed that in terms of clinical total effective rate, the top 3 optimal interventions were Changyanning Granules/Syrup, Xiaoer Guangpo Zhixie Oral Liquid, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the anti-diarrheal time, the top 3 optimal interventions were Shenling Baizhu Granules, Qiuxieling Mixture, and Shuangling Zhixie Oral Liquid combined with conventional western medicine. In terms of the antiemetic time, the top 3 optimal interventions were Changyanning Granules/Syrup, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the antipyretic time, the top 3 optimal interventions were Shenling Baizhu Granules, Xiaoer Shuangjie Zhixie Granules, and Qiuxieling Mixture combined with conventional western medicine. In terms of the negative conversion rate of rotavirus, the top 3 optimal interventions were Xingpi Yanger Granules, Erxieting Granules, and Cangling Zhixie Oral Liquid combined with conventional western medicine. In terms of reducing creatine kinase isoenzyme MB(CK-MB) level, the top 3 optimal interventions were Weichang'an Pills, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of adverse reactions, no se-rious adverse reactions were reported in all studies. Oral Chinese patent medicines in the adjuvant treatment of children with RVGE have their own advantages, Specifically, Changyanning Granules/Syrup + conventional western medicine focuses on improving the clinical total effective rate and shortening the antiemetic time, Shenling Baizhu Granules + conventional western medicine on shortening the anti-diarrheal time and antipyretic time, Xingpi Yanger Granules + conventional western medicine on improving the negative conversion rate of rotavirus, and Weichang'an Pills + conventional western medicine on reducing the CK-MB level. Limited by the quantity and quality of literature included in this study, the results need to be verified by high-quality RCT with a larger sample size.

Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Chemical components of Magnoliae Officinalis Cortex of different origins and with different tree ages before and after being processed with ginger juice:a qualitative and quantitative analysis / 中国中药杂志

This study aimed to investigate the impact of ginger juice on chemical profile of Magnoliae Officinalis Cortex(MOC) when they were processed together. Ultra-high-performance liquid chromatography coupled to quadrupole-orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was used for qualitative analysis of the chemical component of MOC samples before and after being processed with ginger juice. UPLC was performed to observe the content variation of eight main components in processed MOC. A total of 174 compounds were identified or tentatively deduced from processed and unprocessed MOC samples according to MS data obtained in positive and negative ion mode. After MOC was processed with ginger juice, the peak areas of most phenolics increased, while the peak areas of most phenylethanoid glycosides decreased; as for neolignans, oxyneolignans, other lignans and alkaloids, changes in the peak area were variable, and the peak areas of terpenoid-lignans varied little. Additionally, gingerols and diarylheptanoids were only detected in the processed MOC sample. The contents of syringin, magnoloside A, and magnoloside B decreased significantly in the processed MOC sample while no significant difference was observed in the contents of magnoflorine, magnocurarine, honokiol, obovatol, and magnolol. This study comprehensively explored the content variation of chemical components in processed and unprocessed MOC samples derived from different regions and with different tree ages using UPLC and UHPLC-Q-Orbitrap HRMS, and summarized the variation characteristics of various compounds. The results provide a data foundation for further research on pharmacodynamic substances of MOC processed with ginger juice.

Protective Effect of Shentong Zhuyutang-containing Serum on Chondrocytes in Rats with Knee Osteoarthritis Based on AMPK/Sirt1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Shentong Zhuyutang-containing serum against oxidative stress and apoptosis in chondrocytes of rats with knee osteoarthritis （KOA）. MethodFifty male rats were orally administered with normal saline， low-， medium-， and high-dose Shentong Zhuyutang （1.73， 3.46， 6.92 g·kg-1）， and glucosamine sulfate （0.3 g·kg-1） for two weeks. Serum samples were collected after the treatment period. The KOA model was established， and chondrocytes were isolated and randomly divided into normal group， model group， low-， medium-， and high-dose Shentong Zhuyutang-containing serum groups， and glucosamine sulfate group. During the chondrocyte culture， adenosine monophosphate （AMP）-activated protein kinase （AMPK） inhibitor Compound C （10 μmol·L-1） was added， and the cells were divided into normal group， model group， Shentong Zhuyutang-containing serum group， and Compound C + Shentong Zhuyutang-containing serum group. Cell proliferation was detected using 5-ethynyl-2'-deoxyuridine （EdU） staining. Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Reactive oxygen species （ROS） levels were measured using DCFH-DA probe. Glutathione （GSH） and malondialdehyde （MDA） levels were determined using the colorimetric method. Real-time polymerase chain reaction （PCR） was used to measure the mRNA expression levels of matrix metalloproteinase-3 （MMP-3）， MMP-13， type Ⅱ collagen （Col Ⅱ）， and Aggrecan. Western blot was performed to measure the protein expression of phosphorylated （p）-AMPK and silent information regulator factor 1 （Sirt1）. ResultCompared with the normal group， the model group showed a significant decrease in chondrocyte proliferation rate， GSH activity， Col Ⅱ and Aggrecan mRNA expression， p-AMPK and Sirt1 protein levels （P<0.01）， and increased ROS levels， MDA content， TUNEL-positive cell rate， and MMP-3 and MMP-13 mRNA expression （P<0.01）. Compared with the model group， Shentong Zhuyutang-containing serum increased the number of EdU-positive cells， GSH activity， Col Ⅱ and Aggrecan mRNA expression， p-AMPK and Sirt1 protein levels in KOA rat chondrocytes （P<0.05， P<0.01）， and decreased the TUNEL-positive cell rate， ROS levels， MDA content， MMP-3 and MMP-13 mRNA expression （P<0.05， P<0.01）. Compared with the Shentong Zhuyutang-containing serum group， the Compound C + Shentong Zhuyutang-containing serum group showed significantly reduced p-AMPK and Sirt1 protein expression， GSH activity， Col Ⅱ and Aggrecan mRNA levels （P<0.01）， and increased TUNEL-positive cell rate， ROS levels， MDA content， MMP-3 and MMP-13 mRNA levels （P<0.01）. ConclusionShentong Zhuyutang-containing serum attenuates oxidative damage and reduces apoptosis in chondrocytes of rats with KOA， and its protective effect may be associated with the activation of the AMPK/Sirt1 signaling pathway.