Research progress in micro/nanobubbles for ultrasound diagnosis or treatment / 药学学报

In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

Comparison of clinical efficacy and stability of Toric implantable collamer lens implantation in different orientations / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the clinical efficacy, vault, and rotational stability of horizontal, oblique, and vertical implantation of Toric implantable collamer lens(TICL).METHODS: Retrospective cohort study. A total of 92 cases(120 eyes)who underwent TICL implantation from July 2018 to March 2022 and had regular follow-up for at least 1 a postoperatively(1 d, 1 wk, 1, 3, 6 mo, and 1 a)at Wuhan Bright Eye Hospital were collected. The patients were divided into three groups, with 34 cases(45 eyes)in horizontal implantation group, 25 cases(29 eyes)in oblique implantation group(29 cases), and 33 cases(46 eyes)in vertical implantation group. Uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA), diopters, vault, and rotation angle(deviation of the actual axis of TICL from the expected axis).RESULTS: All surgeries were uneventful, and there were no complications such as infection, secondary glaucoma, or cataract opacity. Safety and efficacy of the surgery: the CDVA of the three groups of patients was better than or equal to the preoperative CDVA at 1 a postoperatively, and there was no statistically significant differences in postoperative UDVA and CDVA of the three groups(P>0.05). The safety index at 1a postoperatively was 1.34±0.21, 1.34±0.17, and 1.31±0.18 for the horizontal, oblique, and vertical groups, respectively. The efficacy index was 1.26±0.21, 1.33±0.18, and 1.27±0.16 for the three groups, respectively, both with no statistically significant differences(P>0.05). Vault: there was a significant difference in postoperative vault among the three groups(P=0.003), with the vertical group having the lowest vault, followed by the horizontal group and the oblique group. The vaults at different follow-up time points within each group showed significant differences(P<0.001), and all decreased over time. Residual astigmatism: there was no significant difference in residual astigmatism among the three groups(P=0.130), but there were differences at different follow-up time points within each group(P<0.001). Rotation angle: no significant differences in rotation angle were observed among the three groups(P=0.135), but there were differences at different follow-up time points within each group(P<0.001).CONCLUSION: The implantation of TICL in different orientations has good safety and efficacy, the postoperative rotational stability is good, and the appropriate angle can be selected to implant TICL according to the clinical situation.

Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Programmed Intermittent Epidural Bolus in Comparison with Continuous Epidural Infusion for the Effects of Enhanced Recovery after Cesarean Section / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of programmed intermittent epidural bolus （PIEB） and continuous epidural infusion （CEI） on enhanced recovery after cesarean section. MethodsTotally 120 women scheduled to undergo elective cesarean section under combined spinal and epidural anesthesia， aged 18-45 years， with single fetus， full-term pregnancy （≥37 weeks）， ASA grade II or III， were recruited， with 60 cases in each group. At the end of the surgery， after a similar epidural loading dose， patients were randomLy assigned to receive either PIEB （6 mL·h-1 beginning 30 minutes after the loading dose） or CEI （6 mL·h-1， beginning immediately after the loading dose） for the maintenance of analgesia with 0.1% ropivacaine. At 2， 6， 12， 24 and 36 h postoperatively， VAS score was used to evaluate the composite pain， and Bromage Score was used to evaluate the degree of lower extremity motor block. The time to first flatus， time to first ambulation and the satisfaction scores were also recorded. ResultsThe VAS scores at 12， 24 and 36 h postoperatively and the lower extremity motor block scores at 6， 12 and 24 h postoperatively in the PIEB group were significantly lower than those in the CEI group （P < 0.01）. The epidural analgesic dosage was less in the PIEB group than that of the CEI group （P=0.002）. The time to first flatus and time to first ambulation were significantly shorter than those in the CEI group （P < 0.05）. The satisfaction scores were significantly higher in the PIEB group than in the CEI group （P < 0.05）. There was no significant difference in the first urination time after urinary catheter removal and the length of hospital stay between the two groups （P > 0.05）. ConclusionCompared with CEI， PIEB provides better postoperative analgesia， less motor block scores， lower epidural analgesic dosage， shorter the time to first flatus and defecation and time to first ambulation， and greater patient satisfaction， which is more consistent with the ERAS concept of analgesia.

Overlap esophagojejunostomy with multi-mode modifications in totally laparoscopic total gastrectomy: safety and feasibility of 152 cases from a single center / 中华胃肠外科杂志

Objective: Currently, the Overlap anastomosis is one of the most favored reconstruction methods of intracorporeal esophagojejunostomy (EJS). Despite many advantages of the method, it remains some shortcomings to be improved when it comes to the retraction of the esophagus stump, the insertion of the anvil fork of the linear stapler into a "pseudo" lumen, and the closure of the common entry hole. This study aims to investigate the safety and feasibility of a multi-mode modified Overlap anastomosis. Methods: A descriptive case series study was conducted. Medical records of 152 consecutive patients who underwent totally laparoscopic total gastrectomy (TLTG) with our multi-mode modified Overlap EJS method by the same surgical team at our department from February 2017 to June 2020 were retrospectively analyzed. The multi-mode modified Overlap method mainly included (1) After ensuring the safety of tumor resection margin (proximal margin was at least 3 cm from the tumor), the esophagus was partially transected from left to right (with 5-8 mm width esophagus continuation). The specimen was then placed in a plastic bag which was tied up at the mouth using strings with a part of the esophageal wall poking through. Then the plastic bag containing the specimen was transferred to the right lumbar region, while the patient's body position was adjusted so that the abdominal esophagus could be pulled by the gravity of the specimen. (2) Using the "three-direction traction" method. The esophageal lumen was properly exposed, then guided by the gastric tube, the anvil fork was accurately placed into the esophageal lumen for completing the side-to-side EJS. (3) The 3-0 barbed suture was used in the closure of the common entry hole of the stapler from dorsally to ventrally with simple one-layer continuous suture (the stitch going from inside to inside) followed by continuous Lembert's suture (the stitch going from outside to outside). Combined with clinicopathological characteristics, the perioperative outcomes and postoperative complications of the whole group were analyzed and evaluated. Results: The study cohort included 129 men and 23 women, with a mean age of (60.2±9.1) years and a mean body mass index (BMI) of (23.2±3.1) kg/m(2). Of the 152 patients, 23 patients (15.1%) had a history of previous abdominal surgery; dentate line was invaded by tumor in 21 patients (13.8%). The mean length of the proximal resection margin was (3.3±0.3) cm and the postoperative pathological examination indicated negative resection margin tumor. The mean operative time and anastomotic time were (302.1±39.9) minutes and (29.8±5.4) minutes, respectively. The mean estimated blood loss was (87.9±46.4) ml. The mean length of postoperative hospital stay was (12.3±7.3) days. The overall severe postoperative complications (Clavien-Dindo ≥ II) occurred in 22 patients (14.5%). Six cases of pancreatic leakage were successfully recovered by adequate drainage, inhibition of pancreatic exocrine secretion and nutritional support. Ten cases of pneumonia and three cases of abdominal infection were cured with anti-infection and physical therapy. Two patients developed anastomotic leakage postoperatively. One case was caused by excessive tension of the Roux loop of the jejunum and excessive opening on the side of the jejunum after side-to-side anastomosis, and the other case was caused by an accidental intraoperative occurrence of "nasogastric tube stapled to the side-to-side anastomosis". Both of them recovered after conservative treatment including adequate drainage, anti-infection, and adequate nutritional support. One patient underwent immediate open surgery because of Peterson's hernia 7 days after TLTG, and the patient died due to extensive small bowel necrosis. Conclusions: Multi-mode modified overlap method simplifies the operation and reduces the difficulty of EJS. It is a safe and feasible method for EJS.

Clarification on Kidney-deficiency Constipation Treated by Classic Prescription Jichuanjian / 中国实验方剂学杂志

Jichuanjian， from the Jing Yue’s Collected Works by Zhang Jingyue， a famous doctor of Ming Dynasty， is composed of Angelica， Achyranthes bidentata， Cistanche deserticola， Alismatis Rhizoma， Shengma and Fructus Aurantii. It is one of the first 100 classic prescriptions published by the National Administration of Traditional Chinese Medicine. The original book states that where the disease is related to deficiency， with impacted stool， medicines such as Xiaohuang prescription cannot be used. If the treatment is needed， Jichuanjian should be applied. Through the textual research of ancient and modern literature， it is found that the efficacy of Jichuanjian has changed from ancient to modern times. In the medical books of the Ming and Qing Dynasties and the modern ones， the treatment is mostly carried out based on the constipation due to deficiency recorded in the original book， while in contemporary times， the treatment of Jichuanjian focuses on kidney （yang）-deficiency constipation and yin-deficiency constipation. Especially since modern times， Jichuanjian is frequently used to treat kidney-deficiency constipation according to the description in the planning textbooks of traditional Chinese medicine colleges and universities， which causes doubts among the authors. To actively respond to the call of General Secretary Xi Jinping that we should strengthen the sorting and excavation of the essence of classical medical books， this paper analyzed and demonstrated the original text and the drug composition， traceability and application by future generations of Jichuanjian based on the Jing Yue’s Collected Works. It was concluded that Jichuanjian was prepared for the treatment of constipation due to weak constitution， fluid deficiency， and emergent purgation， aiming for constipation due to weak constitution and fluid consumption rather than kidney-deficiency constipation described in modern textbooks. As Jichuanjian was developed for similar syndromes， it was reasonable that it was understood by later generations of doctors from the perspective of liver and kidney as well as earth dampness and wood stagnation， which however remains to be further explored and verified in clinic. By combing and discussing the efficacy of Jichuanjian， this paper could provide theoretical basis for the clinical application and modern development of Jichuanjian.

Associations between 24-hour urinary sodium excretion and all-cause mortality in adults living in north China / 中华心血管病杂志

Objective: To investigate the associations between 24-hour urinary sodium excretion (24hUNaE) and all-cause mortality in adult Northern Chinese population. Methods: Data from this study were derived from the prospective urban and rural epidemiology (PURE) study in north China. Baseline information of all participants were obtained by face to face interview through trained research staffs based on questionnaires, and morning fasting urine samples of participants were collected to estimate 24hUNaE and 24-hour potassium excretion (24hUKE). Multivariable frailty Cox regression models were used to explore the association between 24hUNaE (<3.00, 3.00-3.99, 4.00-4.99, 5.00-5.99 and ≥6 g/d) and all-cause death. Results: A total of 27 310 participants were included in this study. The mean 24hUNaE was (5.84±1.73) g/d. After a median follow-up of 8.8 years, 1 024 participants died (3.7%), including 390 cardiovascular related deaths and 591 non-cardiovascular related deaths. The cause of death of the remaining patients could not be determined. Using 24hUNaE level of 4.00-4.99 g/d as the reference group, after fully adjustment, 24hUNaE ≥6.00 g/d was associated with an increased risk of all-cause death (HR=1.24, 95%CI: 1.02-1.49) and cardiovascular related death (HR=1.39, 95%CI: 1.02-1.88). 24hUNaE<3.00 g/d was associated with increased risk of all-cause mortality (HR=1.38, 95%CI: 0.96-1.99). There was no significant association between 24hUNaE and non-cardiovascular related death. Furthermore, using the combination of 24hUNaE 4.00-4.99 g/d and 24hUKE≥2.11 g/d as the reference group, the highest risk occurred in participants with the combination of low sodium (<3.00 g/d) and low potassium (<2.11 g/d). Conclusion: 24hUNaE equal or higher than 6 g/d or lower than 3 g/d is associated with increased risk of all-cause mortality and cardiovascular related death in Northern Chinese population. Besides, moderate sodium intake in combination with increased potassium intake might reduce the risk of all-cause death.

Thermostable CRISPR/Cas9 genome editing system and its application in construction of cell factories with thermophilic bacteria: a review / 生物工程学报

The diverse thermophilic strains of Thermoanaerobacter, serving as unique platforms with a broad range of application in biofuels and chemicals, have received wide attention from scholars and practitioners. Although biochemical experiments and genome sequences have been reported for a variety of Thermoanaerobacter strains, an efficient genetic manipulation system remains to be established for revealing the biosynthetic pathways of Thermoanaerobacter. In line with this demand, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) systems for editing, regulating and targeting genomes have been well developed in thermophiles. Here, we reviewed and discussed the current status, associated challenges, and future perspectives of the construction of thermostable CRISPR/Cas9 genome editing systems for some representative Thermoanaerobacter species. The establishment, optimization, and application of thermostable CRISPR/Cas genome editing systems would potentially provide a foundation for further genetic modification of thermophilic bacteria.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis / 中华医学杂志(英文版)

BACKGROUND@#Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.@*METHODS@#From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.@*RESULTS@#Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.@*CONCLUSIONS@#LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Retrospective analysis clinical characteristics of female stress urinary incontinence and efficacy of transobturator tension-free vaginal tape procedure / 中华泌尿外科杂志

Objective:To explore the clinical characteristics of patients with female stress urinary incontinence(SUI) and efficacy of Transobturator Tension-free vaginal tape procedure.Methods:We retrospectively analyzed the clinical data of 319 cases who were operated transobturator tension free vaginal tape in Shanghai Changhai Hospital Affiliated of Naval Medical University from Oct.2009 to Jun.2018. Patients age ranged from 39 to 91 years old, with the average age of(59.2±9.7)years old. 145(45.5%) patients aged ≥60 years old. Among them, 155 (48.6%) patients with moderate SUI, 164(51.4%) with severe SUI.96 cases(30.1%) hypertension, 24(7.5%)diabetes, 2(0.6%)had not given birth, 317(99.4%)patients had given birth more than once. 31(9.7%) coexisting pelvic organ prolapse with POP-Q stage 2 and above. Maximum urinary flow rate ranged 5.2-72.6 ml/s. Cystometric capacity ranged 56.7-1 013.6 ml. Average preoperative ICIQ-SF score was 13.9 (range 9-19).Results:Operative time of 288 TVT-O procedures ranged 19-60 min, and 31 cases in the surgical management of cystocele with concomitant ranged 50-120 min. A total of 265 patients were evaluable followed up for 12-24 months, Objective cure rate and subjective cure rate were achieved in 95.8%(254 cases) and 93.6%(248 cases) respectively. POP was cured in 96.8% patients.Postoperative complications were 10.6% groin pain, 4.5% urgency, others including urinary tract infection(3.4%), de novo dysuresia(2.6%), dyspareunia(1.1%), and one case of bladder injury, one case sling erosion and one case scar hyperplasia.Conclusions:Female stress urinary incontinence were mainly in middle-aged and elderly people who had severely psychological quality of life lasting for several years. TVT-O may achieve a high success or improvement rate and no serious adverse effects. One operation could correct the stress urinary incontinence and simultaneously correct prolapse.

Taste-Masking Effect of Montelukast Sodium Orally Disintegrating Tablets Using Electronic Tongue Analysis and Human Sensory Evaluation Method / 中国药学杂志

OBJECTIVE: To investigate the taste-masking effect of montelukast sodium orally disintegrating tablets using electronic tongue technology and human sensory evaluation and determine the optimum formulation. METHODS: Orally disintegrating tablets were prepared with five different concentrations of flavoring agents or without flavoring agent.The tastes of those tablets were determined by electronic tongue, and principal component analysis and linear discriminant analysis were used to evaluate differences of different formulations. The taste-masking effect of the tablets was investigated combined with electronic tongue analysis and sensory evaluation of subjects. RESULTS: The taste of orally disintegrating tablet was the best when the total amount of flavoring agent was 1.6 mg, and the ratio of sweetening agent to aromatic agent was 5∶3. CONCLUSION: The combination of electronic tongue and human sensory assess can evaluate the taste-masking effect of orally disintegrating tablets and provide the basis for determining the optimum formulation.

Lung transplantation in China between 2015 and 2018 / 中华医学杂志(英文版)

BACKGROUND@#Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China.@*METHODS@#We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort.@*CONCLUSIONS@#Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice / 中华医学杂志(英文版)

<p><b>Background</b>Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.</p><p><b>Methods</b>We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.</p><p><b>Results</b>We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.</p><p><b>Conclusion</b>The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.</p>

Role of STAT1 signaling pathway in osteoblast apoptosis and effect of blocking the path / 中国医师杂志

Objective To investigate the role of signal transducer and activator of transcription (STAT1) signaling pathway in osteoblast apoptosis,and to study the effect of STAT1 inhibitor (fludarabine) on osteoblast.Methods The viability of the osteoblasts in different concentration of fludarabine was detected by cell counting kit-8 (CCK-8) assay.Osteoblasts were divided into 4 groups:control group,dexamethasone (Dex) group,fludarabine (Flu) group,and Dex + Flu group.Enzyme linked immunosorbent (ELISA) was used for determining the protein expression of Bcl-2 Associated X Protein (BAX),STAT1 and phosphorylation-sigual transducers and activators of transcription 1 (p-STAT1),and cleaved caspase-3 to reflect the apoptosis in all groups.Results Treatment with Dex increased the protein expression of apoptosis-related proteins and p-STAT1 in time-dependent and dose-dependent manner.Exposure of the cells to Flu,which was a selective STAT1 inhibitor,resulted in a decreased the protein levels of apoptosis-related proteins.Conclusions Our results suggest that fludarabine could suppress Dex-induced apoptosis through the inhibition of STATl-mediated up-regulation cleaved caspase-3 expression in osteoblasts.

Characteristic analysis of insulin secretion and sensitivity in pre-diabetes populations under new diagnostic criteria / 上海交通大学学报（医学版）

Objective: To investigate the characteristics of insulin secretion function and sensitivity and blood glucose disposition capacity in the prediabetes populations. Methods: A total of 1 317 subjects were enrolled in this study, including 382 with normal glucose tolerance (NGT) and 935 with pre-diabetes. All pre-diabetes populations were divided into seven subgroups according to the cut-off points of 2010 American Diabetes Association standards. Homeostasis model assessment (HOMA) was used to access baseline insulin secretion (HOMA-β) and insulin sensitivity (HOMA-IR). Insulin secretion and sensitivity after glucose load were evaluated by area under curve (AUC) for insulin/AUC for glucose (AUCINS120/AUCGLU120) and insulin sensitivity index (ISI) calculated from Cederholm formula, respectively. Disposition index (DI) was used to reflect blood glucose disposition capacity. Results: The most common type of pre-diabetes was impaired fasting glucose (IFG) combined with impaired glucose tolerance (IGT) and glycated hemoglobin A1c (HbA1c ) 5.7%-6.4%, followed by isolated IGT, while the proportion of isolated IFG was the lowest. The insulin sensitivity of isolated HbA1c 5.7%-6.4% group was better than that of isolated IFG group, isolated IGT group, and IFG combined with IGT group (P<0.05). And its β-cell function was similar with the other subgroups. The DI value of isolated HbA1c 5.7%-6.4% group was about 1.5 times of that of isolated IGT group and IFG combined with IGT group (P=0.000), which was similar with isolated IFG group. The function of β cell or insulin sensitivity in the pre-diabetes subjects with HbA1c 5.7%-6.4% was further damaged compared with the pre-diabetes people whose HbA1c were lower than 5.7%. Conclusion: Different types of pre-diabetes are significantly heterogeneous under new diagnostic criteria, and further prospective studies with a larger sample size are needed to clarify whether HbA1c 5.7%-6.4% is suitable as a diagnostic criteria for pre-diabetes in Chinese population.

Preparation of Montelukast Sodium Orally Disintegrating Tablets and Study on the Bioequivalence in Beagle Dogs / 中国药学杂志

OBJECTIVE: To prepare montelukast sodium orally disintegrating tablets and investigate the bioequivalence in Beagle dogs. METHODS: The orally disintegrating tablets were prepared by direct compression method,and the optimal formulation was screened by orthogonal test.HPLC-fluorescence method was developed for determination of montelukast sodium plasma concentration in Beagle dogs. RESULTS: The optimized formulation(1 000 tablets) was montelukast sodium 10.4 g, microcrystalline cellulose 60 g, cross linked povidone 30 g, mannitol 15 g, magnesium stearate 2 g, aerosil 1 g, aspartame 1 g, flavor 0.6 g. CONCLUSION: Montelukast sodium orally disintegrating tablets made of the optimized formulation could disintegrate rapidly. Relatively bioavailability of montelukast sodium orally disintegrating tablets is 90.7%.

Risk Factors for Recurrence of Ovarian Endometriosis in Chinese Patients Aged 45 and Over / 中华医学杂志(英文版)

<p><b>Background</b>When considering the issue of recurrence, perimenopausal women may have more dilemma during management comparing with young women, for example, whether to retain the uterus and ovary during surgery, whether it is necessary to add adjuvant medicine treatment after operation, and there is no evidence for reference about using of gonadotropin-releasing hormone agonist. This study aimed to study the risk factors for the recurrence of ovarian endometriosis (EM) in patients aged 45 and over.</p><p><b>Methods</b>This is a retrospective nested case-control study. We reviewed the medical records of patients aged over 45 years who underwent surgical treatments for ovarian EM from 1994 to 2014, in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences. By following up to January 2016, 45 patients were found to have relapses and regarded as the recurrence group. The patients with no recurrence during the same follow-up period were randomly selected by the ratio of 1:4 as the nonrecurrence group (180 patients in total). Stratified Cox regression was used to analyze the risk factors of the recurrence.</p><p><b>Results</b>Univariate analysis showed that there was a significant difference in the postoperative treatment (the percentage of patients who received postoperative treatment in non-recurrence group and recurrence group, 23.9% vs. 40.0%, χ = 4.729, P = 0.030) and ovarian preservation (the percentage of patients who received surgery of ovarian preservation in non-recurrence group and recurrence group, 25.0 % vs. 44.4%, χ = 19.462, P < 0.001) between the nonrecurrence group and the recurrence group. There was no correlation between recurrence and the following factors including patient's age, menarche age, gravidity, parity, CA125 level, ovarian lesions, menopausal status, combined benign gynecological conditions (such as myoma and adenomyoma) and endometrial abnormalities, and surgical approach or surgical staging (all P > 0.05). Multivariate analysis indicated that whether to retain the ovary was the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM (odds ratio: 5.594, 95% confidence interval: 1.919-16.310, P = 0.002).</p><p><b>Conclusion</b>Ovarian preservation might be the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM.</p>

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure.</p><p><b>METHODS</b>Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice.</p><p><b>RESULTS</b>Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain.</p><p><b>CONCLUSIONS</b>This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.</p>

Modified Snodgrass technique for hypospadias / 中华男科学杂志

Objective@#To investigate the clinical effect of modified Snodgrass surgical technique in the treatment of hypospadias.@*METHODS@#We retrospectively analyzed the clinical data about 212 cases of hypospadias treated by urethroplasty from January 2008 to October 2016, 94 with the modified Snodgrass technique, namely with a silk line in addition to the urethral suture to make easier postoperative removal of the suture (group A), and the other 118 with the conventional Snodgrass technique (group B). The urethral suture was removed at 10 days after surgery for the patients in group A. We compared the success rate of surgery and incidence of postoperative complications between the two groups.@*RESULTS@#Compared with group B, group A showed a significantly higher success rate of surgery (81.36% vs 91.49%, P 0.05).@*CONCLUSIONS@#The modified Snodgrass technique can improve the success rate of surgery and reduce the incidence rates of incisional infection and urinary fistula, which deserves wide clinical application.