Comparison of the fingerprint and multi-component contents between Liuwei dihuang powder decoction pieces and traditional decoction pieces with different decocting time / 中国药房

OBJECTIVE To compare the change law of multi-components in the extraction process between Liuwei dihuang powder decoction pieces and traditional decoction pieces （hereinafter referred to as powder decoction pieces and traditional decoction pieces）， and to provide scientific basis for the modern technology research of Liuwei dihuang formula. METHODS Taking powder decoction pieces and traditional decoction pieces as samples， the samples were taken when soaking for 60 min， at 0， 5， 10， 15， 20， 25， 30， 40， 50， 60 min of the first decocting and at 5， 10， 20， 30， 40 min of the second decocting， respectively. HPLC method was used to establish the fingerprints of 2 kinds of decoction pieces with different decocting time. The similarity evaluation and peak identification were performed. The contents of 8 components including 5-hydroxyfurfural， catechin， monoglycoside， loganin， swertin glycoside， dihydroquercetin， paeonol and benzoyl paeoniflorin were all determined. RESULTS With different decocting time， the similarties between 2 kinds of decoction pieces and their respective control fingerprints R were all greater than 0.98. In the fingerprints of traditional decoction pieces， five chromatographic peaks were identified， namely， 5- hydroxyfurfural， monetin， swertiaoside， dihydroquercetin and paeonol； in the fingerprints of powder decoction pieces， six chromatographic peaks were identified， namely， 5-hydroxyfurfural， monoglycoside， swertiamarin， dihydroquercetin， paeonol and benzoyl paeoniflorin. The results of content determination showed that in the first 5 minutes of the first decocting， the decocting rate of almost all the ingredients in the powder decoction pieces was faster than that of the traditional decoction pieces； after 40 min， the contents of other active ingredients were lower than those of traditional decoction pieces except for 5-hydroxyfurfural and paeonol. In the process of second decocting， except for paeonol and loganin， the contents of other ingredients in powder decoction pieces were higher than that in traditional decoction pieces； catechin was completely decocted from the traditional decoction pieces in the first decocting， while it could still be detected in the powder decoction pieces in the second decocting. There was little difference in the total decocted amount of the 8 ingredients in the two decoction pieces. CONCLUSIONS The chemical composition of powder decoction pieces of Liuwei dihuang formula has no obvious advantages compared with traditional decoction pieces， and can not save the decocting time and the amount of medicinal materials.

Method establishment and clinical practice for concentration determination of caffeine and its metabolites in urine / 中国药房

OBJECTIVE To establish a method for concentration determination of caffeine and its three metabolites， theophylline， paraxanthine and theobromine in urine， and apply it in clinical practice. METHODS Using caffeine-13C3-d3 as internal standard （IS）， and the urine samples were protein precipitated with acetonitrile； HPLC-MS/MS method was adopted to determine the concentrations of caffeine and its three metabolites. The determination was performed on Waters ACQUITY UPLC® BEH HILIC column with mobile phase consisting of 60 mmol/L ammonium acetate （A）-acetonitrile （B） （gradient elution） at the flow rate of 0.5 mL/min. The column temperature was set at 38 ℃ ， and the sample size was 2 μL. The electrospray ionization detection was operated in a positive mode by multiple reaction monitoring. The detection ions for quantitative analysis were m/z 195.1→110.0 for caffeine， m/z 181.1→124.0 for theophylline， m/z 181.1→124.0 for paraxanthine， m/z 181.1→138.0 for theobromine， and m/z 198.1→ 140.1 for IS. The above method was used to determine the concentrations of caffeine and its three metabolites in the urine of 19 infants with apnea of prematurity （AOP）. RESULTS The linear ranges of mass concentration of caffeine， theophylline， paraxanthin and theobromine were 0.200-200， 0.050-50.0，0.050 0-50.0， and 0.100-100 μg/mL， respectively. The lower limits of quantification were 0.200， 0.050， 0.050 and 0.100 μg/mL （r＞0.990）， respectively. RSDs of intra-day and intra- day precision were not above 10.37%， and matrix factors were 85.68%-109.90%； extraction recoveries were 93.53%-109.40% （RSD≤15%）， and RSDs of stability tests were all lower than 15%. The concentrations of caffeine and its three metabolites in the urine of 19 cases were （27.346±7.951）， （0.351±0.223）， （0.428±0.395） and （0.472±0.374） μg/mL， respectively. CONCLUSIONS The established HPLC-MS/MS method is simple， sensitive and can be used for the determination of caffeine and its three metabolites in urine samples of AOP.

Comparison of characteristic chromatogram and the contents of multiple indicator components of Morus alba decoction powder and decoction at different decoction time / 中国药房

OBJECTIVE To compare characteristic chromatogram and the contents of multiple indicator components of Morus alba decoction powder and decoction at different decoction time， and to provide experimental basis for the development of M. alba decoction. METHODS Taking decoction powder and decoction at different decoction time as subject， HPLC characteristic chromatogram of 2 kinds of samples were established with Similarity Evaluation Software System of TCM Chromatographic Fingerprint （2012 version）， and similarity evaluation was performed. The contents of mulberroside A， geniposide， berberine， baicalin， quercetin and luteolin in decoction powder and decoction were determined by HPLC. The contents of each indicator component and the change of total content were as the evaluation indexes to compare the difference between the two substances during decoction. RESULTS The similarities of characteristic chromatogram of the two substances ranged from 0.943 to 1.000 and 0.975 to 0.998 at different decoction time， respectively. Six indicator components of the decoction powder dissolved faster and had higher contents. The contents of each indicator component in the decoction powder when decocting at 20 minutes was 1.1-1.5 times of the decoction when decocting at 50 min， and the total content in the decoction powder was 1.2 times of the decoction. CONCLUSIONS Compared with decoction， M. alba decoction powder has the advantages of shortening the decoction time and saving traditional Chinese medicine resources. The results of this study lay a research foundation for “Zungu” to develop its preparation.

A case of mental retardation caused by a frameshift variant of SYNGAP1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with mental retardation.@*METHODS@#Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing.@*RESULTS@#The child was found to harbor a c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent.@*CONCLUSION@#The c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants and provided a basis for the diagnosis and treatment for this child.

Clinical study on core decompression in treating osteonecrosis of the femoral head of the necrotic bone-in different site / 中国骨伤

OBJECTIVE@#To analyze the clinical effect of decompression and bone grafting on osteonecrosis of the femoral head(ONFH) at different sites of necrotic lesions.@*METHODS@#A total of 105 patients with ARCOⅡstage ONFH admitted from January 2017 to December 2018 were retrospectively analyzed. There were 71 males and 34 females, with an average age of (55.20±10.98) years old. The mean course of all patients was(15.91±9.85) months. According to Japanese Inveatigation Committee (JIC) classification, all patients were divided into 4 types:17 cases of type A, 26 cases of type B, 33 cases of type C1 and 29 cases of type C2. All four groups were treated with decompression of the pulp core and bone grafting. Visual analogue scale(VAS) and Harris hip joint score were used before and at 3, 6, 12, and 24 months after the operation, and the collapse of the femoral head was observed by X-ray examination within 2 years.@*RESULTS@#All 105 patients were successful on operation without complications, and the mean follow-up duration was (24.45±2.75) months. Harris score showed that there was no statistical difference among four groups before surgery and 3, 6 months after surgery (P>0.05);at 12 and 24 months after surgery, there were significant differences among all groups (P<0.01). There were significant differences in intragroup Harris scores at preoperative and postoperative time points among four groups (P<0.01). VAS showed that there was no statistical difference among four groups before and 3, 6 months after surgery (P>0.05);at 12 and 24 months after surgery, there were significant differences among all groups (P<0.01). There were significant differences in VAS at preoperative and postoperative time points among four groups (P<0.01). None of the patients in four groups had femoral head collapse before and 3, 6 months after surgery. At 12 months after operation, there were 3 cases of femoral head collapse in group C and 4 cases in group C2(P>0.05);At 24 months after operation, 1 case of femoral head collapse occurred in group B, 6 cases in group C1 and 8 cases in group C2(P<0.05).@*CONCLUSION@#Core decompression and bone grafting can improve the effect of ONFH and hip preservation. The effect of hip preservation for ONFH is closely related to the location of the osteonecrosis lesion, so the influence of the location of lesion on the effect of hip preservation should be considered in clinical treatment, so as to make better preoperative hip preservation plan.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).@*METHODS@#This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.@*RESULTS@#The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.@*CONCLUSIONS@#TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Cloning and expression analysis of U6 promoters in Panax quinquefolius / 中国中药杂志

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head / 中华外科杂志

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

Redo laparoscopic operations for choledochojejunostomy stenosis after minimally invasive pancreaticoduodenectomy: a report of 7 patients / 中华肝胆外科杂志

Objective:To study the feasibility and safety of redo laparoscopic operations for choledochojejunostomy stenosis after minimally invasive pancreaticoduodenectomy.Methods:The clinical data of 7 patients with choledochojejunostomy stenosis which developed after minimally invasive pancreaticoduodenectomy who were treated with redo laparoscopic surgery from August 2019 to July 2021 at the Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital were retrospectively studied. There were 3 males and 4 females, with the age of (41.7±4.3) (ranged 27 to 54) years. The timing of reoperation, intraoperative blood loss, and postoperative complications were analyzed. An anastomotic restenosis was looked for on followed-up by outpatient interviews or phone calls.Results:The time interval of between diagnosis of the first postoperative anastomotic stenosis and surgery was 3-20 months, with a median of 9 months. Of the 7 patients, 5 patients underwent laparoscopic biliary anastomotic resection and reconstruction, and the remaining 2 patients underwent laparoscopic exploration of the anastomosis, removal of intrahepatic bile duct stones, and re-anastomosis. The median operative time was 180 (150-350) minutes. The median postoperative hospital stay was 6 (ranged 5 to 21) days. The intraoperative blood loss was 50 (ranged 20 to 300) ml. There was no intraoperative blood transfusion. One patient developed grade B biliary leakage after the surgery, improved with puncture and drainage. The remaining patients had no serious complications. There was no mortality. The median follow-up was 8 (ranged 1 to 23) months, during which no recurrence of biliary anastomotic stenosis occurred in all these patients.Conclusion:For patients with biliary anastomotic stenosis after minimally invasive pancreaticoduodenectomy, redo laparoscopic operations offered an alternative treatment option with satisfactory outcomes.

Case-control study on robot-assisted core decompression and conventional core decompression for early necrosis of femoral head / 中国骨伤

OBJECTIVE@#To compare clinical effect of robot-assisted core decompression and conventional core decompression in treating ARCO Ⅰ stage necrosis of femoral head.@*METHODS@#A retrospective analysis was performed on 60(unilateral operation) patients who underwent core decompression for femoral head necrosis from February 2018 to February 2020. Among them, 30 patients(30 hips) were underwent robot-assisted core decompression (RCD group), including 19 males and 11 females, aged from 17 to 58 years old with an average of(38.50±10.61) years old;30 patients(30 hips) were underwent traditional core decompression surgery (CCD group), including 20 males and 10 females, aged from 20 to 55 years old with an average of (40.63±10.63) years old. Intraoperative fluoroscopy times, intraoperative blood loss and operation time between two groups, and Harris score, visual analogue scale (VAS) before opertaion and 24 months after operation were compared.@*RESULTS@#All patients were followed up, RCD group followed up from 21 to 26 months with an average of(23.40±1.65) months, CCD group followed up from 21 to 26 months with an average of (23.30±1.66) months, and had no difference between two groups(P>0.05). The number of intraoperative X-ray fluoroscopy, intraoperative blood loss and operative time in RCD group were (9.43±1.14) times, (153.80±22.04) ml, (33.40±1.87) min, respectively;while(19.67±1.32) times, (165.04±20.41) ml and (54.75±3.46) min in CCD group respectively;and there were statistical difference between two groups(P<0.05). In addition, there were no statistical difference between two groups in Harris score and VAS at 24 months after operation(P>0.05).@*CONCLUSION@#Compared with conventional core decompression, robot-assisted core decompression could reduce the number of intraoperative fluoroscopy, shorten operation time, and reduce risk of surgery.

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.

Finite element analysis on stress concentration improvement in patellofemoral joint by releasing lateral patellar retinaculum with stiletto needle based on the theory of Jinshugu() / 中国骨伤

OBJECTIVE@#To study mechanism of improvement of stress concentration on patellofemoral joint by stiletto needle releasing lateral patellar retinaculum guided by the theory of Jinshugu() and based on the finite element model of knee joint. and to elucidate the biomechanical mechanism of stiletto needle releasing changing patellar trajectory and reducing patellofemoral joint pressure.@*METHODS@#CT data of knee joint from a normal male (aged 29, heighted 171 cm, weighted 58 kg) was selected. Starting with construction of three-dimensional model of knee joint by using finite element software, the finite element model of knee joint with complete tendonand bone structures were established through several steps, such as geometric reconstruction, reverse engineering, meshing, material assignment and loading analysis. The loading condition was set as 500 N load on knee joint, and the average tensile stress of quadriceps femoris tendon was about 200 N. To simulate the release of lateral patellar retinaculum by stiletto needle at 30 and 90 position of knee flexion in finite element model separately, and to compare the improvement of stress concentration of patellofemoral joint by stiletto needle intervention under different knee flexion conditions.@*RESULTS@#The peak stress of patellofemoral joint and tibiofemoral joint decreased after stiletto needle releasing of patellofemoral lateral retinaculum compared with before intervention, which was(1) knee flexion at 30 degrees:patellar cartilage decreased by 0.498 MPa (decreased 9.06%), femoral trochlea decreased by 0.886 MPa(decreased 16.27%);(2) knee flexion at 90 degrees:patellar cartilage decreased by 0.558 MPa (decreased 8.6%), femoral trochlea decreasedby 0.607 MPa (decreased 9.94%).@*CONCLUSION@#Releasing lateral patellofemoral retinaculum with stiletto needle could effectively alleviate the stress concentration of patellofemoral joint and reduce local stress peak value, which it is helpful to improve patellar trajectory and make stress distribution more uniform.

Two cases report of uretero-arterial fistula with long term indwelling of ureteral stent / 中华泌尿外科杂志

Ureteral artery fistula (UAF) is a rare complication after long-term indwelling of ureteral stent. In this study, two cases were presented. Both of them underwent pelvic tumor surgery and radiotherapy, and had a history of cutaneous terminal ureterostomy and long-term indwelling of ureteral stents. The first case, a 52-year-old female, was admitted to hospital because of intermittent bleeding from ureteral dermostomy for 1 week on April 2, 2020. CT examination revealed hematocele in the left upper urinary tract, and left nephrectomy was performed.However, bleeding still presented and the distal ureteral resection was performed at the same time, and partial ureteral was ligated. Postoperative diagnostic was ureteral artery fistula. After 8 months of follow-up, no recurrent bleeding presented. Another case, a 82-year-old male, was admitted to hospital because of bleeding at the ureteral dermostomy for an hour on June 15, 2020. Contrast enhanced CT examination revealed intersecting of the left ureter and common iliac artery, and interventional surgery was performed, by which UAF was diagnosed. Embolization of left internal iliac artery and stent implantation of common iliac artery and external iliac artery were performed intraoperatively. The bleeding stopped immediately after the operation, and there was no further bleeding during follow-up of 6 months.

Analysis on the Reasons and Countermeasures of Drug Network Withdrawa l under the Background of the Nor- malization of Centralized Volume-based Procurement / 中国药房

OBJECTIVE：To provid e reference for the optimization and improvement of centralized volume-based procurement policy of drugs in China. METHODS ：Six provinces ，i.e. Hebei ，Jiangsu，Hainan，Henan，Jiangxi and Yunnan ，were randomly selected nationwide by random sampling to summarize and analyze the information of drug network withdrawal from Jan. 1st，2018 to Nov. 30th，2020. RESULTS & CONCLUSIONS ：Jiangsu province had the largest number of withdrawn products from the network，being 6 331；Yunnan province had the smallest ，being 101. Product price was the leading factor for drug network withdrawal，accounting for 89.12％；the second factor was product quality ，accounting for 7.06％；the third factor was the product supply，accounting for 2.91％. At present ，there were many problems in drug network withdrawal in China ，such as inconsistent withdrawal regulations in different regions ，unclear subjects of withdrawal behavior ，difficulty in sharing information of purchasing platforms in different regions ，unreasonable bidding rules of online drugs ，etc. Some suggestions are put forward to promote standardization of drug network withdrawal ，promote information sharing among provincial platforms ，actively develop drug price monitoring，support enterprises to make reasonable pricing based on cost ，strengthen departmental linkage and guarantee of drug supply so as to improve centralized volume-based procurement policy of drugs.

Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China / 中国血吸虫病防治杂志

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

Effect of leg-length discrepancy after total hip arthroplasty on collapse of the contralateral hip in bilateral steroid-induced avascular necrosis of the femoral head / 中国医师杂志

Objective:To study the collapse of the contralateral femoral head after the total hip arthroplasty (THA) in patients with bilateral steroid-induced femoral head necrosis leg-length discrepancy (LLD) influences.Methods:A total of 108 patients with bilateral steroid-induced femoral head necrosis who were treated in Honghui Hospital Affiliated to Xi′an Jiaotong University from June 2014 to June 2016 underwent THA surgery on the hip joints that had symptoms and developed to Association Research Circulation Osseous (ARCO) Ⅲ. At the same time, the non-surgical hip-preserving treatment of the non-collapsed femoral head developed to the ARCO Ⅱ stage was performed. The follow-up period was 2 years, and 98 cases were finally included. According to the size of the leg-length discrepancy [LLD<3 mm group ( n=50), LLD≥3 mm group ( n=48)] and the type of leg-length discrepancy[non collapse side longer group ( n=58) and shorter group ( n=58)], the collapse of the femoral head and the THA were observed. Results:Finally, a total of 56 cases of femoral head collapse occurred in the non collapse side of the hip, of which 50 cases underwent THA within 24 months. There were significant statistical differences in THA and femoral head collapse between LLD<3 mm group and LLD≥3 mm group, non collapse side longer group and non collapse side shorter group ( P<0.05). The 2-year survival rate without collapse in the LLD<3 mm group and LLD≥3 mm group were 52.1% and 34.0%, respectively, and the 2-year survival rates in the longer and shorter non-collapsed limb groups were 56.9% and 22.5%, respectively. Compared with patients with moderate lesions, the survival rate of femoral heads in patients with larger lesions was lower ( OR: 4.25, 95% CI: 1.55-11.26; P=0.003). LLD<3 mm group ( OR: 0.24, 95% CI: 0.06-0.50; P<0.01) or non collapse side longer group ( OR: 0.13, 95% CI: 0.04-0.29; P<0.01) had lower risk of contralateral femoral head collapse after THA. Conclusions:For patients with bilateral steroid-induced femoral head necrosis who have collapsed lateral THA, postoperative leg-length discrepancy extremities is a potential risk factor for collapse of non-collapsed femoral head. LLD<3 mm and avoiding shortening of the uncollapsed limb may reduce the risk of collapse of the uncollapsed femoral head.

Effect of ultrasound-guided transverse abdominal plane block combined with dexmedetomidine on cesarean section / 中国基层医药

Objective:To investigate the effect of ultrasound-guided transverse abdominal plane block combined with dexmedetomidine on cesarean section.Methods:Eighty pregnant women undergoing elective cesarean section under general anesthesia in Binzhou Central Hospital from October 2017 to October 2019 were included in this study. They were randomly assigned to undergo either cesarean section under general anesthesia followed by patient- controlled intravenous analgesia (control group, n = 40) or ultrasound-guided transverse abdominal plane block combined with intravenous dexmedetomidine administration (observation group, n = 40). Analgesic efficacy and the analgesic effect on puerperas and their newborns were compared between the observation and control groups. Results:At 2, 4 and 12 hours after surgery, the Visual Analogue Scale score in the observation group was (2.1 ± 0.9) points, (2.2 ± 0.7) points, (3.0 ± 0.6) points, respectively, which was significantly lower than (4.4 ± 1.3) points, (4.9 ± 1.2) points, (3.9 ± 0.8) points in the control group, respectively ( t = 8.946, 7.854, 6.246, all P < 0.05). At 2, 4 and 12 hours after surgery, the comfort score in the observation group was (3.4 ± 0.8) points, (3.2 ± 0.7) points, (3.3 ± 0.7) points, respectively, which was significantly higher than (2.1 ± 0.7) points, (2.2 ± 0.9) points and (2.5 ± 0.8) points respectively in the control group ( t = 7.235, 6.130, 5.953, all P < 0.05). After surgery, the number of times the demand button of the anesthesia pump in the observation group was pressed was (8.4 ± 2.9), with the rate of patient satisfaction of 97.50% (39/40), which was significantly higher than that in the control group [13.1 ± 3.7, 77.50% (31/40), t = 7.036, χ2 = 9.347, both P < 0.05). At 1 and 2 days after surgery, the cumulative amount of anesthetics used for patient-controlled intravenous analgesia was (52.1 ± 1.9) mL and (121.7 ± 4.1) mL respectively, which were less than (63.6 ± 2.4) mL and (146.5 ± 5.3) mL in the control group, respectively ( t = 6.240 and 8.842, both P < 0.05). The score of extubation quality in the observation group was significantly lower than that in the control group [(1.3 ± 0.3) points vs. (3.2 ± 0.5) points, t = 6.664, P < 0.05]. There was statistically significant difference in cortisol content between the two groups at 10 minutes after extubation and at the time points of fetus removal, skin incision and intubation (all P < 0.05). In the observation group, the partial pressure of carbon dioxide in the umbilical cord blood was significantly reduced, the partial pressure of oxygen and the oxygenation index in the umbilical cord blood were significantly increased, and Apgar score at 1 minute after birth was significantly increased (all P < 0.05). Conclusion:Ultrasound-guided transverse abdominal plane block combined with dexmedetomidine can enhance the anesthetic effect on cesarean section, prolong analgesic time, reduce the amount of analgesics, improve the operation effect, reduce maternal stress responses, and improve maternal and infant health.

Platelet-rich plasma combined with core decompression and bone grafting in the treatment of non traumatic necrosis of femoral head in ARCO stageⅡ / 中国骨伤

OBJECTIVE@#To observe the clinical effect of platelet rich plasma (PRP) combined with β tricalcium phosphate bioceramic bone in the treatment of non traumatic necrosis of the femoral head in ARCO stageⅡ.@*METHODS@#From January 2017 to December 2018, 100 patients (160 hips) with ARCO stageⅡnon traumatic necrosis of the femoral head were divided into PRP group and control group. In PRP group, 50 patients (80 hips), 22 males and 28 females, aged from 18 to 65 (43.47± 7.23) years, with a course of 4 to 18 (15.8±2.9) months, underwent core decompression and bone grafting combined with PRP implantation. There were 50 cases (80 hips) in the control group, including 27 males and 23 females, aged 20 to 63 (45.72± 7.43) years, and the course of disease was 6 to 19 (14.9±3.8) months. Hip X-ay film was followed up after operation. Harris score and VAS score were used to evaluate the curative effect, and the survival rate of hip joint was recorded.@*RESULTS@#All patients had good wound healing, no infection, thrombosis and other complications. All patients were followed up for 12 to 14 (12.0±0.4) months. Twelve months after operation, the image expression of PRP group was better than that of control group(@*CONCLUSION@#Platelet-rich plasma(PRP) combined with artificialbone for core decompression and bone grafting can change the situation of simple artificial bone implantation and uncertain curative effect, improve the success rate of this operation, effectively reduce the collapse rate of femoral head necrosis in the early and middle stage, delay or even avoid hip replacement.

BMAL1 regulates mitochondrial fission and mitophagy through mitochondrial protein BNIP3 and is critical in the development of dilated cardiomyopathy

Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.