Toxicokinetics of MDMA and Its Metabolite MDA in Rats / 法医学杂志

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Physical factors promote osteogenic differentiation of stem cells / 中国组织工程研究

BACKGROUND:In response to the limitations of traditional repair methods for bone defects,stem cells are widely used in the research of regenerative medicine.Chemical factors are the current research hotspots,but recent studies confirm that the application of physical factors to regulate stem cell differentiation at home and abroad has been intensifying,and physical factors combined with biological scaffolds in bone tissue engineering provide a new idea and method for solving the difficult problem of bone defect repair,with good development prospects. OBJECTIVE:To summarize the molecular mechanisms of physical factors such as electromagnetic fields and ultrasound on osteogenic differentiation of stem cells as well as the regulation of signaling pathways and the feasibility of their application in bone tissue engineering. METHODS:A computerized search of the CNKI and PubMed for the last 20 years was conducted.In the title and abstract,we used"stem cell,bone defect,osteogenic differentiation,electromagnetic fields,ultrasound,shock wave,low-level laser therapy,mechanical force,bone tissue engineering"in Chinese and"stem cell,osteoporosis,osteogenic differentiation,electromagnetic fields,ultrasound,bone tissue engineering"in English as search terms.A total of 94 relevant articles were included for review. RESULTS AND CONCLUSION:(1)As a non-invasive,non-contact adjuvant therapy,physical factors have a significant impact on bone tissue engineering,and have a positive effect on regulating osteogenic differentiation of stem cells,promoting cell proliferation and viability in bone engineering scaffolds.(2)In addition to activating signaling pathways and osteogenic gene transcription,physical factors can also improve vascularization,increase the volume,area and thickness of bone formed in the stent,promote osseointegration,and improve the success rate of bone scaffolds in regenerating healthy bone tissue.(3)However,the use of physical factors for bone tissue engineering uses different experimental conditions,such as scaffold type,cell type,and intervention conditions,and cannot be directly compared to determine the best parameter settings.There is also a lack of consistency in the effectiveness of these different interventions in promoting fracture healing in clinical use.Therefore,it is necessary to further determine the optimal parameters of physical factors for bone tissue engineering in the future.(4)In general,as an ideal adjuvant therapy,physical factors have great potential in combining with various biomaterials and applying them in bone tissue engineering.

Photobiomodulation-induced osteogenic differentiation of mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Mesenchymal stem cells are pluripotent stromal cells isolated from a variety of tissues,which can differentiate into osteoblasts under certain conditions.Photobiomodulation,as an external stimulus,can promote osteogenic differentiation combined with other inducers or alone,providing new ideas for solving a series of bone diseases. OBJECTIVE:To review the relevant literature and mechanisms of photobiomodulation-induced osteogenic differentiation of mesenchymal stem cells,which will lay a theoretical foundation for bone tissue engineering using mesenchymal stem cells as seed cells and may offer some suggestions for future studies. METHODS:Relevant articles were searched on CNKI,PubMed and Wed of Science databases with Chinese search terms of"photobiomodulation,low power laser,low level laser,light-emitting diode,mesenchymal stem cells,osteogenic differentiation,biomaterials"and English search terms of"photobiomodulation,low level laser(light),light-emitting diode(LED),mesenchymal stem cell,osteogenic differentiation,biomaterials".Finally,88 articles were included for analysis. RESULTS AND CONCLUSION:(1)Photobiomodulation represented by low level laser and diode laser has a positive effect on promoting the proliferation and differentiation of mesenchymal stem cells.(2)Photobiomodulation can induce osteogenic differentiation of mesenchymal stem cells,whose feasibility has been verified in cell and animal experiments.On one hand,photobiomodulation can promote the expansion and differentiation of stem cells in vitro by activating related signaling pathways and up-regulating the expression of osteogenic molecules.On the other hand,photobiomodulation can improve the survival rate of stem cells in vivo,promote homing effect and shorten the healing time of bone defects after stem cells are injected into the body.However,photobiomodulation has a biphasic dose effect,whose laser parameters,experimental environment,cell type and other factors in various studies are different,making the research results lack consistency and difficult to apply in the clinic.(3)Combined with biological materials,other physical factors and drugs,photobiomodulation can also accelerate osteogenic differentiation.(4)In conclusion,photobiomodulation has been used increasingly widely in the medical field with its advantages of non-invasive,efficient and less-side reactions,and its role in bone tissue engineering has gradually become prominent,which provides a new method for the treatment of bone defects and related diseases.Further exploration should be focused on the standardized treatment parameters of photobiomodulation.

Experimental study on pharmacodynamics of Su Bei Zhi Ke granules (SBZKG) for acute tracheobronchitis / 中国临床药理学与治疗学

AIM: To observe the effect of Su Bei Zhi Ke granules (SBZKG) on acute tracheobronchitis (Syndrome of Wind-cold Attacking Lung). METHODS: Mouse ear swelling experiment and mouse abdominal capillary permeability experiment was used to observe its anti-inflammatory effect. Cough test in mice induced by ammonia water, and phlegm test in rats were used to observe the expectorant and antitussive effects of phenol red test in mice. We used the mortality rate experiment of infected mice to observe its antibacterial and antiviral effects. RESULTS: Compared with the contral group, the large and medium dose groups of SBZKG both reduced mouse auricle swelling (P<0.05) and increased swelling inhibition rate, reducing mouse abdominal capillary permeability (P<0.05, P<0.01). SBZKG can increase the phenol red sputum output in the respiratory tract of mice (P<0.01), prolong the cough incubation period of mice, reduce the number of coughs in mice (P<0.05, P<0.01), and increase the sputum output in rats (P<0.05, P<0.01). SBZKG can reduce the mortality rate of mice infected with bacteria and viruses. CONCLUSION: SBZKG has certain anti-inflammatory, antitussive, expectorant, antibacterial and antiviral effects, and has certain therapeutic effects on acute tracheobronchitis.

Growth Differentiation Factor 5 and Metabolic Diseases / 生物化学与生物物理进展

Growth/differentiation factor-5 (GDF-5) belongs to transforming growth factor-β (TGF-β) family, which is expressed in bone, cartilage, heart, brain, kidney, skeletal muscle and tendon, liver, fat and other organs and tissues as well. GDF-5 binds to receptor BMPR-I/BMPR-II and activates different signaling pathways such as smad1/5/8, PI3K/Akt, p38-MAPK. For a long time, numerous studies have shown that GDF-5 plays an important role in protecting joints. However, researchers have found GDF-5 also plays significant biological functions in other organs. For example, GDF-5 improves cardiac function by reducing oxidative stress and fibrosis in infarcted hearts. GDF-5 can also reduce oxidative stress in the brain and increase the number of neurons in effort to delay the progression of Alzheimer’s disease and Parkinson’s disease. It is a situation, research on GDF-5, at present, mainly focuses on the growth and repair of bone, cartilage and tendons, while there are few reports on its biological effects in other organs. Therefore, this article reviews and summarizes the research progress on GDF-5 and metabolic diseases in recent years in order to provide new insights and theoretical basis for the role of GDF-5 in improving metabolic diseases.

Application of multimodal ultrasound in large craniotomy for patients with severe traumatic brain injury: research progress / 中华创伤杂志

With the progression of primary and secondary brain injury, as well as the increase of the intracranial pressure, severe traumatic brain injury (sTBI) patients, if not timely and effective treated, will lead to brain hernia or even central failure. Therefore, sTBI patients often require emergency surgical intervention, including large craniotomy or even decompression. However, postural changes, brain tissue pulling and loss of cerebrospinal fluid can cause "brain drift" in sTBI patients. Meanwhile, improper rapid decompression will result in brain tissue displacement or delayed hematoma, which makes the intracranial condition deviated from the preoperative image data, even leads to deterioration. The application of multimodal intraoperative ultrasound can simply, intuitively visualize the intracranial lesion, blood flow and microperfusion in a real-time manner, guiding the surgeon to preserve the normal brain tissue to the maximum extent and improving the prognosis of the patients with the appropriate operation plan. Over the last few decades, the application of multimodal ultrasound in large craniotomy in patients with sTBI was mainly to identify intracranial lesions while there were few studies on the evaluation of cerebral hemodynamic heterogeneity of sTBI. To this end, the authors reviewed the imaging characteristics of various examination techniques of multimodal ultrasound and the progress of its application in sTBI surgery, hoping to provide evidences for accurate intraoperative evaluation and adjustment of treatment plan.

Clinicopathologic features and prognosis of young renal tumors with tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To retrospectively analyze clinical data of patients under 40 years old who underwent surgical treatment for renal tumors with tumor thrombus from January 2016 to December 2022 at Peking University Third Hospital, and to evaluate the surgical effect and investigate the relationship between clinicopathological characteristics and prognosis.@*METHODS@#The clinical data of 17 young patients with renal tumor thrombus were retrospectively analyzed, and the clinicopathological features and prognosis were summarized. The patients were grouped according to the presence or absence of symptoms, 2017 American Joint Committee on Cancer (AJCC) clinical stage, and postoperative combined adjuvant therapy. Kaplan-Meier method was used to plot the survival curve, and Log-rank test was used to compare the differences in postoperative survival time and progression-free survival time between the different groups. The relationship between clinicopathological features and prognosis was analyzed.@*RESULTS@#All the 17 patients received venous tumor thrombectomy, including 16 patients (94.1%) who underwent radical nephrectomy and 1 patient (5.9%) who underwent partial nephrectomy. Twelve patients (70.6%) had symptoms and 5 (29.4%) had no symptoms before operation. A total of 17 renal tumors were observed, with 2 patients (11.8%) identified as benign and 15 patients (88.2%) classified as malignant. Among the malignant tumors, 1 patient (6.7%) was diagnosed as clear cell carcinoma, while the remaining 14 patients (93.3%) were categorized as non-clear cell carcinoma. In terms of tumor stage, 8 patients (53.3%) were classified as stage Ⅲ according to the AJCC classification, while 7 patients (46.7%) were categorized as stage Ⅳ. Additionally, 6 patients (40%) received multiple adjuvant therapy, while 9 patients (60%) did not undergo such treatment. The follow-up period ranged from 2 to 78 months, with a median follow-up of 41 months. During this time, 3 patients (20%) died. The median survival time after surgery was 39.0 (2.3, 77.8) months, and the progression-free survival time was 16.4 (2.3, 77.8) months. There was no significant difference in postoperative survival time and progression-free survival time among young patients with renal tumor with tumor thrombus, based on the presence of symptoms before surgery (P=0.307, P=0.302), clinical stage of AJCC (P=0.340, P=0.492), and postoperative adjuvant therapy (P=0.459, P=0.253) group.@*CONCLUSION@#The pathological types of young patients with renal tumor with tumor thrombus are more complex and varied due to symptoms, and the proportion of non-clear cell carcinoma in malignant tumor with tumor thrombus is higher. Symptomatic and non-clear cell carcinoma may be potentially associated with poor prognosis. Surgical operation combined with adjuvant therapy is a relatively safe and effective treatment for young patients with renal tumor and tumor thrombus.

Risk factors for massive hemorrhage after radical nephrectomy and removal of venous tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus.@*METHODS@#From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant.@*RESULTS@#Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003).@*CONCLUSION@#Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.

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

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

Experience in the treatment of urethral injuries due to old pelvic fractures in girls / 中华泌尿外科杂志

Objective:To discuss the treatment methods for old pelvic fractures and urethral injuries in young girls.Methods:We retrospectively analyzed the clinical data of 10 girls, mean age of(8.5±4.3)years with old pelvic fractures and urethral injuries treated with different surgical methods in our hospital from April 2015 to April 2023. 7 cases were complicated with urethrovaginal fistula, 1 case was complicated with vesicovaginal fistula; 5 patients had distal urethral atresia or stenosis; 5 cases complicated with vaginal stenosis or partial atresia. One case underwent repair of urethrovaginal fistula via transpertoineal approach, two cases underwent urethral anastomosis (end to end anastomosis) via transpubic approach, one case underwent repair of urethrovaginal fistula and bladder neck urethral anastomosis via transpubic approach, four cases underwent urethroplasty repair of urethrovaginal fistula and bladder neck reconstruction surgery, one underwent urethroplasty and bladder neck reconstruction surgery via transpubic approach, one underwent augmented enterocystoplasty and continent urinary diversion by using the appendix. Observe the urination condition after operation (Urinary incontinence is defined as the use of more than 1 piece of urine pad per day, good urination is defined as the use of ≤ 1 piece of urine pad per day, and dysuria is defined as the complaint of laborious urination, and the maximum urine flow rate is less than 10 ml/s).Results:All surgeries were successfully completed without complications such as wound infection or tissue necrosis.The postoperative follow-up time was (52.0±26.2) months. 2 cases achieved good continence and no dysuria.Postoperative complications occurred in 7 cases, of which 2 cases had dysuria due to urethral stricture and improved after urethral dilatation; 5 cases of urethrovaginal fistula recurred, of which 3 cases had undergone rerepair surgery, and 2 of them achieved good urinary control without dysuria. One case with enterocystoplasty and contiunent urinary diversion recovered well after surgery.Conclusions:The management of old pelvic fractures and urethral injuries in girls is complicated, with a high rate of postoperative complications. It is necessary to choose appropriate treatment methods based on age, severity of the lesion, and urethral and vaginal conditions.

Development of needle-thread integrative embedding needle / 中国针灸

The needle-thread integrative embedding needle consists of needle handle, needle core, thread, locker and needle guard. The thread is fixed in the core by the locker. With the needle inserted into acupoint, the locker is separated from the thread, while the thread is embedded directly into acupoint, to achieve one acupoint with one needle. This type of thread embedding needle is operated simply and safely without cross infection occurrence, easy to carry.

Progress on the role of Kalirin-7 in exercise intervention-mediated improvement of neurodegenerative diseases / 生理学报

Guanine nucleotide exchange factor Kalirin-7 (Kal-7) is a key factor in synaptic plasticity and plays an important regulatory role in the brain. Abnormal synaptic function leads to the weakening of cognitive functions such as learning and memory, accompanied by abnormal expression of Kal-7, which in turn induces a variety of neurodegenerative diseases. Exercise can upregulate the expression of Kal-7 in related brain regions to alleviate neurodegenerative diseases. By reviewing the literature on Kal-7 and neurodegenerative diseases, as well as the research progress of exercise intervention, this paper summarizes the role and possible mechanism of Kal-7 in the improvement of neurodegenerative diseases by exercise and provides a new rationale for the basic and clinical research on the prevention and treatment of neurodegenerative diseases by exercise.

Current diagnosis and treatment of skull base osteomyelitis / 临床耳鼻咽喉头颈外科杂志

Skull base osteomyelitis is a rare, refractory, and potentially fatal disease primarily caused by otogenic and sino rhinogenic infections. At times, it can mimic neoplasia complicating the diagnosis. With the use of antibiotics, advancements in diagnostic methods, and skull base surgical techniques, the mortality rate has significantly improved. However, the successful diagnosis and treatment of the disease is still challenging due to delayed diagnosis, lengthy treatment course, a tendency for relapse and lack of guidelines. Therefore, this article aims to review the progress in the diagnosis and treatment of skull base osteomyelitis.

Hsa_circ_0000392 affects the radiation sensitivity of cervical cancer by targeting the miR-145-5p/CRKL/MAPK pathway / 中华肿瘤杂志

Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.

Hsa_circ_0000392 affects the radiation sensitivity of cervical cancer by targeting the miR-145-5p/CRKL/MAPK pathway / 中华肿瘤杂志

Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.

Diagnosis and treatment of nephroblastoma with WAGR syndrome / 中华泌尿外科杂志

Objective:To discuss the diagnosis and treatment 0f WAGR syndrome.Methods:The clinical data of 10 cases of WAGR syndrome children admitted to our hospital from January 2008 to November 2019 were respectively analyzed including the clinical features, diagnosis, and surgical treatments. There were 6 males and 4 females, aged from 13 to 36 months, with an average of 23.6 months. 9 cases were diagnosed as iris absence due to ocular abnormalities in infancy, and 1 case was diagnosed as iris absence due to ocular abnormalities by physical examination because of renal mass. There were 2 boys with cryptorchidism, and 2 boys with hypospadias, 1 of which did not received operation because of mild hypospadias, and another undergoing surgery. There were no abnormality of genitourinary system in the remaining 5 cases. There were 7 cases of unilateral nephroblastoma, with 1 case at the left and 6 cases at the right, and there were 3 cases of bilateral nephroblastoma. Abdominal doppler ultrasound and enhanced abdominal CT were performed for all patients. Abdominal doppler ultrasound indicated solid mass in renal parenchyma or non-uniform echo zone. Abdominal enhanced CT indicated renal tumor with diameter of 1.8 cm-12.7 cm and locally non-uniform enhanced echo. Among the 7 cases of unilateral nephroblastoma, 4 underwent nephrectomy, 1 underwent tumor enucleation, and 2 underwent tumor enucleation for unilateral tumor complicated with nephrogenic rests. There were 3 cases of bilateral nephroblastoma, 2 cases undergoing unilateral tumor enucleation firstly and contralateral tumor enucleation following chemotherapy. One case underwent unilateral tumor nephrectomy followed by contralateral tumor enucleation. One case of unilateral nephrogenic rests did not undergo renal tumor surgery. Preoperative chemotherapy was performed in 7 patients, including 3 bilateral nephroblastoma, 1 unilateral nephroblastoma combined with contralateral nephroblastoma, and 3 unilateral tumors larger enough to pass the midline. The chemotherapy regimen was VCR+ ACTD in 5 cases, VCR+ ACTD+ CTX+ DOX/CDDP+ VP16 and VCR+ CTX+ DOX in another 2 cases respectively.Results:All 10 cases were diagnosed as nephroblastoma. There were 3 patients without preoperative chemotherapy which belongs to COG stageⅠ(1 case) and STAGEⅢ(2 cases); Preoperative chemotherapy was performed in 2 patients with SIOP stage Ⅱ, 2 patients with SIOP stage Ⅲ, and 3 patients with SIOP stageⅤ. Nine children received regular chemotherapy after surgery, among which 1 child in stage Ⅰ received DD4A chemotherapy regimens, 2 children in stage Ⅱ received DD4A and EE4A regimen respectively, and 3 of the 4 children in stage Ⅲ received regular chemotherapy after surgery, including EE4A(1 case)and DD4A(2 cases). EE4A(1 case)and DD4A(2 cases) chemotherapy were performed in 3 patients with stage Ⅴ according to their unilateral tumor stage. Ten cases were followed up, with 9 of the 10 cases having no tumor recurrence or metastasis, and death in 1 case. At present, abdominal doppler ultrasound of 1 child with nephrogenic rests showed no obvious progress. The renal function of 9 children was not significantly abnormal during the regular follow-up. The results of intelligence screening showed that 6 of the 10 patients were significantly behind their peers, and 4 had no obvious abnormality compared with their peers. Gene tests were performed 3 times after surgery, and the results showed the deletion of 11p13 and adjacent distal genes.Conclusions:WAGR syndrome is rare in clinical practice, and renal ultrasound should be monitored after diagnosis to detect renal tumors in early stage. For bilateral cases, renal function should be preserved as long as possible in order to reduce the probability of renal failure. Long-term follow-up of nephroblastoma with this syndrome is particularly important.

Chemical genetics technology regulates the activity of GLP-1 neurons and its effect on appetite / 中华内分泌代谢杂志

Objective:To conduct a glucagon like peptide-1(GLP-1)controllability model rat by chemical genetics, and observe the impact of GLP-1 neuron excitability on appetite.Methods:Fifteen rats were evenly divided into Green fluorescent protein(GFP)group, HM3D group, and HM4D group. Various combinations of adeno-associated virus(rAAV)were injected into the nucleus tractus solitarius(NTS). rAAV-GLP-1-cre and rAAV-GFP-dio were administered in rats of GFP group. The rats of HM3D group were injected with rAAV-GLP-1-cre and rAAV-HM3D-mCherry-dio while rAAV-GLP-1-cre and rAAV-HM4D-mCherry-dio were injected in rats of HM4D group . The optimal dose of clozapine N-oxide(CNO)was selected based on feeding behavior and body weight changes of rats after intraperitoneal injection of different doses of CNO. The controllability of GLP-1 neurons was confirmed by comparing with intraperitoneal injection of saline. The number of activated GLP-1 neurons in the NTS area and the expression of POMC neurons in the hypothalamus were detected 30 minutes after CNO injection.Results:GLP-1 neurons in the NTS area of rats were successfully labeled. The rat of HM3D group revealed a decrease in food intake( P=0.021)while the rat of HM4D group showed an increase( P=0.002), when given 1 mg/kg of CNO, no changes at the dose of 0.5 mg/kg and 3.0 mg/kg. Immunofluorescence showed that the activity of GLP-1 neurons in NTS of GFP group was lower than that of HM3D group( P=0.022), and higher compared with that of the HM4D group( P=0.049). The expression of GLP-1 neurons in NTS and POMC neurons in the hypothalamus of the HM3D group after intraperitoneal injection of CNO was also higher than that in the HM4D group( P=0.003). Conclusion:Using chemical genetics technology, GLP-1 controllability model rat could be successfully established via injecting varying combinations of rAAV into the NTS area of rat. Injection of 1 mg/kg CNO can effectively activate or inhibit the neuron to regulate appetite.

Effect of lncRNA SNHG6 targeting miR-485-3p on proliferation and radiotherapy sensitivity of cervical cancer SiHa cells / 中华放射肿瘤学杂志

Objective:To investigate the effect of lncRNA SNHG6 on the proliferation and radiotherapy sensitivity of cervical cancer SiHa cells and its potential mechanism.Methods:The expression levels of lncRNA SNHG6 and miR-485-3p in cervical cancer tissues, paracancer tissues, SiHa cells and SiHa cells exposed to X-ray were detected. The relationship between lncRNA SNHG6 and miR-485-3p was analyzed. After overexpression or knockdown of SNHG6 and miR-485-3p, cell proliferation ability, number of invasion and apoptosis rate were determined by MTT, Transwell chamber assay and flow cytometry, respectively. The effect of miR-485-3p on the Wnt/β-catenin pathway and the effect of XAV939 on SiHa cell proliferation and radiation sensitivity were analyzed.Results:lncRNA SNHG6 was highly expressed in cervical cancer tissues and SiHa cells, whereas was lowly expressed in X-ray irradiated SiHa cells. miR-485-3p was lowly expressed in cervical cancer tissues and SiHa cells, whereas was highly expressed in X-ray irradiated SiHa cells. lncRNA SNHG6 targeted miR-485-3p. Down-regulation of lncRNA SNHG6 expression inhibited cell proliferation and invasion, and enhanced its sensitivity to X-ray radiotherapy, while miR-485-3p inhibitor transfected cells exerted the opposite effect. The up-regulation of lncRNA SNHG6 promoted the proliferation and invasion of SiHa cells through miR-485-3p, and reduced the sensitivity of radiotherapy. Down-regulation of miR-485-3p activated the Wnt/β-catenin pathway, promoted cell proliferation and invasion of SiHa, and reduced its radiation sensitivity to X-ray.Conclusion:Overexpression of lncRNA SNHG6 targeting miR-485-3p activates the Wnt/β-catenin pathway to regulate the proliferation and radiotherapy sensitivity of SiHa cells.

Bladder-sparing treatment following noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Application status and prospect of single-cone obturation technique with bioceramic sealers / 中华口腔医学杂志

Compared with cold lateral condensation and continuous wave of condensation which are classically used in clinical, newly emerging single-cone obturation technique is easy-to-operate as well as time-saving. Especially when combined with bioceramic root canal sealers of improved physicochemical and biological properties, single-cone obturation technique showed satisfactory short-term outcomes in clinical observations. However, difficulties still exist in avoiding the root canal overfilling and in operating the retreatment. Besides, the long-term effects of single-cone obturation with bioceramic sealers still remain unclear. This article makes an overview on the history and development of single-cone obturation ,and provides analysis of its pros and corns. Furthermore, we would also like to summarize its clinical application and look into its future improvements.