1.Effect of Compatibility of Wujiwan on Pharmacokinetics and Tissue Distribution of Representative Components
Yu DONG ; Ying CHEN ; Zipeng GONG ; Qing YANG ; Xiaogang WENG ; Yajie WANG ; Xiaoxin ZHU ; Chenhao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):105-113
ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan, and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups, including Wujiwan group(A group, 62.96 g·L-1), Coptidis Rhizoma group(B group, 38.4 g·L-1), processed Euodiae Fructus group(C group, 5.88 g·L-1) and fried Paeoniae Radix Alba group(D group, 18.68 g·L-1), with 65 rats in each group, and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma, liver, small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components[berberine(Ber), palmatine(Pal), evodiamine(Evo), rutecarpine(Rut) and paeoniflorin(Pae)] in Wujiwan, their concentrations in plasma, liver, small intestine and brain were detected at different time, plasma samples were processed by protein precipitation, and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component, and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve(AUC0-t) of the five representative components were ranked as follows:Ber and Pal were small intestine>liver>blood, Evo and Rut were liver>small intestine>plasma, Pae was small intestine>plasma, which was not detected in the liver, no other components were detected in brain except for Ber. In comparison with plasma and other tissues, peak concentration(Cmax) of Ber, Pal, Evo, and Rut were the highest and time to peak(tmax) were the lowest in the liver of A group. In plasma, the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group, tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver, compared with B-D groups, Cmax values of 5 representative components except Pae were elevated, AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine, half-life(t1/2) of each representative components in A group was elevated and tmax was decreased, and Cmax of each representative ingredient except Pal was decreased, AUC0-t values of Ber and Pal were increased, whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine, as the effector organ, is the most distributed, followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility, which is more favorable to the exertion of its pharmacodynamic effects.
2.Effect of Tongxinluo Capsules on Use of Anti-ischemic Drugs in Patients with Chronic Coronary Syndrome of Qi Deficiency and Blood Stasis: A Multicenter, Prospective Cohort Study
Chenhao ZHANG ; Jia WANG ; Yiying LIU ; Xiaohe YANG ; Xuesen WANG ; Meili GAO ; Yu DONG ; Xiaotao LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):149-156
ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome (CCS) of Qi deficiency and blood stasis. MethodA multicenter,prospective cohort study was conducted,with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group (combination of traditional Chinese and western medicine) and a non-exposed group (western medicine alone),and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3,6,12 months. ResultA total of 186 patients were enrolled,with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up,the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group (P<0.01),and this difference remained statistically significant at 6 months (P<0.05) but was no longer significant at 12 months. At the 3- and 6-month follow-ups,there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However,at the 12-month follow-up,the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group (P<0.01). At the 3-month follow-up,both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline (P<0.05),with a more pronounced reduction in the exposed group (P<0.05). At the 6-month follow-up,the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline (P<0.05),while no significant changes were observed in the non-exposed group. At the 12-month follow-up,the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant (P<0.05),while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.
3.Minimally invasive aortic valve replacement with Perceval sutureless aortic bioprosthesis through upper ministernotomy or right anterior thoracotomy
Peng YANG ; Yi XIE ; Chenhao WANG ; Yu LIU ; Qianlei LANG ; Wenfan LI ; Jia HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(03):439-445
Objective To evaluate the clinical effect of minimally invasive aortic valve replacement with Perceval sutureless aortic bioprosthesis in upper ministernotomy or right anterior thoracotomy. Methods From March to November 2022, the patients with simple aortic valve disease were enrolled in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University. After preoperative evaluation, Perceval sutureless bioprosthesis was successfully used to perform aortic valve replacement through the upper ministernotomy or right anterior thoracotomy. The perioperative clinical data and ultrasonic measurement data of all patients were recorded. Results A total of 5 patients with simple aortic valve disease were included, including 3 females and 2 males, with a mean age of 71.2 years. Perceval sutureless bioprosthesis was successfully implanted in 5 patients, with a success rate of 100%. There were 3 patients receiving upper ministernotomy and 2 patients receiving right anterior thoracotomy. Two patients underwent ascending aortic plasty at the same time. The mean cardiopulmonary bypass time was 61.0 min, and aortic cross-clamping time was 32.2 min. All patients were discharged successfully without perivalvular leakage, atrioventricular block or stroke. Conclusion The implantation method of Perceval sutureless bioprosthesis is simple, which can effectively reduce the perioperative risk by shortening the overall operation time, cardiopulmonary bypass time and aortic cross-clamping time. At the same time, its clinical application has promoted the development and popularization of minimally invasive aortic valve replacement, which together with Perceval sutureless bioprosthesis effectively combinates surgical effect and minimally invasive treatment, and has a good clinical application prospect because of its reliable safety and effectiveness.
4.Two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection complicated with distal malperfusion syndrome
Peng YANG ; Yi XIE ; Yu LIU ; Yu ZHANG ; Qianlei LANG ; Wenfan LI ; Chenhao WANG ; Zhenghua XIAO ; Jia HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):585-593
Objective To evaluate the clinical efficacy of two-stage retrograde hybrid repair for acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome. Methods From May 2019 to December 2022, the patients presented with acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome treated in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University were enrolled. After preoperative evaluation, all patients underwent priority emergency interventional surgery to improve distal malperfusion, and then underwent two-stage hybrid surgery to repair proximal aortic lesions. The perioperative clinical and imaging data were retrospectively analyzed. Results Five patients were collected, including 4 males and 1 female, with a median age of 58 years. The main manifestations were lower limb ischemia and renal insufficiency in 3 patients, and poor intestinal perfusion in 2 patients. All patients were given priority to interventional surgery to implant graft stents or bare stents and necessary branch artery intervention, and then successfully performed two-stage hybrid surgery, including type Ⅰhybrid surgery for 2 patients, type Ⅱ hybrid surgery for 1 patient and type Ⅲ hybrid surgery for the other 2 patients, with a success rate of 100.0%. All patients were discharged successfully, and the function of the organs with poor perfusion returned to normal. Only 1 patient recovered to grade 4 muscle strength of the diseased lower limbs upon discharge. No adverse events such as amputation, exploratory laparotomy and intestinal resection or long-term hemodialysis occurred. Conclusion The application of two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome is safe and effective, and is helpful to improve the perioperative survival rate, and clinical outcomes of such patients.
5.Biological and physicochemical properties of bioactive ion modified brushite cements
Cheng ZENG ; Huanhuan YU ; Yukang GONG ; Chenhao WANG ; Yinen ZHANG ; Wenshan GAO
Chinese Journal of Tissue Engineering Research 2024;28(22):3561-3568
BACKGROUND:As a bone replacement and filling material,calcium phosphate stone bone cement has good biocompatibility,bone conductivity,and other advantages,especially its better biodegradability compared to other calcium phosphate bone cements.It has important application value in bone repair.However,due to its limitations such as insufficient mechanical properties,fast solidification reaction,and poor injection performance,it is currently only suitable for the repair of non weight-bearing bone. OBJECTIVE:To explore the modification of brushite cements with bioactive ions(metal and non metal ions)to expand its application range. METHODS:The author used PubMed,ScienceDirect,CNKI,and WanFang to search the literature published between 2018 and 2023 with the search terms"metal ion,iron,copper,strontium,magnesium,zinc,non-metal ion,modification,bone,brushite cements"in Chinese and"metal ion,iron,Fe,copper,Cu,strontium,Sr,magnesium,Mg,zinc,Zn,non-metal ion,modification,bone,brushite cements"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant and duplicate articles were excluded.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Bioactive ions affect the hydration process of calcium phosphate bone cement.Different ions are substituted by ions and incorporated into the crystal structure of calcium phosphate bone cement,changing the crystal morphology of the cement and causing changes in physical and chemical properties such as setting time,injectability,and compressive strength.(2)Ionic modified calcium phosphate bone cement produces different ion release effects due to different crystal structures.Different types of ions have properties such as promoting angiogenesis/osteogenesis,antibacterial,anti-tumor,etc.In addition,calcium phosphate bone cement has good biodegradability,which has great advantages for the performance of various ions.(3)The physicochemical properties of calcium phosphate bone cement modified with different ions are as follows:iron,copper,strontium,magnesium,zinc,silver,and cobalt can prolong the setting time.Strontium,and magnesium can improve injection performance.Copper,strontium,magnesium,silver and silicon can enhance compressive strength.The ions that can simultaneously improve the three physical and chemical properties of calcium phosphate bone cement include strontium and magnesium.Good physical and chemical properties are a prerequisite for clinical application,so improving the setting time,injectability,compressive strength,and other properties of calcium phosphate bone cement with ions is of great significance for the research and application of bone cement.(4)The biological properties of calcium phosphate bone cement modified with different ions are as follows:copper,strontium,magnesium,zinc,cobalt,lithium,selenium,and silicon have promoting angiogenesis/osteogenic effects.Iron,copper,magnesium,zinc,and silver have antibacterial properties.Magnesium ions have anti-inflammatory properties.Copper and selenium have anti-tumor properties.(5)In summary,magnesium ions can improve the setting time,injectability,and compressive strength of calcium phosphate bone cement,while also promoting neovascularization/osteogenesis,antibacterial properties,and have good application prospects for the treatment of bone defects with concurrent infections.In addition,copper also has anti-tumor properties,so copper ions have great potential in the treatment of bone defects caused by infections and tumors.However,relevant research is still in the basic research stage,and the effects of different ion doping concentrations and synthesis conditions on the physicochemical properties of calcium phosphate bone cement need to be further explored.At the same time,the impact of biological properties also needs to be studied and observed for a longer period of time.
6.MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer
Zhang HAOWEI ; Li QIXIN ; Guo XIAOLONG ; Wu HONG ; Hu CHENHAO ; Liu GAIXIA ; Yu TIANYU ; Hu XIAKE ; Qiu QUANPENG ; Guo GANG ; She JUNJUN ; Chen YINNAN
Journal of Pharmaceutical Analysis 2024;14(6):863-877
Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.
7.Application of perineal single-port robot-assisted radical prostatectomy
Li XU ; Chenhao YU ; Wenjin AN ; Shibin ZHU ; Haiyi HU ; Kangxin NI ; Gonghui LI
Chinese Journal of Urology 2024;45(8):598-602
Objective:To investigate the effect of perineal single-port robot-assisted radical prostatectomy.Methods:A retrospective analysis was conducted on clinical data from 60 patients who underwent perineal single-port robot-assisted laparoscopic radical prostatectomy at our hospital between July 2019 and July 2022. The mean age of the patients was (65.9±7.6) years and the mean BMI was (24.1±2.9) kg/m 2. The median (IQR) prostate volume was 32.7 (23.8, 41.2) ml, and the median (IQR) preoperative PSA value was 8.8 (6.8, 12.6) ng/ml. Preoperative pathology revealed a Gleason score of 6 in 21 patients, Gleason score of 7 in 35 patients and Gleason score of 8 in 4 patients. There were 12 patients clinically staged as T 1 and 48 patients as T 2. A total of 18 patients underwent a total of 23 previous abdominopelvic surgeries. The patient is placed in an exaggerated lithotomy position with the head down and feet elevated approximately 15°. A 3-5 cm incision was made approximately 2 cm above on the mid-perineum between the bilateral ischial tuberosities. Next, the rectourethral muscle was divided, and the space anterior to the rectum was developed by blunt dissection. The levator ani muscles were separated to expose Denonvilliers’ fascia. Then, the disposable multi-channel laparoscopic surgical access system is inserted with a surgical wound protector. Denonvilliers’ fascia was incised transversely and the ampulla of the vas deferens, which were subsequently divided. Blunt separation is performed on both sides along the capsule of the prostate, and then, the vascular pedicles of the prostate are ligated. The membranous urethra was severed after complete urethral separation at the tip of the prostate at the urethral junction. The bladder neck was freed and dissected. The prostate and seminal vesicles were removed and a vesicourethral anastomosis is performed. A perineal drain were left in place. Preoperative and postoperative variables, complications, early urinary continence rate(Return of urinary continence status was defined as using no more than one safety pad per day) and oncological outcomes of patients were recorded. Results:All 60 surgeries were successfully completed without conversions or additional incisions. The median (IQR) total operative time was 200.0(153.8, 236.3) min, the median (IQR) console operating time was 107.5(90.0, 150.0) min and the median (IQR) estimated blood loss was 50.0(50.0, 100.0) ml. Positive surgical margins were detected in five patients (8.3%). The continence rate was 43.1%(22/51), 64.7%(33/51), 92.0%(46/50) and 98.0%(49/50), and the PSA undetectable rate was 94.6%(48/51), 98.2%(49/51), 96.6%(47/50) and 100%(50/50) at the 1, 3, 6, and 12 months after surgery. Only 1(1.7%) patient experienced biochemical recurrence 9 months after surgery. The overall complication rate was 20%, including two cases of acute respiratory distress syndrome, one case of rectal injury, one case of urinary tract injury, two cases of poor wound healing, three cases of incision infection, two cases of urinary tract infection and one case of bladder neck-urethral orifice anastomotic stricture.Conclusions:Perineal single-port robot-assisted radical prostatectomy might be safe and feasible surgical treatments for localized prostate cancer, especially for patients with a history of complex abdominal or pelvic surgery. It also showed advantages in early continence. The anatomical structure of the perineal region should be considered, and the correct incision position should be chosen. Specific incision protection measures should also be used for the incision in this particular area of the perineal region to reduce the risk of perioperative complications.
8.Management and operation of extra-large Fangcang hospitals: experience and lessons from containing the highly contagious SARS-CoV-2 Omicron in Shanghai, China.
Yun XIAN ; Chenhao YU ; Minjie CHEN ; Lin ZHANG ; Xinyi ZHENG ; Shijian LI ; Erzhen CHEN ; Zhongwan CHEN ; Weihua CHEN ; Chaoying WANG ; Qingrong XU ; Tao HAN ; Weidong YE ; Wenyi XU ; Xu ZHUANG ; Yu ZHENG ; Min CHEN ; Jun QIN ; Yu FENG ; Shun WEI ; Yiling FAN ; Zhiruo ZHANG ; Junhua ZHENG
Frontiers of Medicine 2023;17(1):165-171
9. Research progress on the relationship between pediatric epilepsy and vitamin D
Chenhao LI ; Wenhao YAN ; Yuxia CHAI ; Zeyun LI ; Xihua YU ; Yanyan LI ; Kun LI ; Zeyun LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1299-1306
Epilepsy is a long-term, chronic, recurrent, multi-factorial, multi-symptomatic nervous system disease, and was caused by abnormal discharge of brain neurons. Etiology can cause irreversible brain dysfunction and even death. There are about 6.5 million children with epilepsy in China, with incidence rate twice that of adult, presenting serious threaten to children's growth and development. Vitamin D has been well-known for crucial importance to development of nervous, skeletal, and immune system. Studies have found that pediatric epilepsy as well as other neurological diseases were closely related with vitamin D deficiency. First, a large number of studies have shown that vitamin D in children with epilepsy is affected by epilepsy itself; second, the use of anti-seizure medicines can alter metabolism of vitamin D by inducing cytochrome oxidases; third, the inducement was concerned to varieties, combination and duration of anti-seizure medicines; fourth, it was expected that supplement of vitamin D during antiepileptic treatment would guarantee an improvement of treating given that anti-seizure medicines may lead to deficiency of vitamin D. Large numbers of researches have reported on the correlation ship between pediatric epilepsy and vitamin D. However, there is still a lack of systematic review. This article aims to retrospect the research progress of relationship between pediatric epilepsy and vitamin D, and provide valuable feedbacks on further treatment of pediatric epilepsy.
10.Epidemiological characteristics of lower extremity deep venous thrombosis in patients with femoral fracture
Chenhao DOU ; Tianhua LI ; Shuhong YANG ; Qing LU ; Qian GENG ; Yahui ZHANG ; Jingjing YU ; Junqin DING ; Yuting KOU ; Xue WANG ; Peng GU ; Mengna HU ; Fang LIU
Chinese Journal of Orthopaedic Trauma 2022;24(3):262-266
Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

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