Objective To explore the significance of proton magnetic resonance spectroscopy(1H- MRS)in patients with amyotrophic lateral sclerosis(ALS).Methods Single-voxel1 H-MRS was carried on the preeentral gyri in 110 patients with ALS and 24 patients with lower motor neuron syndrome (LMNS) compared with 89 healthy controls.The upper motor neuron involvement of the patients was assessed by upper motor neuron(UMN)signs and the reflex scale,and the disease severity was evaluated by the AIJS function rating scale(ALS-FRS)and APPEL ALS rate scale(AARS).Results Compared with the healthy controls(1.62±0.18),the NAA/Cr of patients with ALS(1.40±0.25)remarkably decreased (t= -5.007,P=0.000),however,it did not change in patients with LMNS(1.60±0.17)as compared with that of the controls.The NAA/Cr of patients with ALS was also lower than that of patients with LMNS(t= -2.660,P=0.009).Furthermore,the NAA/Cr of patients with definite ALS was lower than those of patients with probable and possible ALS(definite vs probable:t=-2.626,P=0.010;definite vs possible: t=-2.537,P=0.013).On the other hand,patients with pronounced UMN signs had a lower NAA/Cr ratio than those with probable UMN signs(t=-2.827,P=0.006).In patients with asymmetric clinical presentation,the NAA/Cr ratio was significantly lower in the precentral gyrus contralateral to the clinically predominantly affected side(t=-2.652,P=0.011).The NAA/Cr was correlated with the reflex scale scores,ALS-FRS score,and AARS and its sub-items(P＜0.05). Conclusions 1H-MRS is useful in studying ALS.The marker NAA/Cr of precentral gyrus may reflect the UMN degeneration in ALS,which is related to the disease severity and progression.However,it might not be helpful in the early diagnosis and differential diagnosis of the disease.

Objective To investigate the effects of the extent of regional lymph node dissection on the prognosis of patients with T4 gallbladder carcinoma.Methods The retrospective cohort study was conducted.The clinicopathological data of 64 patients with T4 gallbladder carcinoma who underwent radical cholecystectomy in the 4 medical centers between January 2013 and December 2016 were collected,including 31 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,16 in the First Affiliated Hospital of Xi'an Jiaotong University,11 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 6 in the Affiliated Hospital of North Sichuan Medical College.There were 27 males and 37 females,aged from 35 to 77 years,with a median age of 59 years.Sixty-four patients underwent radical cholecystectomy and regional lymph node dissection.According to the extent of intraoperative lymph node dissection,25 patients (13 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,6 in the First Affiliated Hospital of Xi'an Jiaotong University,4 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 2 in the Affiliated Hospital of North Sichuan Medical College) whose extent of lymph node dissection involved lymph nodes next to cystic duct,hepatoduodenal ligament,back of head of pancreas,next to common hepatic artery and celiac trunk were allocated into the extended dissection group,39 patients (18 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,10 in the First Affiliated Hospital of Xi'an Jiaotong University,7 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 4 in the Affiliated Hospital of North Sichuan Medical College) whose extent of lymph node dissection involved lymph nodes next to cystic duct and hepatoduodenal ligament were allocated into the control group.Observation indicators:(1) postoperative complications;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival up to January 2018.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated with the independentsample t test.Count data were represented as absolute number or percentage,and comparison between groups was analyzed using the chi-square test and Fisher exact probability.The survival curve was drawn using the KaplanMeier method,and the comparison of survival rates was done by the Log-rank test.Results (1) Postoperative complications:64 patients with T4 gallbladder carcinoma underwent successful radical cholecystectomy and regional lymph node dissection,without intraoperative death.Twelve patients had different degrees of postoperative complications.Four of 7 patients undergoing extended radical cholecystectomy had postoperative complications.Twenty-five patients in the extended dissection group were cured by conservative treatment,including 4 with intraperitoneal infection and 2 with pancreatic leakage,with a complication incidence of 24.0％ (6/25).Thirtynine patients in the control group were cured by conservative treatment,including 5 with intraperitoneal infection and 1 with gastric retention,with a complication incidence of 15.4％ (6/39).There was no statistically significant difference in the complication incidence between the two groups (x2=0.284,P＞0.05).(2) Follow-up and survival situations:64 patients were followed up for 1-60 months.The postoperative overall median survival time was l l months.The postoperative median survival time,1-,3-and 5-year cumulative survival rates were respectively 18 months,80％,16％,9％ in the extended dissection group and 8 months,21％,4％,0 in the control group,with a statistically significant difference in the prognosis between the two groups (x2=14.744,P＜ 0.05).Conclusions On the premise of practiced surgical skill,extended regional lymph node dissection cannot increase incidence of surgical complication in patients with T4 gallbladder carcinoma after radical resection.Actively extending lymph node dissection up to near common hepatic artery,peri-celiac trunk and back of head of pancreas can improve long-term survival and prognosis.

OBJECTIVEThe term "premature thelarche" refers to isolated breast development before 8 years of age in female, without any other signs of sexual maturation, while "gynecomastia" is the presence of breast tissue in males. This study aimed to investigate the prevalence of premature thelarche and gynecomastia in Chinese infants and toddlers, identify the potential risk factors, and explore the influence of early breast development on physical growth, mental development and psychomotor development.

METHODA total of 1 510 full term and healthy children at the age of 0-48 months were sampled by stratified cluster random sampling method from 8 provinces from 2011-2012. Weight, height and breast development were assessed by senior primary pediatricians, while Bayley Scale of Infant Development-I (BSID-I) was used to measure the mental developmental index (MDI) and psychomotor developmental index (PDI) for children aged 2-30 months. Social-demographic Questionnaires were completed by the caregivers.

RESULTThe combined prevalence of premature thelarche and gynecomastia was 1.6% (23/1 475), girls 2.2% (15/695), boys 1.0% (8/780), all within 2 years of age. The birth weight, feeding patterns in first 4 months, delivery mode, weaning time and social economic status were not significantly associated with the breast development. However, lower father's education level (OR = 3.632, 95%CI = 1.565-8.432) as well as smoking mother (OR = 18.960, 95%CI = 1.590-226.304) were significantly related to breast development even after adjusting for potential confounders. Lower weight (-0.479 ± 0.648 vs. 0.005 ± 0.987, P < 0.05) and height (-0.602 ± 1.042 vs. 0.008 ± 0.986, P < 0.05) Z score were found in breast development group, even after adjusting for age, gender and father' education level. Neither mental development (t = -0.082, P > 0.05) nor psychomotor development (t = 1.054, P > 0.05) was associated with breast development.

CONCLUSIONWe showed a similar prevalence of premature thelarche with the data reported in similar studies reported from other countries. Among the 0-48 months old infants and toddlers, Father's education level and smoking mother were both related to breast development. Breast development was significantly associated with physical growth, but had no correlation with the mental or psychomotor development.

African Continental Ancestry Group ; Body Height ; Body Weight ; Breast ; growth & development ; Child Development ; Child, Preschool ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Gynecomastia ; epidemiology ; etiology ; Humans ; Infant ; Infant, Newborn ; Male ; Multivariate Analysis ; Prevalence ; Puberty, Precocious ; epidemiology ; etiology

Objective:To construct a value evaluation framework for high-value medical consumables,providing a guidance for medical insurance access and hospital access management scenarios in China.Methods:It conducted literature review,qualitative in-terviews and quantitative surveys.A total of 12 experts were invited for qualitative interviews,while 100 experts from four fields of health technology assessment,medical insurance,hospital management,and clinical practice participated in the quantitative survey.Through those process,it generated the composition of the value framework and the scoring of each item.Differences in ratings be-tween different scenarios and experts were analyzed through chi-square tests.The recommendation level for each item was graded.Re-sults:A comprehensive value evaluation framework for high-value medical consumables was established,which included 6 core dimen-sions,comprised 16 items for secondary dimensions and 50 items for tertiary dimensions.It showed significant differences between the medical insurance access and hospital access scenarios,as well as among different fields of experts in the same scenario.furthermore,grading the items in two scenarios.The medical insurance access scenario had 8 highly recommended items,and the hospital access scenario had 24 highly recommended items.Conclusion:Value evaluation should encourage multi-dimensional assessments and inter-disciplinary participation,continually improving the management of high-value medical consumables in medical insurance and hospital access.

Drug metabolism and pharmacokinetics (DMPK) are the science to study the process of drug absorption, distribution, metabolism and excretion. It is very important to evaluate the characteristics of DMPK for the early development of drugs and the later clinical precision medication. The innovative construction of DMPK models promotes the development and improvement of drug evaluation system. Based on our research results, this review summarized the latest progress and application of innovative DMPK models, focusing on the following two aspects: (1) CRISPR/Cas9 gene editing rat models, including Cyp2e1

The co-existence of different neurodegenerative diseases in the same case has received increasing attention and reports. A rare comorbidity of amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP) in a sporadic patient was reported. The patient presented with pseudobulbar palsy, freezing gait, and developed muscle weakness and fasciculation. Brain magnetic resonance imaging, positron emission computed tomography and whole exomesequencing showed no evident abnormality. The patient had no response towards the treatment of levodopa, and received supportive treatment and gastrostomy. He is in stable condition by now. Totally 23 cases of ALS with PSP were reviewed, and found that the clinical manifestations were related to the main distribution of pathological inclusion bodies and the location of neuron loss, and the deposition of the same pathological protein in multiple systems may lead to the coexistence of different neurodegenerative diseases. Traditional treatment is generally ineffective, thus support treatment is pivotal. The genetic background and pathogenesis of this comorbidity should be studied in the future.

The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as

Objective: To compare the efficacy of modified pancreaticojejunostomy with traditional pancreaticojejunostomy following pancreaticoduodenectomy, and to investigate the risk factors of postoperative pancreatic fistula. Methods: Clinical data of 68 patients who underwent pancreaticoduodenectomy between October 2017 and October 2018 at the Second Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital was retrospectively collected and analyzed.According to the method of pancreaticojejunostomy, the patients were divided into two groups: modified pancreaticojejunostomy group (34 patients) and traditional pancreaticojejunostomy group (34 patients). There were 18 males and 16 females, aged (60.4±9.6) years of modified pancreaticojejunostomy groups; there were 17 males and 18 females, aged (58.9±10.9) years of traditional pancreaticojejunostomy group. The major postoperative complications such as pancreatic fistula were compared between the two groups, and the risk factors of postoperative pancreatic fistula were analyzed by univariate and multivariate analyses. Results: All of the 68 operations were successfully completed. The overall incidence of postoperative complications was 51.5% (35/68). The incidence of postoperative pancreatic fistula was 13.2% (9/68), of which all were cases of grade B.There were 16 patients (23.5%) occurred with abdominal infection, and 11 patients (16.2%) occurred with delayed gastric emptying, including 1 case of grade A, 1 case of grade B and 9 cases of grade C.And 9 patients (13.2%) occurred with postoperative bleeding was, including 2 cases of mild bleeding, 5 cases of moderate bleeding, and 2 cases of severe bleeding.Biliary leakage occurred in one patient (1.5%) and chylous leakage occurred in two patients (2.9%). The modified pancreaticojejunostomy could significantly reduce the incidence of postoperative bleeding compared with control group (χ²=4.610, P=0.032). And there were no significant differences for other postoperative complications between the two groups (all P>0.05). According to the results of univariate analysis: age, intraoperative bleeding and diameter of pancreatic tube were related factors affecting postoperative pancreatic fistula (P=0.025, 0.019, 0.017, respectively). The results of multivariate analysis showed that intraoperative bleeding>400 ml and diameter of pancreatic tube <3 mm were independent risk factors of pancreatic fistula following pancreaticoduodenectomy (P=0.025, 0.008, respectively). Conclusion The modified pancreaticojejunostomy is feasible with advantages of reducing postoperative bleeding following pancreaticoduodenectomy.

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.