Atom-photon dressed states in a waveguide-QED system with multiple giant atoms.

We study the properties of bound states in waveguide-QED systems consisting of multiple giant atoms coupled to a coupled-resonator waveguide. Based on the general analytical expressions for these states and the corresponding energy spectra, we analyze in detail the threshold conditions for the appearance of bound states and the photon-mediated interactions between dressed atoms for different configurations. In addition, when multiple giant atoms are coupled to the waveguide, different types of interacting atomic chain can be obtained by manipulating the coupling configurations. Accordingly, the energy spectra of the bound states form metaband structures in the photonic band gaps. This makes the system a useful platform for quantum simulation and quantum information processing.

Three-dimensional analysis of mandibular morphology asymmetry and temporomandibular joint position in patients with unilateral Brodie bite.

OBJECTIVE: Previous studies have shown unilateral posterior crossbite is associated with mandibular asymmetry in morphology and position. However, it remains unclear whether unilateral Brodie bite plays a similar role in mandibular development. Therefore, this study aims to investigate the morphological and positional symmetry of mandibles in patients with unilateral Brodie bite by three-dimensional anaylsis. METHODS: Fourteen patients with unilateral Brodie bite (mean age 18.43 ± 4.24 years) and fourteen sex- and age-matched patients with normal occlusion (mean age 18.07 ± 5.48 years) underwent cone-beam computed tomography (CBCT) scans. 3D surface mesh models of their mandibles were established using Mimics Research 19.0. The surface matching percentage was compared between the original and mirrored mandible by Geomagic Control X software. Furthermore, the dimension and position of the temporomandibular joint (TMJ) were determined for both groups using InVivoDental 5.0. RESULTS: For surface-to-surface deviation analysis, the percentage of mismatch in patients with unilateral Brodie bite was significantly higher than the control group at ±0.50 mm, ±0.75 mm, and ±1.00 mm tolerance (P < .001). In patients with unilateral Brodie syndrome, the condyles on the scissors-bite side showed a significantly more anterior position (P = .03), greater medial inclination (P < .01), and larger posterior TMJ space (P = .01) than the non-scissors-bite side. CONCLUSION: Patients with unilateral Brodie bite exhibit a more asymmetrical mandibular morphology, with a greater anterior condylar position and posterior joint space on the scissors-bite side, indicating that early diagnosis and treatment may be necessary for patients with unilateral Brodie bite.

[Wolfram-like syndrome: a case report].

Different from classical autosomal recessive Wolfram syndrome, Wolfram-like syndrome is an autosomal dominant disorder caused by a heterozygous mutation in the WFS1 gene. In this case, a 7-year-old male child presented to the eye clinic due to vision loss that could not be corrected, discovered during a routine examination. The child had experienced hearing impairment since early childhood, leading to cochlear implantation. Ophthalmic examination revealed optic disc atrophy in both eyes. Optical coherence tomography imaging demonstrated a distinctive thickening of the outer plexiform layer with abnormal layering, characteristic of a single mutation in the WFS1 gene. Subsequent genetic testing identified a de novo heterozygous missense mutation c.2051C>T (p.A684V) in the WFS1 gene, which ultimately led to the diagnosis of Wolfram-like syndrome.

Single-photon switches, beam splitters, and circulators based on the photonic Aharonov-Bohm effect.

Single-photon devices such as switches, beam splitters, and circulators are fundamental components to construct photonic integrated quantum networks. In this paper, two V-type three-level atoms coupled to a waveguide are proposed to simultaneously realize these functions as a multifunctional and reconfigurable single-photon device. When both the two atoms are driven by the external coherent fields, the difference in the phases of the coherent driving induces the photonic Aharonov-Bohm effect. Based on the photonic Aharonov-Bohm effect and setting the two-atom distance to match the constructive or destructive interference conditions among photons travelling along different paths, a single-photon switch is achieved since the incident single photon can be controlled from complete transmission to complete reflection by adjusting the amplitudes and phases of the driving fields. When properly changing the amplitudes and phases of the driving fields, the incident photons are split equally into multiple components as a beam splitter operated with different frequencies. Meanwhile, the single-photon circulator with reconfigurable circulation directions can also be obtained.

Brown goat yogurt: Metabolomics, peptidomics, and sensory changes during production.

Brown goat milk products have gained popularity for their unique taste and flavor. The emergence of chain-reversal phenomenon makes the design and development of goat milk products gradually tend to a consumer-oriented model. However, the precise mechanism of how browning and fermentation process causes characteristics is not clear. In an effort to understand how the treatments potentially lead to certain metabolite profile changes in goat milk, comprehensive, quantitative metabolomics and peptidomics analysis of goat milk samples after browning and fermentation were undertaken. An intelligent hybrid z-score standardization-principal components algorithm-multimodal denoizing autoencoder was used for feature fusion and hidden layer fusion in high-dimensional variable space. The fermentation process significantly improved the flavor of brown goat yogurt through the tricarboxylic acid-urea-glycolysis composite pathway. Bitter peptides HPFLEWAR, PPGLPDKY, and PPPPPKK have strong interactions with both putative dipeptidyl peptidase IV and angiotensin-converting enzyme, proving that brown goat yogurt can be considered as effective provider of potential putative dipeptidyl peptidase IV and angiotensin-converting enzyme inhibitors. The level of health-promoting bioactive components and sensory contributed to consumer selection. The proposed multimodal data integrative analysis platform was applicable to explain the effect of the dynamic changes of metabolites and peptides on consumer preferences.

Efficacy and safety of methylene blue injection for intractable idiopathic pruritus ani: a single-arm metaanalysis and systematic review.

PURPOSE: To evaluate how effective methylene blue injection was at treating intractable idiopathic pruritus ani. METHODS: A comprehensive literature search of the PubMed, Embase, Cochrane library, and Web of Science databases was conducted. All clinical studies (prospective and retrospective) that evaluated the efficacy of methylene blue in treating intractable idiopathic pruritus ani were included. Studies that reported the resolution rate, after a single injection and after a second injection, the recurrence rate, symptom scores, and transient complications of methylene blue injections in treating intractable idiopathic pruritus ani were included. RESULTS: The seven selected studies included 225 patients with idiopathic pruritus ani. The resolution rates after a single injection and after a second injection was 0.761 (0.649-0.873, P < 0.01, I2 = 69.06%) and 0.854 (0.752-0.955, P < 0.01, I2 = 77.391%), respectively, the remission rates at 1, 3, and 5 years were 0.753 (0.612-0.893, P < 0.001), 0.773 (0.675-0.871, P < 0.001) and 0.240 (0.033-0.447, P < 0.001), respectively, the effect value of the merger was 0.569 (0.367-0.772, P < 0.001, I2 = 79.199%), and the recurrence rates at 1, 2, 3, and < 1 year were 0.202 (0.083-0.322, P < 0.001), 0.533 (0.285-0.781, P < 0.001), 0.437 (-0.044, 0.917, P < 0.001) and 0.067 (0.023-0.111, P < 0.001), respectively. The effect value of the merger was 0.223 (0.126-0.319, P < 0.001, I2 = 75.840). CONCLUSION: Using methylene blue injections to treat intractable idiopathic pruritus ani is relatively efficacious, resulting in a relatively low recurrence rate and no severe complications. However, the available literature was of poor quality. Therefore, higher quality studies are necessary to confirm that methylene blue injection is efficacious for pruritus ani, such as a randomized prospective multicenter studies.

[Association between remnant cholesterol levels and incident diabetic retinopathy in middle-aged and older patients with diabetes].

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

[Efficacy and safety of ultra rapid lispro in the treatment of type 2 diabetes mellitus: a randomized controlled clinical trial].

Objective: To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus. Methods: This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A1c (HbA1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher's exact test. Results: Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient-year; P=0.040]. Conclusions: With good glycemic control, URLi showed non-inferiority for HbA1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.

[Analysis of prognosis and related factors in oldest-old patients with left-side or right-side colon cancer after hemicolectomy].

Objective: This study aimed to explore the difference of prognosis in oldest-old colon cancer patients between the left-side and right-side hemicolectomy. Methods: A total of 238 oldest-old (≥75 years old) colon cancer patients who received surgical treatment in Gastrointestinal Surgery Department of Beijing Hospital from December 2010 to December 2020 were retrospectively collected. They were divided into right-side hemicolectomy (RCC) group (130 cases) and left-side hemicolectomy (LCC) group (108 cases) by surgical methods. The difference in postoperative short-term complications and long-term prognosis was compared between the two groups, and the related factors of postoperative death was analyzed using multivariate Cox regression model. Results: The age of 238 oldest-old patients with colon cancer ranged from 75 to 93 years old (80.5±3.7). There were 128 males and 110 females. The ages of patients in the LCC group and RCC group were (80.4±3.7) and (80.6±3.7) years old (P=0.699), respectively. There was no significant difference in gender, body mass index (BMI) and co-existing chronic diseases between two groups (P>0.05). The proportion of the duration of surgery exceeding 170 min in the LCC group was significantly higher than that in the RCC group (56.5% vs 43.1%, P=0.039). The incidence of postoperative short-term complications in RCC group was slightly higher than LCC group (P>0.05), and there was no significant difference in overall survival (OS), tumor-specific survival (CSS) and disease-free survival (DFS) between two groups. However, the two groups had different prognostic risk factors, pathological Ⅳ stage (HR=28.970,95%CI:1.768-474.813,P=0.018), intraoperative bleeding (HR=2.297,95%CI:1.351-3.907,P=0.002) and cancer nodules (HR=2.044,95%CI:1.047-3.989,P=0.036) were independent prognostic risk factors in LCC group. Underweight (HR=0.428,95%CI:0.192-0.955,P=0.038), overweight(HR=0.316,95%CI:0.125-0.800,P=0.015),obesity (HR=0.211,95%CI:0.067-0.658,P=0.007), lymph node metastasis (HR=2.682,95%CI:1.497-4.807,P=0.001), tumor nodule (HR=2.507,95%CI:1.301-4.831,P=0.027) and postoperative length of stay of 9 days (HR=1.829,95%CI:1.070-3.128,P=0.006) were independent risk factors for poor prognosis in RCC group. Conclusions: The duration of surgery of oldest-old colon cancer patients in the LCC group was longer than that in the RCC group. However, there was no significant difference in the incidence of postoperative complications between the two groups. High pathological stage, more intraoperative bleeding and cancer nodules were independent prognostic risk factors in the LCC group. Abnormal BMI, lymph node metastasis, cancer nodules and postoperative length of stay were independent risk factors for poor prognosis in the RCC group.

[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia.

Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.

[Cardiometabolic disease patterns among elderly patients with colorectal cancer in China].

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.

[Association between nutritional status and depression among centenarians in Hainan Province].

Objective: To explore the relationship between nutritional status and depression of centenarians in Hainan Province. Methods: A total of 1 002 elderly people in Hainan Province who were 100 years of age or older on June 1, 2014 were included in the study. The basic condition questionnaire, Mini Nutritional Assessment Short-Form (MNA-SF), Instrumental Activities of Daily Living-Lawton scale (Lawton-IADL) and Geriatric Depression Scale (GDS-15) were used to collect the subjects' demographic characteristics, disease history, nutritional status, functional status of daily activities, and depression, respectively. The restricted cubic spline fitting logistic regression model was used to analyze the relationship between the scores of MNA-SF and depression. The multivariable logistic regression model was used to analyze the relationship between nutritional status and depression in the total population and different subgroups of daily activity function. Results: The M (Q1, Q3) of subjects' age was 102 (101, 104) years old, among which 82.0% (822) were women. The prevalence of malnutrition, impaired daily activities, and depression was 20.8% (208 cases), 64.7% (648 cases) and 28.5%(286 cases), respectively. Restricted cubic spline fitting logistic regression model showed a linear association between the scores of the MNA-SF and depression (P=0.251). The higher the MNA-SF score was, the lower the risk of depression was in centenarians. Multivariable logistic regression model analysis showed that after adjusting for sex, education level, diabetes, hypertension, coronary heart disease, visual function, hearing function, and functional status of daily activities, malnutrition was positively associated with the development of depression in the total population and the subgroup with impaired daily activities [OR (95%CI) was 1.50 (1.07-2.11) and 1.56 (1.09-2.24), respectively], but not in the subgroup with good daily activities [OR (95%CI): 0.77 (0.21-2.80)]. Conclusion: Malnutrition is positively associated with depression, especially in the centenarians with impaired daily activities.

Depressive symptoms in Chinese adults with risk factors for diabetes: the Shanghai High-Risk Diabetic Screen (SHiDS) study.

AIMS: To evaluate the relationship between newly diagnosed diabetes or prediabetes and depressive symptoms among individuals with risk factors for diabetes in China. We also investigated the associations of depressive symptoms with pancreatic ß-cell function and insulin resistance. METHODS: We used cross-sectional data from the Shanghai High-Risk Diabetic Screen (SHiDS) project. Between 2014 and 2017, a total of 1728 participants were enrolled in this study and underwent an oral glucose tolerance test to screen for diabetes and prediabetes. Insulin resistance was evaluated using the homeostatic model assessment of insulin resistance and the modified Matsuda index. Pancreatic ß-cell function was calculated using the homeostatic model assessment of ß-cell function, Stumvoll first- and second-phase indexes. Elevated depressive symptoms were determined using the Patient Health Questionnaire-9 (PHQ-9 score ≥ 10). RESULTS: The prevalence of elevated depressive symptoms in the total study population was 4.8% (83 of 1728). Compared with the normal glucose tolerance group, individuals with newly diagnosed diabetes were less likely to have elevated depressive symptoms even after controlling for potential confounders [adjusted odds ratio (OR) 0.35, 95% confidence interval (CI) 0.18-0.68; P = 0.002]. However, prediabetes was not associated with depressive symptoms. The odds for elevated depressive symptoms were increased in individuals with higher levels of the Stumvoll first-phase index. No association was observed between depressive symptoms and insulin resistance. CONCLUSION: Elevated depressive symptoms were less prevalent in Chinese individuals with newly diagnosed diabetes among a high-risk population for diabetes.

Antifungal activity screening for mint and thyme essential oils against Rhizopus stolonifer and their application in postharvest preservation of strawberry and peach fruits.

AIMS: With a goal to identify specific essential oils that can control postharvest Rhizopus rot on strawberry and peach fruits, we performed screening for 26 essential oils based on their antifungal activity against Rhizopus stolonifer in vitro and investigated the underlying mechanism. METHODS AND RESULTS: Mentha spicata (Ms), Mentha piperita (Mp), Thymus vulgaris CT carvacrol (Tc) and Thymus vulgaris CT thymol (Tt) exhibited strong inhibition on R. stolonifer growth in the screening. These essential oils increased plasma membrane permeability of R. stolonifer and resulted in the outflow of intercellular electrolyte, nucleic acid, protein and soluble sugar. Morphology of R. stolonifer mycelia was greatly altered by these essential oils. Hyphae treated by these essential oils exhibited high accumulation of superoxide anion and malonaldehyde. Combination of these essential oils in commercial package reduced Rhizopus rot on strawberry and peach fruits, with Mp showing the strongest efficiency. CONCLUSION: Ms, Mp, Tc and Tt essential oils inhibited R. stolonifer growth by targeting its plasma membrane and reduced Rhizopus rot on strawberry and peach fruits. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides potential applications of natural plant extract, as alternatives to tradition fungicides, to control postharvest decay on fruits and vegetables.

[Correlation between intrahepatic triglyceride content quantified by proton magnetic resonance spectroscopy and glucose metabolism].

Objective: To investigate the correlation between intrahepatic triglyceride content (IHTC) and glucose metabolism in patients with non-alcoholic fatty liver disease (NAFLD) diagnosed by proton magnetic resonance spectroscopy (1H-MRS). Methods: A total of 239 subjects without diabetes mellitus were previously enrolled and underwent 1H-MRS scans. Anthropometric indexes including height, weight, waist and blood pressure, and laboratory findings as plasma glucose (PG), insulin (INS), C-peptide (CP), liver enzymes [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (GGT)] and lipid profiles were collected. According to IHTC levels, participants were divided into three groups: the non-NAFLD group (IHTC<5.56%), the mild NAFLD group (IHTC 5.56%-<33%), and the moderate and severe NAFLD group (IHTC ≥ 33%). The clinical characteristics of each group were analyzed, and the correlation between IHTC and glucose metabolism were assessed. Results: Compared with those in the non-NAFLD group, male proportion, waist, 120 min postprandial PG (PG120), CP, liver enzymes and total cholesterol (TC) levels were greater in the NAFLD group, whereas insulin sensitivity index-Cederholm (ISI-Cederholm) and high density lipoprotein cholesterol (HDL-C) levels were lower in the NAFLD groups. Subjects in the moderate and severe NAFLD group had higher levels of 120 min postprandial INS (INS120) and Stumvoll indexes, and lower ISI-Cederholm than those in the mild NAFLD group [80.37 (57.68, 112.70) mU/L vs.110.50(71.78, 172.80)mU/L, 1453(1178, 1798)vs.1737(1325, 2380), 358(297, 446) vs.441(318, 594), 2.27(2.01, 2.53) vs.2.06(1.81, 2.39), respectively, all P<0.05]. Correlation analyses showed that IHTC was significantly positively correlated with waist hip ratio (WHR), PG120, INS120, HOMA insulin resistance (HOMA-IR), Stumvoll 1st-insulin secretion, Stumvoll 2nd-insulin secretion, ALT, AST, GGT and TC (r=0.197, 0.274, 0.334, 0.162, 0.199, 0.211, 0.406, 0.361, 0.215, and 0.196, respectively, all P<0.05), and negatively correlated with ISI-Cederholm and HDL-C (r=-0.334, and-0.237, respectively, all P<0.05). Furthermore, a multiple linear stepwise regression analysis indicated that ISI-Cederholm (Standardized ß =-0.298, P<0.001) and Stumvoll 1st insulin secretion (Standardized ß = 0.164, P = 0.024) were independent factors of IHTC. Conclusions: Peripheral insulin resistance occurs in the early stage of NAFLD and becomes worse with the progression of the disease. IHTC was independently associated with insulin sensitivity and first-phase insulin secretion.

[Comparison of efficacy and safety of insulin aspart injection Rishulin and NovoRapid for treatment of diabetes: a multicenter, randomized, open-labeled, controlled trial].

Objective: To compare the efficacy and safety of Tonghua Dongbao's insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes. Methods: A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment. Results: For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% (P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % (P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95%CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% (P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% (P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L (P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L (P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group (P=0.320). Ratios of negative to positive were 7.43% and 10.61% (P=0.360), and ratios of positive to negative were 10.40% and 7.58% (P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% (P=0.371), and the incidence of adverse events was 76.60% and 77.70% (P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions: Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

[Clinical study of dienogest in the treatment of refractory endometriosis-associated pain].

Objective: To evaluate the efficacy and safety of dienogest (DNG) in the treatment of refractory endometriosis-associated pain (REAP). Methods: In this study, REAP was defined according to the following criteria: (1) the pain duration was ≥12 months and visual analogue scale (VAS)≥60 mm; (2) the previous treatments with over two medicines like oral contraceptives and levonorgestrel-releasing intrauterine system failed to achieve satisfactory relief of pain, with VAS reduction less than 50%; with gonadotropin-releasing hormone agonist or mifepristone, the pain could be controlled temporarily, but it recurred after discontinuation of medicines; (3) the pain could not be relieved by surgery or even repeated surgeries. In the present study, 48 patients with REAP were treated with DNG 2 mg/day orally and the clinical outcomes were retrospectively analyzed. The VAS scores, levels of CA125, estradiol, FSH, LH and changes in the size of endometriotic lesions before and after treatment were compared respectively. The side effects were also analyzed. Results: The average duration of DNG treatment was (20.1±12.8) months. After 3 months of medication, the VAS score was significantly reduced from (77.9±15.8) mm to (20.8±10.7) mm (P<0.01), and CA125 level was significantly reduced from (95±139) kU/L to (38±45) kU/L (P<0.05). The effects were maintained with continuation of DNG treatment. Endometriotic lesions tended to shrink, after 12 months of DNG treatment, the size of ovarian endometriomas was reduced significantly from (3.1±1.0) cm to (1.9±1.2) cm (P<0.05). The mean level of estradiol was maintained at 124.82-221.04 pmol/L and levels of FSH and LH did not change significantly during the treatment. The major side effect was irregular bleeding (75%, 36/48). Conclusions: DNG could effectively relieve REAP and is a well-tolerated therapy. It may supply an alternative option for patients with REAP.

[Identification of Synthetic Cannabinoid 5F-EDMB-PICA in Suspicious Herbal Products].

ABSTRACT: Objective To study the qualitative analysis strategy for unknown synthetic cannabinoid in the suspicious herbal product when no reference substance is available. Methods The synthetic cannabinoid in herbal blend was extracted with methanol. The extract was concentrated by rotary evaporator and separated and purified by preparative liquid chromatography, to obtain high purity synthetic cannabinoid sample. Gas chromatography-mass spectrometry （GC-MS）, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF-MS） and nuclear magnetic resonance （NMR） were used to determine the structure of the prepared compound. Results High purity unknown sample （10 mg） was obtained by preparative liquid chromatography. The sample was analyzed by GC-MS, UPLC-TOF-MS and NMR, and through spectrum analysis, the unknown synthetic cannabinoid was determined as 5F-EDMB-PICA. Conclusion The method to extract unknown synthetic cannabinoid from low content herbal products by preparative liquid chromatography was established, and the structure of the unknown sample was identified by comprehensive use of GC-MS, UPLC-QTOF-MS and NMR. The information will assist forensic laboratories in identifying this substance or other compounds with similar structures in their casework.

[Determination of Salt Forms of New Psychoactive Substances by Ion Chromatography].

ABSTRACT: Objective To establish an ion chromatography method for the salt form determination of new psychoactive substances （NPS）. Methods The method of conducting qualitative and quantitative analysis of six types of organic acid ions （acetate ion, tartrate ion, maleate ion, oxalate ion, fumarate ion, citrate ion） and five types of inorganic anions （fluoride ion, chloride ion, nitrate ion, sulfate ion, phosphate ion） in NPS sample by ion chromatography was developed. The salt forms of 222 seized NPS samples （103 samples with synthetic cannabinoids, 81 samples with cathinones, 44 samples with phenylethylamines, 12 samples with tryptamines, 7 samples with phencyclidines, 6 samples with piperazines, 2 samples with aminoindenes, 26 samples with fentanyls and 43 samples with other types of NPS） were analyzed by this method. Results Each anion had good linearity in the corresponding linear range, the correlation coefficients （r） were greater than 0.999, the limits of detection were 0.01-0.05 mg/L, and the limits of quantitative were 0.1-0.5 mg/L. Except that 5F-BEPIRAPIM was hydrochloride, the salt forms of the other 102 synthetic cannabinoids were all base. The salt form of 81 cathinone samples, 44 phenylethylamine samples, 7 phencyclidine samples and 2 aminoindene samples were all hydrochloride. The salt forms of tryptamine samples included base, hydrochloride, fumarate and oxalate. The salt forms of piperazine samples included base and hydrochloride. The salt forms of fentanyl samples and samples of other types included base, hydrochloride and citrate. Conclusion Ion chromatography is a simple, accurate and efficient method for determining the salt form of NPS samples, which makes the qualitative and quantitative conclusions of NPS more scientific and rigorous.