Recent advance in role of cerebral microvascular lesions in type 2 diabetes mellitus-associated cognitive impairment / 中华神经医学杂志

Cognitive impairment is a common clinical complication in type 2 diabetes (T2DM). T2DM-related cognitive impairment has complex and multifactorial pathogenesis. Cerebral microvascular dysfunction is an important pathological change in patients with T2DM and pre-T2DM, and it can induce blood-brain barrier injury and impaired blood perfusion regulation, with disturbed neurovascular coupling and cerebral autoregulation, leading cognitive impairment. This article reviews the epidemiology and pathophysiological mechanisms related to T2DM cerebral microvascular lesions and cognitive impairment, and how to monitor changes of cerebral microvascular structure and function so as to provide new approach for diagnosis and treatment of T2DM-related cognitive impairment.

Recent advance in role and treatment of brain-derived neurotrophic factor imbalance in neurodegenerative diseases / 中华神经医学杂志

The two forms of brain-derived neurotrophic factor (BDNF), mature BDNF (mBDNF) and BDNF precursor (proBDNF), bind to corresponding receptors and mediate a series of biological signals, which play important roles in proliferation, survival and apoptosis. More and more studies have focused on the role of unbalanced transformation from proBDNF to mBDNF in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, as well as their potential as biomarkers and treatment targets. This article reviews the mechanism and therapeutic application of BDNF and proBDNF/mBDNF imbalance in the above-mentioned neurodegenerative diseases to provide new perspective and approach for the pathogenesis, early diagnosis and treatment of neurodegenerative diseases such as AD and PD.

Studies on orally disintegrating tablet of diphenhydramine hydrochloride and caffeine / 药学实践与服务

Objective To optimize the formulation and preparation of diphenhydramine hydrochloride and caffeine orally disintegrating tablet. Methods Melt granulation technology of steric acid and API was used to mask the unpleasant tasting of diphenhydramine hydrochloride. The tablets were prepared by direct pressing the dry powder with CCMC-Na as disintegrating agent. The formulation was optimized by orthogonal experiments to achieve the shortest disintegration time and the best taste correction. Results The optimized formula of orally disintegrating tablet was as follows： diphenhydramine hydrochloride 25 mg, caffeine 60 mg, stearic acid 25 mg, aspatan 40 mg, blueberry essence 7 mg, mannitol 45 mg, MCC 210 mg, CCMC-NA 25 mg, SDS 8 mg and magnesium stearate 5 mg. Conclusion This preparation method for orally disintegrating tablet of diphenhydramine hydrochloride and caffeine is practical and easy for quality control.

Analysis and prediction of thyroid cancer morbidity and mortality trends in China / 中华流行病学杂志

Objective: To analyze the morbidity and mortality trends of thyroid cancer in China from 1990 to 2019, explore the causes of the trends, and predict morbidity and mortality in the future. Methods: The morbidity and mortality data of thyroid cancer in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease database. The Joinpoint regression model was used to describe the change trends. Based on the morbidity and mortality data from 2012 to 2019, a grey model GM (1,1) was constructed to predict the trends in the next ten years. The model was tested by the posterior error method and residual test method. Results: In all populations, men and women, the AAPC values of the crude morbidity rates were 4.15% (95%CI: 3.86%-4.44%, P<0.001), 5.98% (95%CI: 5.65%-6.31%, P<0.001) and 3.23% (95%CI: 2.94%-3.53%, P<0.001) respectively, the AAPC values of age-standardized morbidity rates were 2.47% (95%CI: 2.12%-2.83%, P<0.001), 3.98% (95%CI: 3.68%-4.29%, P<0.001), 1.65% (95%CI: 1.38%-1.93%, P<0.001), the AAPC values of crude mortality rates were 2.09% (95%CI: 1.92%-2.25%, P<0.001), 3.68% (95%CI: 3.45%-3.90%, P<0.001), 0.60% (95%CI: 0.50%-0.71%, P<0.001). The age-standardized mortality rates in men showed a fluctuating trend of first decrease (1990-1994), then increase (1994-2012), and then decrease (2012-2019) (AAPC=1.35%, 95%CI: 1.16%-1.53%, P<0.001). The age-standardized mortality rate in women continuously decreased (AAPC=-1.70%, 95%CI: -1.82%- -1.58%, P<0.001). The GM (1,1) models can be used for medium and long-term predictions. The results of the residual test show that the average relative error values of all models are less than 10.00%, the prediction accuracy values are more than 80.00%, and the prediction effects are good. The results of the posterior error method show that all the prediction results are good except the qualified prediction of the age-standardized morbidity rate in men. In 2029, the crude morbidity rates would increase to 3.57/100 000, 2.78/100 000, and 4.40/100 000, respectively, and the age-standardized incidence rates would increase to 2.38/100 000, 1.89/100 000, and 2.88/100 000, respectively, the crude mortality rates would increase to 0.57/100 000, 0.62/100 000 and 0.53/100 000, and the age-standardized mortality rates would decrease to 0.33/100 000, 0.42/100 000 and 0.27/100 000 in all population, men and women in China. Conclusions: The overall, gender- specific age-standardized mortality rates showed downward trends in the last decade or so, and the prediction results showed that it might further decline. However, the crude morbidity rates, age-standardized and crude mortality rates have been on the rise, and the population aging is becoming increasingly serious in China, which requires close attention and targeted prevention and control measures.

C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.

Oblique lateral interbody fusion of 3D printed lateral fusion cage combined with percutaneous pedicle screw fixation for lumbar spondylolisthesis / 西安交通大学学报(医学版)

【Objective】 To discuss the early clinical effect of percutaneous pedicle screw fixation combined with oblique lateral interbody fusion（OLIF） of 3D printed lateral fusion cage for lumbar spondylolisthesis. 【Methods】 Total 21 patients with lumbar spondylolisthesis were enrolled in our study during September 2018 to August 2020. All the patients were treated with percutaneous pedicle screw fixation combined with OLIF of 3D printed lateral fusion cage. The time of operation， blood loss and complications were recorded. Clinical symptoms including low back pain and leg pain were evaluated using a visual analog scale （VAS）， the Oswestry disability index （ODI）， and the MOS item short from health survey （SF-36） before，1 week， and 6 months after surgery. CT and MRI images were evaluated before， 1 week， and 6 months after surgery. Disk height， interforaminal height， degree of upper vertebral slip and intervertebral fusion were evaluated with CT. Sagittal and axial diameters and cross-sectional areas of the spinal canal were evaluated with MRI. 【Results】 The average operation time of all the patients was （110.0±22.8） min， and the average intraoperative blood loss was （56.8±21.6） mL. All the patients were followed up 6 months after operation. The VAS score of lower back pain， VAS score of leg pain and ODI decreased from （6.8±1.6）， （5.6±1.8） and （57.6±13.4）% to （1.5±1.0）， （1.5±0.9） and （13.1±5.2）%， respectively. The differences were statistically significant （P<0.001）. The PCS and MCS scores of SF-36 increased statistically significantly from （27.3±11.8） and （52.4±14.6） before operation to （57.6±10.5） and （76.1±12.0） at follow-up， respectively （P<0.001）. Six months after operation， the height of intervertebral space， the height of intervertebral foramen， the percentage of slip， the sagittal diameter and axial diameter， and cross-sectional area of spinal canal were significantly different from those before operation （P<0.001）. Six months after operation， the fusion rate of the upper and lower interfaces of the 3D printed interbody fusion cage was 100%. There were no serious complications such as nerve or vascular injury after operation. 【Conclusion】 Posterior minimally invasive pedicle screw reduction and fixation technique combined with oblique lateral approach implantation of 3D printing lateral fusion cage in the treatment of lumbar spondylolisthesis has satisfactory early clinical results. This technique can provide a new choice for minimally invasive treatment of lumbar spondylolisthesis.

Comparison on the establishment of proprioceptive hypoesthesia model of anterior cruciate ligament by open surgery and minimally invasive surgery / 解剖学报

[Abstract] Objective To provide an optimized animal model for basic research by comparing the establishment of proprioceptive hypoesthesia model of anterior cruciate ligament (ACL) by open surgery and minimally invasive surgery. Methods Totally 30 normal cynomolgus monkeys were randomly divided into five groups: minimally invasive surgery group: unilateral ACL injury under arthroscope, n = 6; open surgery group: unilateral ACL injury through direct incision of knee joint, n = 6; minimally invasive sham operation group: unilateral ACL without injury through arthroscopic cleaning only, n = 6; open surgery group: unilateral ACL exploration without injury through direct incision of knee joint, n = 6; positive normal group: no surgical intervention, n = 6. Four weeks later, the neurophysiological examination [somatosensory evoked potentials (SEPs) and motor nerve conduction velocity (MCV)] was carried out. The macaque was killed and its unilateral ACL was stained with gold chloride. The number and variation of ACL proprioceptors were observed and recorded. Results In the aspect of neuroelectrophysiology, except the normal group, the latency of SEPs and MCV were prolonged, and the amplitude decreased. In terms of proprioceptors, the total number of minimally invasive surgery group: 578. 00± 12. 68, amplitude: 36. 33 ± 3. 72; total number of open surgery group: 367. 67 ± 9. 33, amplitude: 77. 00 ± 5. 55; total number of open sham operation group: 969. 00±18. 26, amplitude: 0±0; total number of normal group: 970. 46±16. 34, amplitude: 0± 0, the total number of proprioceptors decreased and the number of variation increased in all four groups except the normal group. At the same time, in the comparison of the two aspects, there were significant differences between the open operation group and the minimally invasive operation group, the open operation group and the open sham operation group, and the minimally invasive operation group and the minimally invasive sham operation group (P0. 05). Conclusion Both the open operation group and the minimally invasive operation group can build ACL proprioceptive hypoesthesia model, but the minimally invasive operation has less damage to the tissues around ACL, more scientific and single model, and less experimental error, which is of great significance in the basic research of ACL injury.

Whole-exome sequencing in diagnosing 2 cases of Gitelman syndrome / 中南大学学报(医学版)

Two patients with Gitelman syndrome were admitted to the Department of Endocrinology, Third Xiangya Hospital of Central South University. The genomic DNA from the patients' peripheral blood was extracted and the whole-exome sequencing was performed to detect the possible mutations. The function of the mutation sites was analyzed by bioinformatics software. Through whole-exome sequencing and Sanger sequencing, we have found that 2 patients with Gitelman syndrome carried compound heterozygous mutations of SLC12A3 gene, which were c.486_490delTACGGinsA, p.R943W, p.D486N, and p.R928C. Among them, c.486_490delTACGGinsA insertion deletion mutation causes frame shift and protein truncation. The p.R943W, p.D486N, and p.R928C of SLC12A3 gene were predicted to be pathogenic mutations by SIFT, PolyPhen2, and Mutation Taster. These 4 mutations were all reported, but p.R943W was first reported in Chinese population. Gitelman syndrome is rare in clinic and the rate of missed diagnosis is high. Early genetic analysis in patients with Gitelman syndrome is helpful to determine the etiology and guide the treatment.

Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Peripheral insulin resistance aggravated cognitive impairment and phosphorylated Tau protein in MAPT transgenic mice / 中华行为医学与脑科学杂志

Objective:To investigate the effects of insulin resistance induced by long-term high-fat diet on cognitive function and brain phosphorylated Tau protein in pR5 MAPT Tau transgenic mice.Methods:Eight-week-old female pR5 MAPT transgenic mice were divided into standard diet(STD) group (pR5 STD, n=8) and high-fat diet(HFD) group (pR5 HFD, n=8). Female wild-type C57BL/6 mice fed with STD were used as control group (WT STD, n=8). The experiment was carried out for 30 weeks until the mice were old.During the experiment, the weight of mice was measured once a week and fasting blood glucose was measured once every two weeks.Thirty weeks later, glucose tolerance test and insulin tolerance test were carried out.Forced swimming test and tail suspension test were used to evaluate the depressive behavior of mice, and elevated plus maze test was used to evaluate the anxiety behavior, Morris water maze test was used to evaluate spatial memory behavior.The levels of total Tau protein and phosphorylated Tau proteins H7-tau, p-tau-Ser396 and p-tau-Thr231 were detected by Western blot.SPSS 17.0 software was used for statistical analysis, repeated measurement ANOVA was used for the data of glucose tolerance test and insulin tolerance test, one-way ANOVA was used for multi group comparison, and LSD test was used for further pairwise comparison. Results:After 30 weeks of high-fat diet, there were significant differences in body weight and fasting blood glucose among the three groups ( F=808.31, 1 117.18, both P<0.01). The body weight of mice in pR5 HFD group ((54.35±2.52)g) was higher than those in pR5 STD group ((24.95±1.15) g) and WT STD group ((23.86±1.10) g) (both P<0.01), and the fasting blood glucose of mice in pR5 HFD group ((8.12±0.24) mmol/L) was significantly higher than those in pR5 STD group ((4.64±0.13) mmol/L) and WT STD group ((4.45±0.22) mmol/L) (both P<0.01). Glucose tolerance test showed that within 120 minutes after injection of glucose, there was a significant time and group interaction in the blood glucose value among the three groups ( F=113.30, P<0.01). After glucose injection, the peak value of blood glucose in pR5 HFD group was delayed, suggesting that glucose tolerance in pR5 HFD group was impaired.The insulin tolerance test showed that there was a significant interaction between time and group in the insulin tolerance among the three groups ( F=209.92, P<0.01). After injection of insulin, the blood glucose in pR5 HFD group decreased slowly, reaching the valley value at 60 min, and then the blood glucose increased significantly, suggesting that the sensitivity of pR5 HFD group mice to insulin decreased significantly.There were significant differences in the percentage of forced swimming immobility time and tail suspension immobility time among the three groups ( F=37.05, 59.29, both P<0.01). The two indexes of pR5 STD group and pR5 HFD group were both higher than those of WT STD group (all P<0.01), and those of pR5 HFD group were both higher than those of pR5 STD group (both P<0.01). The results of elevated plus maze showed that there were significant differences in the activity distance and time in open arm among the three groups ( F=7.82, 10.37, both P<0.05) .The activity distance ((0.40±0.21) m) and activity time ((27.38±8.80) s) of pR5 HFD group were significantly lower than those of pR5 STD group ((2.31±1.74) m, (63.56±27.52)s) (both P<0.05). The space exploration test showed that the residence time in the target quadrant of pR5 HFD group ((15.56±1.16)s) was less than that of pR5 STD group((19.18±0.64)s)( P<0.01), and the time of entering the platform area of pR5 HFD group((1.43±0.06)s) was less than that of pR5 STD group((1.66±0.12)s)( P<0.01). Western blot showed that there were significant differences in the levels of total Tau protein, H7-tau, p-tau-Ser396 and p-tau-Thr231 protein among the three groups ( F=101.50, 80.60, 55.47, 30.89, all P<0.05). Further pairwise comparison showed that the levels of the four Tau proteins showed: the levels of the proteins in pR5 STD group and pR5 HFD group were all higher than those of WT STD group (all P<0.01), and those in pR5 HFD group were all higher than those in pR5 STD group (all P<0.05). Conclusion:Long-term high fat diet causes obesity, hyperglycemia and peripheral insulin resistance, and promotes the cognitive impairment of MAPT mice, which is related to the increase of Tau protein phosphorylation in the brains of MAPT mice.

Using plant extracts and their active ingredients to inhibit bacterial biofilms / 生物工程学报

Numerous studies have reported that the resistance of biofilm bacteria to antibiotics can be up to 10-1 000 fold higher than that of planktonic bacteria. Bacterial biofilms are reported to be responsible for more than 80% of human microbial infection, posing great challenges to the healthcare sector. Many studies have reported that plant extracts and their active ingredients can inhibit the formation and development of bacterial biofilms, including reducing biofilm biomass and the number of viable bacteria in biofilms, as well as eradicating mature biofilms. This review summarized the plant extracts and their active ingredients that are inhibitory to bacterial biofilms, and analyzed the underpinning mechanisms. This review may serve as a reference for the development of plant drugs to prevent and treat biofilm infections.

Autonomic nervous symptoms as the initial presentation in systemic light-chain amyloidosis with multiple myeloma: a case report / 中华神经科杂志

Immunoglobulin light chain amyloidosis (AL) is characterized by the extracellular tissue deposition of insoluble fibrils as a result of protein misfolding. These tissue deposits may be responsible for progressive failure in several organs. Among them, neuropathy may be presented as the first manifestation. The patient reported here presented initially with autonomic nervous system impairment, mainly characterized by severe refractory orthostatic hypotension, which became progressively invalidating, forcing the patient to bed. Moreover, since the systemic involvement of the disease, the patient also presented with diarrhea, peripheral polyneuropathy, and kidney dysfunction. Eventually, the massive myocardial depression and infiltration led to a fatal outcome due to ventricular fibrillation. Examination revealed M protein in serum and urine protein electrophoresis. Rectal mucosa and skin biopsy confirmed amyloidosis, and bone marrow biopsy showed cellular infiltration was over 35% with 23% immature plasma cells. The patient was confirmed as AL with multiple myeloma.

Analysis of robot-assisted laparoscopic versus laparoscopic partial nephrectomy for the treatment of completely endophytic renal tumors / 中华泌尿外科杂志

Objective:To compare the efficacy and safety of robot-assisted laparoscopic and laparoscopic partial nephrectomy (RAPN and LPN) for patients with completely endophytic renal tumor.Methods:A total of 73 patients with completely endophytic renal tumor receiving RAPN (n=29) or LPN (n=44) in our center between January 2015 and June 2021 were retrospectively collected. There were 21 males and 8 females in RAPN group. The average age was 48.6±13.7 years old, average tumor size was 2.9±0.9 cm with 13 left tumors and 16 right tumors, average R. E.N.A.L. score was 9.2±1.0, and average preoperative eGFR was 82.6±10.7 ml/(min·1.73 m 2). There were 27 males and 17 females in LPN group. The average age was 50.1±12.3 years old, average tumor size was 2.9±0.9 cm with 24 left tumors and 20 right tumors, average R. E.N.A.L. score was 9.1±1.3, and average preoperative eGFR was 81.7±9.6 ml/(min·1.73 m 2). There was no significant difference in above variables between two groups. The operative time, warm ischemia time, blood loss, postoperative complication, postoperative hospital stay and postoperative 3 months renal function of two groups were compared. Results:All 73 patients successfully underwent RAPN or LPN and no patient converted to radical nephrectomy or open surgery. There was no significant difference in operation time [140(80, 160) min vs. 150 (90, 180) min, P=0.264], intraoperative estimated blood loss[150 (100, 200)vs. 180 (120, 200) ml, P=0.576]and postoperative hospital stay (7.0±2.7 vs. 7.4±2.1 days, P=0.480) between two groups. Compared with LPN group, RAPN group had obvious less warm ischemia time (23.1±3.3 vs. 27.6±4.7 min, P<0.001). No obvious complication occurred in RAPN group and one case with postoperative hemorrhage occurred in LPN group. No positive margin occurred in either group. There was no difference in renal function 3 months after operation between the two groups [73.2±6.3 vs.70.5±7.6ml/(min·1.73 m 2), P=0.117]. The median follow-up period was 22.6 months with no tumor recurrence or metastasis. Conclusions:For experienced surgeons, both RAPN and LPN are safe and feasible for patients with completely endophytic renal tumor. Compared with LPN, RAPN has advantages of perioperative curative effect, which could reduce the operating difficulty and shorten the warm ischemia time.

Comprehensive evaluation method of real-time non-reference ultrasound image involving soft tissue deformation / 生物医学工程学杂志

Ultrasound guided percutaneous interventional therapy has been widely used in clinic. Aiming at the problem of soft tissue deformation caused by probe contact force in robot-assisted ultrasound-guided therapy, a real-time non-reference ultrasound image evaluation method considering soft tissue deformation is proposed. On the basis of ultrasound image brightness and sharpness, a multi-dimensional ultrasound image evaluation index was designed, which incorporated the aggregation characteristics of the organization. In order to verify the effectiveness of the proposed method, ultrasound images of four different models were collected for experiments, including prostate phantom, phantom with cyst, pig liver tissue, and pig liver tissue with cyst. In addition, the correlation between subjective and objective evaluations was analyzed based on Spearman's rank correlation coefficient. Experimental results showed that the average evaluation time of a single image was 68.8 milliseconds. The evaluation time could satisfy real-time applications. The proposed method realizes the effective evaluation of real-time ultrasound image quality in robot-assisted therapy, and has good consistency with the evaluation of supervisors.

Application of pueumatic tourniquet in the operation of lower tibiofibular fracture / 中国骨伤

OBJECTIVE@#To investigate the complications of tourniquet in the clinical application of lower tibiofibular fracture.@*METHODS@#From June 2018 to September 2019, 33 cases of closed lower tibiofibular fractures (AO type 43A) were treated with plates and screws and were divided into two groups according to whether pueumatic tourniquet was used:16 cases in the observation group, 13 males and 3 females, aged 18 to 69 (38.8±17.0) years, the operation time after injury was (6.9±1.7) days, and tourniquet was not used during operation. There were 17 cases in the control group, 13 males and 4 females, aged from 21 to 71 (43.8±12.4) years, the operation time after injury was (6.5±1.0) days, automatic pneumatic tourniquetwas routinely used in the operation. The operation time, blood loss, postoperative swelling, pain and other complications were compared between two groups.@*RESULTS@#Total of 33 patients were followed up for an average of 15 months. There was no significant difference in operation time and blood loss between two groups (@*CONCLUSION@#The fracture of lower tibiofibular segment is superficial and easy to be exposed and fixed during operation. In order to avoid tourniquet complications, it is not recommended to use air bag tourniquet routinely or minimize the application time of tourniquet.

Selection of enteral nutrition regimens for children with abdominal Henoch-Schönlein purpura / 中国当代儿科杂志

OBJECTIVE@#To explore the reasonable and effective enteral nutrition regimen for children with abdominal Henoch-Schönlein purpura (HSP).@*METHODS@#A retrospective analysis was performed on the medical data of children with abdominal HSP who were hospitalized from August 2013 to August 2018. According to the starting time of enteral nutrition after abdominal pain relief, the children were divided into three groups: < 24 hours (@*RESULTS@#The retrospective analysis showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had a lower recurrence rate of clinical symptoms and the highest degree of satisfaction among their family members (@*CONCLUSIONS@#It is reasonable and effective to start the feeding with extensively hydrolyzed lactoprotein formula at 24-48 hours after abdominal pain relief in children with abdominal HSP.

Establishment of a cocrystal characterization method for sacubitril valsartan sodium / 药学学报

Sacubitril valsartan sodium (LCZ696) is an ionic cocrystal drug. The purpose of this study was to explore the cocrystal features of LC696 by establishing a variety of characterization methods, and thus provide basic research data for effective quality control. The cocrystal characteristics of LCZ696 and its tablets were identified by applying analytical means including powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), Raman spectra (RM), differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The crystalline water and hygroscopicity of LCZ696 were analyzed by thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), hygroscopicity test and Karl Fischer reaction method. The results show that PXRD, FTIR, DSC and ssNMR can effectively distinguish the features of LCZ696 cocrystal, sacubitril monomer, valsartan monomer, and sacubitril-valsartan (1∶1) mixture. RM can be used as a supplementary approach. Combined with the analysis by TGA, DVS, hygroscopicity test and Karl Fischer reaction method results, LCZ696 contains 2.5 crystalline water molecules and is very hygroscopic; we recommend that LCZ696 be stored in an environment with a relative humidity below 60%. By characterizing the crystal features we can establish quality control measure and evaluate the stability of the drug tablets. This study provides data in support for the establishment of the LCZ696 quality standard.

Trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai from 1993 to 2017 / 上海预防医学

Objective:To characterize the trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai， thus optimizing the prophylactic options for this malignancy. Methods:Data from Shanghai Cancer Registration and Reporting System were used to analyze the colorectal cancer prevalence in Jing'an District from 1993 to 2017. Joinpoint software was used to analyze the trends in the standardized incidence rate and mortality rate by calculating the annual percentage of change （APC） and the average annual percentage of change （AAPC）. Results:A total of 13 580 new cases of colorectal cancer were reported in Jing'an District during 1993 and 2017， with an average crude incidence rate of 52.94/105 and a standardized incidence rate of 24.77/105. The total number of deaths was 7 572， with an average crude mortality rate of 29.52/105 and a standardized mortality rate of 12.20/105. The standardized incidence rate of colorectal cancer in Jing'an District from 1993 to 2017 showed an increasing trend （AAPC=1.64%，P<0.001）， and the standardized incidence rate of colorectal cancer in both sexes increased （AAPC： 2.10% in men， 1.04% in women）. The age-standardized mortality rate （ASMR） did not change significantly. The incidence rate of colorectal cancer increased in men in both age groups of 50 to 74 years and 75 years and older， with an AAPC of 2.07% and 3.32%， respectively. However， this was not evident in women of all age groups. The mortality rate of colorectal cancer in men aged 0-49 years， as well as in men and women at 50-74 age groups， decreased significantly， with an AAPC of -7.46%，-1.13%， and -2.72%， respectively. The mortality rate of colorectal cancer in men of 75 years or older showed no significant trend， while that in women of 75 years or older increased （AAPC=2.30%）. Conclusion:The overall standardized incidence rate of colorectal cancer in Jing'an District from 1993 to 2017 was increased， and ASMR did not change significantly. Public health prophylactic options are suggested， including improvement of lifestyle/physical activity and eradication of precancerous lesion polypus in males aged ≥50 years to reduce the incidence of colorectal cancer， and enforcement of second-grade prophylaxis in females aged ≥75 years to decrease the mortality of colorectal cancer.

An empirical study on the evaluation of the educational quality of clinical practice bases for master of nursing specialist / 中国实用护理杂志

Objective:To compile the evaluation scale of the quality of education in the clinical practice base of full-time Master of Specialist Nursing (MNS) based on student participation and the SERVQUAL model, evaluate the quality of clinical practice base, and provide reference for the evaluation of clinical practice base.Methods:Based on the theory of student participation and the SERVQUAL model, the evaluation scale of the educational quality of clinical practice base of MNS was constructed. By facilitating sampling methods, 176 MNS students from 11 universities in 6 provinces were selected, and a questionnaire of self-compiled general information and a survey of the evaluation scale of education quality of MNS clinical practice base were distributed.Results:The evaluation scale of education quality of clinical practice base of MNS contained 28 entries in five dimensions: tangibility, reliability, responsiveness, guarantee and empathy. The total Cronbach alpha coefficient of the scale was from 0.983 to 0.987, item level content validity index was from 0.92 to 0.96, scale level content validity index was 1 and the correlated coefficient of the structural validity Pearson was from 0.785 to 0.966. To explore factor analysis, the dimension value of the scale KMO value was greater than 0.7, and the expected part and the actual feel part KMO value were 0.956 and 0.963 respectively. The number of common factors was 2 and 3 respectively, and the cumulative interpretation variation was 79.1% and 78.4% respectively.The actual perception of the quality of education in the clinical practice base of MNS was lower than expected, and the differences in entries were statistically significant ( P<0.05). The analysis of multiple linear regression showed that the teaching time and level of clinical practice base undertaken by clinical practice base were the main factors affecting the expectation and actual feeling value ( P<0.05). The importance performance analysis analysis found that 11 entries were in the advantage zone, 3 entries were in the maintenance area, 12 entries were in the minor improvement area and 2 entries were in the priority improvement area. Conclusions:The evaluation scale of the quality of education of the clinical practice base of MNS have good confidence and validity. The actual degree of educational quality of the clinical practice base of MNS is lower than expected. The teaching time and level of clinical practice base undertaken by clinical practice base are the main factors that affect expectation and actual feeling. It is urgent to improve the theoretical knowledge and practice level of tutors and deal with occupational exposure experienced by MNS students.

Rule mining of acupoint and medication selection of acupoint application therapy for functional constipation / 中国针灸

OBJECTIVE@#To analyze the rules of acupoint and medication selection of acupoint application therapy for functional constipation (FC) by data mining technology.@*METHODS@#The clinical research literature regarding acupoint application therapy for FC from published to February 26, 2020 was searched in CNKI, VIP, Wanfang, SinoMed and PubMed. The prescriptions were extracted, and by using SPSS24.0 and SPSS Modeler14.0 software, the use of high-frequency acupoints and medication was summarized. The association rule analysis, cluster analysis and core prescription analysis of acupoints and medication were analyzed.@*RESULTS@#A total of 122 prescriptions of acupoint application therapy were included, involving 32 acupoints. The core prescription of acupoints was Tianshu (ST 25), Dachangshu (BL 25), Shenque (CV 8) and Guanyuan (CV 4). The high-frequency meridians mainly included conception vessel, @*CONCLUSION@#The use of local acupoint and regulating-