Quality evaluation for Beidougen Formula Granules / 中成药

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

Background@#Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. @*Methods@#In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. @*Results@#Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. @*Conclusions@#We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Benzodiazepines in complex biological matrices:Recent updates on pretreatment and detection methods / 药物分析学报

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Retrospective Analysis of Death Cases of Oral Diphenidol Hydrochloride Poisoning / 法医学杂志

OBJECTIVES@#To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths.@*METHODS@#The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected.@*RESULTS@#In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied.@*CONCLUSIONS@#Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme.@*METHODS@#The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests.@*RESULTS@#Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001).@*CONCLUSION@#For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.

Application of dynamic contrast enhanced status in multiparametric magnetic resonance imaging for prostatic cancer with PI-RADS 4 lesion / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the diagnostic value of dynamic contrast enhanced (DCE) of multiparametric magnetic resonance imaging (mpMRI) for prostate imaging reporting and data system (PI-RADS) 4 lesion in prostate peripheral zone.@*METHODS@#The clinical data of patients with PI-RADS 4 lesion in prostate peripheral zone who underwent prostate biopsy from January 2018 to September 2021 in Peking University First Hospital were retrospectively included. According to DCE status, the patients were divided into the conventional group (4 points for diffusion-weighted imaging) and the comprehensive group (3 points for diffusion-weighted imaging + 1 point for DCE positive). Pearson's chi-square test or Fisher's exact test for comparison was conducted between prostate cancer and non-cancer patients. Univariate and multivariate Logistic regression were performed to analyze the correlation of positive biopsy with age, total prostate specific antigen (PSA), free PSA/total PSA (f/tPSA), prostate volume (PV), PSA density (PSAD) and DCE status.@*RESULTS@#Among the 267 prostate biopsy patients, 217 cases were diagnosed as prostatic cancer (81.27%) and 50 cases were non-cancer (18.73%). Statistical analysis between the prostatic cancer group and the non-cancer group showed that there were significant differences in age, tPSA, PV and PSAD (all P < 0.05), but no significant differences in f/tPSA between the two groups. About different PI-RADS 4 lesion groups, the conventional group and the comprehensive group showed significant difference in biopsy results (P=0.001), and the conventional group had a higher positive rate. The PV of comprehensive group was larger than that of the conventional group. Among the prostate cancer patients diagnosed by biopsy, statistical analysis between the conventional group and comprehensive group showed that there were not significant differences in International Society of Urological Pathology (ISUP) grade and distinguishing clinically significant prostate cancer (all P > 0.05). Logistic univariate analysis showed that the diagnosis of prostate cancer was related to age, tPSA, f/tPSA, PV and DCE group status (all P < 0.05). Multivariate analysis showed that age, tPSA, PV and DCE group status (all P < 0.05) were independent risk factors for the diagnosis of prostatic cancer.@*CONCLUSION@#tPSA, f/tPSA, PV and PSAD are the indicators to improve the diagnosis of prostatic cancer with PI-RADS 4 lesion in peripheral zone lesions. DCE status is worth considering, so that we can select patients for biopsy more accurately, reduce the rate of missed diagnosis of prostate cancer as well as avoid unnecessary prostate puncture.

Design and application of mobile intelligent inventory system for medical equipment / 医疗卫生装备

Objective To design a mobile intelligent inventory system for medical equipment to solve the problems of medical equipment management in efficiency and accuracy due to manual inventory.Methods A mobile intelligent inventory system for medical equipment was designed with radio frequency identification(RFID)technology,optical character recognition technology and wireless network technology,which was composed of a photo acquisition device,an inventory workstation,a wireless router,a mobile cart,a RFID barcode printer and a mobile power source.The photo acquisition device realized equipment image collection with a photography App in the cell phone or tablet computer;the inventory workstation consisted of an offline inventory system and an equipment nameplate recognition system,which built inventory tasks with Tomcat Web service and identified equipment nameplate information through feature-based learning algorithms;the RFID barcode printer controlled label printing by an offline inventory system embedded into its driver.Results The system developed executed medical equipment inventory and labeling simultaneously,which established electronic file for each piece of equipment to realize accounts corresponding to the equipment accurately.Conclusion The inventory system developed enhances the efficiency of medical equipment inventory,standardizes the flow of medical equipment ledger management and provides support for life-cycle management of medical equipment.[Chinese Medical Equipment Journal,2023,44(11):45-49]

Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes / 中华妇产科杂志

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Lingnan Fire-needle on Inhibiting Melanocyte Apoptosis in Vitiligo Model Mice by Regulating Hippo-YAP Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

Treatment Progress in Diminished Ovarian Reserve: Western and Chinese Medicine / 中国结合医学杂志

Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment.

Comparative Study between ZOOMit and Conventional Intravoxel Incoherent Motion MRI for Assessing Parotid Gland Abnormalities in Patients with Early- or Mid-Stage Sjögren’s Syndrome

Objective@#To compare the reproducibility and performance of quantitative metrics between ZOOMit and conventional intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the diagnosis of early- and mid-stage Sjögren’s syndrome (SS). @*Materials and Methods@#Twenty-two patients (mean age ± standard deviation, 52.0 ± 10.8 years; male:female, 2:20) with early- or mid-stage SS and 20 healthy controls (46.9 ± 14.6 years; male:female, 7:13) were prospectively enrolled in our study.ZOOMit IVIM and conventional IVIM MRI were performed simultaneously in all individuals using a 3T scanner. Quantitative IVIM parameters - including tissue diffusivity (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) - inter- and intra-observer reproducibility in measuring these parameters, and their ability to distinguish patients with SS from healthy individuals were assessed and compared between ZOOMit IVIM and conventional IVIM methods, appropriately. MR gland nodular grade (MRG) was also examined. @*Results@#Inter- and intra-observer reproducibility was better with ZOOMit imaging than with conventional IVIM imaging (ZOOMit vs. conventional, intraclass correlation coefficient of 0.897–0.941 vs. 0.667–0.782 for inter-observer reproducibility and 0.891–0.968 vs. 0.814–0.853 for intra-observer reproducibility). Significant differences in ZOOMit f, ZOOMit D*, conventional D*, and MRG between patients with SS and healthy individuals (all p < 0.05) were observed. ZOOMit D* outperformed conventional D* in diagnosing early- and mid-stage SS (area under receiver operating curve, 0.867 and 0.658, respectively; p = 0.002). The combination of ZOOMit D*, MRG, and ZOOMit f as a new diagnostic index for SS, increased diagnostic area under the curve to 0.961, which was higher than that of any single parameter (all p < 0.01). @*Conclusion@#Considering its better reproducibility and performance, ZOOMit IVIM may be preferred over conventional IVIM MRI, and may subsequently improve the ability to diagnose early- and mid-stage SS.

Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium / 中国中药杂志

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron / 中国天然药物

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 μmol·L-1.

Short-term combined treatment with exenatide and metformin for overweight/obese women with polycystic ovary syndrome / 中华医学杂志(英文版)

BACKGROUND@#Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.@*METHODS@#Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.@*RESULTS@#Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.@*CONCLUSIONS@#COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.

Long-term outcomes of intravascular ultrasound-guided drug-eluting stent implantation in patients with chronic kidney disease: ULTIMATE CKD subgroup analysis / 中华心血管病杂志

Objective: To explore the long-term effect of intravascular ultrasound (IVUS) guidance on patients with chronic kidney disease (CKD) undergoing drug-eluting stent (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. From August 2014 to May 2017, 1 448 patients with coronary heart disease undergoing DES implantation were selected from 8 domestic centers and randomly divided into two groups in the ratio of 1∶1 (IVUS or coronary angiography guided stent implantation). A total of 1 443 patients with the baseline serum creatine available were enrolled. The patients were divided into CKD group and non CKD group. CKD was defined as the estimated glomerular filtration rate (eGFR) derived from Cockcroft Gault (CG) formula< 60 ml·min-1·1.73 m-2 for at least 3 months. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target vessel myocardial infarction, and clinically-driven target vessel revascularization. Kaplan Meier method was used for survival analysis, and log rank test was used to compare the occurrence of end-point events in each group. Cox proportional hazards model was used to calculate HR and 95%CI, and interaction was tested. Multivariate Cox regression was used to analyze the independent influencing factors of TVF. Results: A total of 1 443 patients with coronary heart disease were enrolled in this study, including 349 (24.2%) patients in CKD group and 1 094 patients in non CKD group. In CKD group, IVUS was used to guide stent implantation in 180 cases and angiography was used in 169 cases; in non CKD group, IVUS was used to guide stent implantation in 543 cases and angiography was used in 551 cases. Three-year clinical follow-up was available in 1 418 patients (98.3%). The incidence of TVF in CKD group was 12.0% (42/349), which was higher than that in non CKD group (7.4% (81/1 094) (P = 0.01). The difference was mainly due to the higher cardiac mortality in CKD group (4.6% (16/349) vs. 1.5% (16/1094), P<0.001). In CKD group, the incidence of TVF in patients who underwent IVUS guided stent implantation was lower than that in angiography guided stent implantation (8.3% (15/180) vs. 16.0% (27/169), P = 0.03). There was no significant difference in the incidence of TVF between IVUS guided stent implantation and angiography guided stent implantation in non CKD group (5.9% (32/543) vs. 8.9% (49/551), P = 0.06), and there was no interaction (P = 0.47). Multivariate Cox regression analysis showed that IVUS guidance (HR = 0.56, 95%CI 0.39-0.81, P = 0.002), CKD (HR = 1.83, 95%CI 1.17-2.87, P = 0.010) and stent length (every 10 mm increase) (HR = 1.11, 95%CI 1.04-1.19, P = 0.002) were independent risk factors for TVF within 3 years after DES implantation. Conclusions: CKD patients undergoing DES implantation are associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in comparison with angiography guidance in patients with CKD.

Three dimensional nephrometry system for partial nephrectomy: Our initial exploration / 北京大学学报(医学版)

OBJECTIVE@#To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value.@*METHODS@#The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed.@*RESULTS@#A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm3 and (33.0±36.4) cm3, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation.@*CONCLUSION@#Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC).@*METHODS@#Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed.@*RESULTS@#There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic.@*CONCLUSION@#Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Effects of bevacizumab on familial epistaxis caused by hereditary hemorrhagic telangiectasia / 中华耳鼻咽喉头颈外科杂志

Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People's Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients' self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t=9.708, P<0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t=6.814, P<0.01; epistaxis duration: 0.85±0.91 vs 3.00±0.73, t=8.845, P<0.01; epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t=10.696, P<0.01; treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t=9.539, P<0.01; anemia: 0.41±0.50 vs 0.89±0.32, t=4.914, P<0.01; blood transfusion: 0.11±0.32 vs 0.41±0.50, t=3.309, P<0.01; ESS standardized score: 2.50±2.45 vs 7.60±1.30, t=9.344, P<0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t=6.864, P<0.01). Among the 27 patients, there were 8 cases of HHT1 (ENG gene) and 19 cases of HHT2 (ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups (P>0.05). There was no significant difference in ESS scores between the two groups before and after treatment (P>0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.