Molecular Mechanism and Structure-activity Relationship of the Inhibition Effect between Monoamine Oxidase and Selegiline Analogues.

INTRODUCTION: To investigate the inhibition properties and structure-activity relationship between monoamine oxidase (MAO) and selected monoamine oxidase inhibitors (MAOIs, including selegiline, rasagiline and clorgiline). METHODS: The inhibition effect and molecular mechanism between MAO and MAOIs were identified via the half maximal inhibitory concentration (IC50) and molecular docking technology. RESULTS: It was indicated that selegiline and rasagiline were MAO B inhibitors, but clorgiline was MAO-A inhibitor based on the selectivity index (SI) of MAOIs (0.000264, 0.0197 and 14607.143 for selegiline, rasagiline and clorgiline, respectively). The high-frequency amino acid residues of the MAOIs and MAO were Ser24, Arg51, Tyr69 and Tyr407 for MAO-A and Arg42 and Tyr435 for MAO B. The MAOIs and MAO A/B pharmacophores included the aromatic core, hydrogen bond acceptor, hydrogen bond donor-acceptor and hydrophobic core. CONCLUSION: This study shows the inhibition effect and molecular mechanism between MAO and MAOIs and provides valuable findings on the design and treatment of Alzheimer's and Parkinson's diseases.

A case of death in children with hypereosinophilia complicated with Loffler endocarditis / 中国综合临床

Objective:To investigate the clinical features of hypereosinophilia (HE) complicated with Loffler endocarditis in children, in order to analyze the etiology, clinical stage and prognosis of HE complicated with Loffler endocarditis.Methods:A case of childhood hypereosinophilia complicated with Loffler endocarditis diagnosed and treated in the Second Hospital of Hebei Medical University was analyzed retrospectively, and its clinical characteristics, causes and clinical stages were analyzed.Results:In this study, the patient was a young male. He had diarrhea for more than 40 days due to intermittent abdominal pain, dyspnea for 10 days, and poor food intake for 3 days. The blood routine showed that he was HE. The ultrasound showed Loffler endocarditis. The child had severe heart failure and multiple organ functions were involved. After active treatment, he still had multiple organ failure, and finally died of multiple organ failure and ventricular fibrillation.Conclusion:Loffler endocarditis is a serious complication of HE, with low morbidity and rare clinical manifestations. Early intervention can reduce mortality.

Effects of FAC combined with Bu conditioning for SAA patients undergoing allogeneic stem cell transplantation / 西安交通大学学报(医学版)

【Objective】 To observe the effects of FAC combined with Bu conditioning for severe aplastic anemia (SAA) patients undergoing allogeneic hematopoietic stem cell transplantation. 【Methods】 The data of 28 SAA patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital from January 2016 to September 2021 were collected and analyzed. The patients were divided into two groups: FAC conditioning group and FAC + Bu conditioning group. We observed the side effects of conditioning regimen, hematopoietic recovery, acute and chronic graft versus host disease (GVHD), viral infection, incidence of venous obstructive disease (VOD), progression free survival (PFS), and overall survival (OS). 【Results】 There was no significant difference between the two groups in age, gender, physical condition, history of disease, gender relationship between donors and recipients, transplantation type, infusion of bone marrow nucleated cells, MNC or CD34 positive cells (P>0.05). Compared with those in FAC group, the side effects of auditory hallucination and visual hallucination in FAC + Bu group increased, the incidence of mixed chimerism decreased, the time of platelet reconstruction shortened, the incidence of grade Ⅲ-Ⅳ aGVHD increased. However, 3-year PFS or OS did not significantly differ between the two groups. 【Conclusion】 FAC combined with Bu conditioning regimen promotes implantation and reduces mixed chimerism. However, it does not improve patients’ overall survival.

Preliminary exploration on operation process for autologous ozonized blood transfusion / 中国输血杂志

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Weakly supervised multitask learning models to identify symptom onset time of unclear-onset intracerebral hemorrhage.

BACKGROUND: Approximately one-third of spontaneous intracerebral hemorrhage patients did not know the onset time and were excluded from studies about time-dependent treatments for hyperacute spontaneous intracerebral hemorrhage. AIMS: To help clinicians explore the benefit of time-dependent treatments for unclear-onset patients, we presented artificial intelligence models to identify onset time using non-contrast computed tomography (NCCT) based on weakly supervised multitask learning (WS-MTL) structure. METHODS: The patients with reliable symptom onset time (strong label) or repeat CT (weak label) were included and split into training set and test set (internal and external). The WS-MTL structure utilized strong and weak labels simultaneously to improve performance. The models included three binary classification models for classifying whether NCCT acquired within 6, 8 or 12 h for different treatments measured by area under curve, and a regression model for determining the exact onset time measured by mean absolute error. The generalizability of models was also explored in comprehensive analysis. RESULTS: A total of 4004 patients with 10,780 NCCT scans were included. The performance of WS-MTL classification model showed high accuracy, and that of regression model was satisfactory in ≤6 h subgroup. In comprehensive analysis, the WS-MTL showed better performance for larger hematomas and thinner scans. And the performance improved effectively as training amounts increasing and could be improved steadily through retraining. CONCLUSIONS: The WS-MTL models showed good performance and generalizability. Considering the large number of unclear-onset spontaneous intracerebral hemorrhage patients, it may be worth to integrate the WS-MTL model into clinical practice to identify the onset time.

Site-specific O-glycosylation analysis of SARS-CoV-2 spike protein produced in insect and human cells

Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures. SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported. The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence difficult to predict. Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S - insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD). In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD. Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites. However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy. This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.

The Patterns of Morphological Change During Intracerebral Hemorrhage Expansion: A Multicenter Retrospective Cohort Study.

Objectives: Hemorrhage expansion (HE) is a common and serious condition in patients with intracerebral hemorrhage (ICH). In contrast to the volume changes, little is known about the morphological changes that occur during HE. We developed a novel method to explore the patterns of morphological change and investigate the clinical significance of this change in ICH patients. Methods: The morphological changes in the hematomas of ICH patients with available paired non-contrast CT data were described in quantitative terms, including the diameters of each hematoma in three dimensions, the longitudinal axis type, the surface regularity (SR) index, the length and direction changes of the diameters, and the distance and direction of movement of the center of the hematoma. The patterns were explored by descriptive analysis and difference analysis in subgroups. We also established a prognostic nomogram model for poor outcomes in ICH patients using both morphological changes and clinical parameters. Results: A total of 1,094 eligible patients from four medical centers met the inclusion criteria. In 266 (24.3%) cases, the hematomas enlarged; the median absolute increase in volume was 14.0 [interquartile range (IQR), 17.9] mL. The initial hematomas tended to have a more irregular shape, reflected by a larger surface regularity index, than the developed hematomas. In subtentorial and deep supratentorial hematomas, the center moved in the direction of gravity. The distance of center movement and the length changes of the diameters were small, with median values of less than 4 mm. The most common longitudinal axis type was anterior-posterior (64.7%), and the axis type did not change between initial and repeat imaging in most patients (95.2%). A prognostic nomogram model including lateral expansion, a parameter of morphological change, showed good performance in predicting poor clinical outcomes in ICH patients. Conclusions: The present study provides a morphological perspective on HE using a novel automatic approach. We identified certain patterns of morphological change in HE, and we believe that some morphological change parameters could help physicians predict the prognosis of ICH patients.

Isokinetic evaluation of muscle strength and endurance after treatment of acute Achilles tendon rupture using a tunnel beneath paratenon / 中华创伤骨科杂志

Objective:To use an isokinetic test to objectively evaluate the recovery of muscle strength and endurance after treatment of acute Achilles tendon rupture using a tunnel beneath paratenon.Methods:A retrospective study was conducted of the 23 patients who had been treated at Department of Orthopedics, The Forth Medical Center, General Hospital of Chinese PLA by a tunnel beneath paratenon for acute Achilles tendon rupture from January 2017 to January 2018. They were 22 males and one female, aged from 26 to 60 years (average, 35.7 years), with 11 right and 12 left sides involved. Surgery was performed 0.5 to 7.0 days (average, 2.7 days) after injury. Length of incision, skin necrosis, infection, re-rupture, ankle-hindfoot score of American Orthopedic Foot & Ankle Society (AOFAS) and Achilles tendon total rupture scores (ATRS) were followed up for 18 months. Surgical outcomes were objectively evaluated by an isokinetic test to compare the recovery of muscle strength and endurance between the affected and normal sides.Results:Skin necrosis, infection or re-rupture occurred in none of the patients. Incision length averaged 1.4 cm (from 1 to 2 cm), AOFAS 99.1 (from 93 to 100, giving an excellent and good rate of 100%), and ATRS 97.0 (from 88 to 100). Isokinetic evaluation showed that the peak torques of ankle plantar flexion and dorsal extension at 5 test speeds (30°/s, 60°/s, 90°/s, 120°/s and 240°/s) were not significantly different between the affected and normal sides ( P>0.05). In the endurance test, the total work of ankle plantar flexion was (691.2±258.8) J on the normal side and (670.6±304.2) J on the affected side, showing no significant difference between the 2 sides ( P>0.05); the total work of ankle dorsal extension at the normal side was (407.3±119.2) J, significantly larger than that at the affected side [(362.2±117.5) J] ( P=0.001). Conclusion:An isokinetic test can be used to objectively evaluate the recovery of muscle strength and endurance after treatment of acute Achilles tendon rupture using a tunnel beneath paratenon.

Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate

Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. Interestingly, we also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.

Evolution and molecular characteristics of SARS-CoV-2 genome

ObjectivesTo reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. MethodsVarious evolution analysis methods were employed. ResultsThe estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). ConclusionsIn this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2.

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Single-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment in normal stomach (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.

Effects of cattle encephalon glycoside and ignotin on the expression of glial fibrillary acidic protein and neuronal nuclear antigen in the brain of the APP/PS1 mouse models of Alzheimer's disease / 中华老年医学杂志

Objective:To investigate the effects of cattle encephalon glycoside and ignotin(CEGI)on the expression of glial fibrillary acidic protein(GFAP)and neuronal nuclear antigen(NeuN)in the brain of APP/PS1 model mice of Alzheimer's disease.Methods:A total of 36 5-month-old APP/PS1 dual-transgenic model mice were randomly divided into 3 groups: the model group(normal saline 6.6 ml·kg -1·d -1), CEGI group(CEGI 6.6 ml·kg -1·d -1)and donepezil group(donepezil 2 mg·kg -1·d -1), with 12 in each group.Twelve C57BL/6J mice of the same age were used as the normal control group.All mice were given drugs for 6 weeks consecutively.Brain tissue was collected for immunohistochemical staining to detect the expression of amyloid β-protein(Aβ), GFAP and NeuN, which were then analyzed quantitatively. Results:The results of immunohistochemical staining indicated that levels of Aβ and GFAP were higher and levels of NeuN were lower in the model group than in the normal control group(0.147±0.068% vs.0%, 61.750±22.020 vs.26.000±4.598, 0.021±0.002 vs.0.032±0.003, P<0.05). Levels of Aβ and GFAP were lower and levels of NeuN were higher in the CEGI group and the donepezil group than in the model group(0.058±0.055 % vs.0.057±0.045 %, 38.250±5.418 vs.36.130±5.963, 0.029±0.004 vs.0.027±0.003, P<0.05). There was no significant difference in the expression of Aβ, GFAP and NeuN between the CEGI group and the donepezil group( P>0.05). Conclusions:CEGI has multi-target neuroprotective effects via down-regulating the expression of Aβ and GFAP and up-regulating the expression of NeuN.

Optimal preoperative timing of indocyanine green administration for laparoscopic cholecystectomy under fluorescence navigation / 中华肝胆外科杂志

Objective:To analyze the optimal preoperative timing of indocyanine green administration to do the fluorescence imaging during laparoscopic cholecystectomy.Methods:A total of 102 patients with laparoscopic cholecystectomy from January 2019 to November 2019 were retrospectively analyzed in this study, including 42 male patients and 60 female patients with an average age of 49(15-87) years old. The preoperative timing of indocyanine green (2.5 mg/ml, 1 ml) administration was set at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 h before surgery, 12, 7, 8, 6, 6, 7, 8, 10, 8, 8, 8, 7, 7 patients, respectively. The intraoperative fluorescence imaging and signal contrast were compared.Results:Comparing with 0.5h group, the liver fluorescence intensities in 5, 6, 7, 8, 9, 10, 11 and12 h groups were significantly decreased (all P<0.05). There were no differences in the fluorescence intensities of the gallbladder, gallbladder duct, common bile duct and common liver duct between those groups with different injection timepoints (all P>0.05), and signal contrast was significantly lower in 0.5 h group than patients in 6, 7, 8, 9, 10, 11 and 12 h groups (all P<0.05). When preoperative timing of indocyanine green administration was 7 h, the fluorescence signal contrast reached the highest values of 0.29. Conclusions:The optimal preoperative timing of indocyanine green intravenous administration for laparoscopic cholecystectomy under fluorescence navigation was 7 h at dose 2.5 mg.

Application of decision tree method in evaluation of nursing workload in surgical departments / 中国实用护理杂志

Objective@#To evaluate the nursing workload in surgical departments by decision tree method.@*Methods@#The indexes of nursing workload of 23 surgical departments were analyzed with decision tree method from February 20 to March 26 in 2017.@*Results@#According to decision tree analysis, the number of admitted patients was high-priority variable (F=39.128, P=0.000), and the nursing workload was divided into four grades by number of admitted patients ≤ 1, 1<number of admitted patients ≤ 4, 4 < number of admitted patients ≤ 7, number of admitted patients >7, respectively. The suboptimal variables were number of operations (F=7.578, P=0.046) and number of electrocardiogram monitors used (F=28.306, P=0.000), the nursing workload was further divided into six grades by number of operations ≤ 5, number of operations>5 and number of electrocardiogram monitors use ≤ 5, number of electrocardiogram monitors use > 5, respectively.@*Conclusions@#The number of admitted patients, electrocardiogram monitors used and operative patients were significant indexes of nursing workload in surgical departments, which helps the nurse managers evaluate the nurse performance and optimize human resource allocation based on decision tree analysis and clinical practice.

Management of chronic Achilles tendon rupture of Myerson type Ⅱ using a tunnel beneath paratenon / 中华创伤骨科杂志

Objective To explore the clinical efficacy of using a tunnel beneath the paratenon to repair chronic Achilles tendon rupture of Myerson type Ⅱ.Methods From August 2008 through January 2018,19 patients with chronic Achilles tendon rupture were treated with a self-designed minimally invasive suture technique at Department of Orthopaedics,The Fourth Medical Center,General Hospital of PLA.They were all male,aged from 25 to 64 years(average,40.4 years).The left side was injured in 12 patients and the right side in 7.The duration from injury to surgery ranged from 28 to 120 days,averaging 60 days.The Achilles tendon defects averaged 3.84 cm.Their clinical diagnoses were confirmed by positive results of clinical examination and magnetic resonance imaging(MRI) scans.After a 2 cm transverse incision was made at the proximal side,the proximal stump beneath the paratenon was adequately released with a periosteum elevator.The proximal stump was sutured by the Bunnell method with an Ethicon-X519 non-absorbable suture under direct vision.After a 1.0-1.5 cm transverse incision was made,percutaneous Bunnell suture was performed at the distal side.The proximal stump was then introduced into the distal incision through the paratenon tunnel.After the affected foot was fully flexed,the 2 stumps were tied closely together and buried under direct vision.Early rehabilitation was encouraged after surgery.The clinical efficacy was assessed according to the ankle-hindfoot scores of American Orthopaedic Foot&Ankle Society(AOFAS) and the Arner-Lindholm evaluation criteria.Results The 19 patients were followed up for 10 months to 9.5 years(average,2.45 years).All the wounds healed at the first stage without any complications related to incision,sural nerve injury or tendon re-rupture.Their AOFAS ankle-hindfoot scores averaged 98.4,with 19 excellent cases;according to the Arner-Lindholm criteria,13 cases were excellent and 6 cases good.Both of the evaluation systems yielded a good to excellent rate of 100%.In the 3 patients who underwent isokinetic testing,there was no significant difference between the normal and affected sides in the peak value of flexion or in the total work of fatigue.Conclusion Using a tunnel beneath the paratenon is a good self-designed minimally invasive suture technique for chronic Achilles tendon rupture of Myerson type Ⅱ because it is simple and reliable,and leads to limited tissue damage,adhesion or complications.

Application of decision tree method in evaluation of nursing workload in surgical departments / 中国实用护理杂志

Objective To evaluate the nursing workload in surgical departments by decision tree method. Methods The indexes of nursing workload of 23 surgical departments were analyzed with decision tree method from February 20 to March 26 in 2017. Results According to decision tree analysis,the number of admitted patients was high-priority variable (F=39.128, P=0.000), and the nursing workload was divided into four grades by number of admitted patients ≤ 1, 1<number of admitted patients ≤ 4, 4 < number of admitted patients ≤ 7, number of admitted patients >7, respectively. The suboptimal variables were number of operations (F=7.578, P=0.046) and number of electrocardiogram monitors used (F=28.306, P=0.000), the nursing workload was further divided into six grades by number of operations ≤ 5,number of operations>5 and number of electrocardiogram monitors use ≤ 5,number of electrocardiogram monitors use > 5, respectively. Conclusions The number of admitted patients, electrocardiogram monitors used and operative patients were significant indexes of nursing workload in surgical departments, which helps the nurse managers evaluate the nurse performance and optimize human resource allocation based on decision tree analysis and clinical practice.

Research progress on palmitoylation of postsynaptic density protein 95 / 中华老年医学杂志

Postsynaptic density protein 95(PSD-95) ,the most abundant and significant synapse scaffolding protein at excitatory synapses ,is a hallmark of synaptic function. Proteins palmitoylation is one of the important post-translational modifications ,which is occurred more frequently in the nervous system than in other organs. Palmitoylation-dependent regulation of PSD-95 has become a research hotspot in the fields of neuroplasticity and neuropsychiatric diseases.

Preparation and Evaluation of Solid Lipid Nanoparticles Containing Ketoprofen / 中国药师

Objective:To prepare ketoprofen-loaded solid lipid nanoparticles ( SLN) and evaluate the properties. Methods: The formula was optimized by orthogonal experiments with the encapsulation efficiency as the index. The optimal preparation was investiga-ted by the morphology, particle size, zeta potential and drug forms. The release property was characterized by a dialysis method and the release process was fitted. Results: The best formula was as follows: poloxamer 0. 1g, Tween-800. 2g, lecithin 0. 15g, glycerol monostearate 0. 05g and ketoprofen 50mg. The particles were spherical in shape with the encapsulation efficiency of 61. 95%, the par-ticle size was 151. 7 nm and the zeta potential was-30. 2 mV. The result of DSC indicated the drug dispersed in the lipid matrix was a-morphous and molecular state. The in-vitro release curve showed the release was rapid at the early stage and then slowed down with the accumulated amount up to (85. 11 ± 7. 62)% in 12h. The drug was released slowly from SLN with the matrix erosion. The release pro-file fitted well with a Higuchi equation. Conclusion: The solid lipid nanoparticles containing ketoprofen exhibit good quality and the preparation method is simple and feasible, therefore, it is valuable to be further studied.

Transvaginal natural orifice transluminal endoscopic surgery in female urologic diseases / 中华泌尿外科杂志

Objective To describe our experience with the transvaginal natural orifice transluminal endoscopic surgery (NOTES) in female patients,and to evaluate its clinical value.Methods Between May 2010 and April 2017,a total of 289 female patients underwent transvaginal NOTES in our center,including 31cases of adrenal tumors,46 cases of renal tumors,188 cases of non-functional kidneys,5 cases of renal cysts,4 cases of duplex kidney,7 cases of renal tuberculosis and 8 cases of renal pelvis tumors.Among them,146 cases were on the left side,142 cases on the right side,and 1 case on both sides (renal cysts).The median age was 39.4 (range 23 to 76) years,and the median body mass index was 21.8(range 15.4 to 32.6) kg/m2.After general anesthesia,the patients were positioned in lithotomy with ipsilateral lumbar at 30°-60° angle to the floor.Hybrid and pure transvaginal NOTES were performed.The specimen was removed through an extended incision at the posterior vaginal fornix.Results Transvaginal NOTES was successfully completed in 281 patients.Two patients required conversion to suprapubic-assisted laparoendoscopic single-site surgery because of the rectal injury in pure transvaginal NOTES nephrectomy.Six patients underwent open conversion.The various transvaginal hybrid NOTES procedures included adrenalectomy (31 cases),nephrectomy (206 cases;simple 174 cases,radical 32 cases),partial nephrectomy (13 cases),heminephroureterctomy for duplex kidney (4 cases) and hybrid endoscopy for nephroureterectomy (7 cases).The mean operative time was 105 min (45-310 min),the mean estimated blood loss was 87 ml (20-800 ml),the mean visual analogue score (VAS) of 48 hours after operation was 2.5 (1-4) points and the mean hospitalization was 7.3 d (4-13 d) for transvaginal hybrid NOTES.The various pure transvaginal NOTES procedures included nephrectomy (22 cases;simple 21,radical 1),renal cyst excision (5 cases).The mean operative time was 170 min (60-320 min),the mean estimated blood loss was 140 ml (20-500 ml),the mean VAS of 48 hours after operation was 1.7 (1-3) points and the mean hospitalization was 5.5 d (3-10 d) for transvaginal pure NOTES.Complications occurred in 56 cases (19.38％),including 20 cases (6.92％) of severe complications,and no death occurred.After a mean follow-up of 51 (range 3 to 86) months,umbilicus scar was hidden.The incision in the vagina healed well.No infection in the abdominal or pelvic cavity or celiocele occurred.The umbilicus scar is not obvious after surgery,and 3 months after surgery.The median Patient Scar Assessment Questionnaire (PSAQ) score was 38 (31-58) and the median Female Sexual Function Index (FSFI) score was 28.2 (22.5-32.2),and the quality of life index was significantly higher than that of preoperation.Condusions Transvaginal NOTES could treat variousprimary diseases,and improve the postoperative quality of life.It does not increase the incidence of related complications,or cause negative effect on the female sexual function,pregnancy or fertility.It can lead to good cosmetic outcome and less pain,which is worth applying in clinical practice.

Preparation and Evaluation of pH-Sensitive Paclitaxel-loaded Copolymeric Micelles / 中国药师

Objective:To synthesize poly (2-ethyl-2-oxazoline)-poly(lactic acid) copolymer (PEOz-PLA), prepare pH-sensitive paclitaxel-loaded polymeric micelles, and evaluate the in vitro properties. Methods: The structures of all the synthesized copolymers were confirmed by 1 HNMR and Fourier transform infrared spectroscopy ( FTIR) . The drug-loaded micelles were prepared by a dialysis method. The micelles solution was freeze-dried and the lyoprotectants were screened. The critical micelle concentrations ( CMC) of the copolymers were measured by pyrene fluorescent probe technique. The distribution of particle size was measured by dynamic light scat-tering ( DLS) . The in vitro release behavior of the loaded micelles at different pH conditions was studied by a dialysis method. Re-sults:The CMC of micelles was 25. 63 mg·ml-1 . When 10% polyethylene glycol 4000 was used as the lyoprotectant, the re-solubili-ty of micelles was good and the distribution of particle size was narrow. The drug loading rate of micelles was 8. 12% and the encapsu-lation efficiency was 69. 33%. The average particle size of freeze-dried micelles was 183. 7 nm. The in vitro release of the drug-loaded micelles showed that the drug released slowly at pH 7. 4 and fast at pH 5. 0, which indicated that the change of pH could affect the drug release. Conclusion:The preparation of PEOz-PLA polymer micelles is simple. The particle size, entrapment efficiency and drug loading are controllable. The micelles have a certain sustained-release effect, which provides basis for further pharmacological study and clinical application.