Solid dispersion technology is an advanced technology to improve the solubility and bioavailability of poorly soluble drugs.Inhibition of the recrystallization and amorphous phase separation of amorphous solid dispersion (ASD) active pharmaceutical ingredients are important to ensure product stability,so the characterization of ASD phase separation is essential.Based on the principle of phase separation,this paper analyzed and summarized the advantages,disadvantages and applicability of the various characterization techniques,in order to provide an efficient reference for the characterization and stability study of ASD.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective: To investigate the epidemiological data of an outbreak of influenza A in a primary school in Shanghai, to provide reference for targeted prevention and control measures. Methods: A field epidemiological method was used to investigate and collect the data of influenza A outbreak in a primary school in Jing an District from November 8 to December 6, 2022, through on site follow up and telephone return visit to health teachers and cases. The distribution characteristics of the epidemic were analyzed by descriptive epidemiology. Results: The first case developed symptoms of cough, sore throat, and fever on the morning of November 8th 2022, with a maximum body temperature of 38.6 ℃. Later, the clinical diagnosis was influenza A. The total number of influenza like cases reported in this outbreak is 99, including 92 students and 7 teachers. The total incidence rate was 9.45%. The clinical symptoms of all cases were fever, sore throat, and cough; 27 cases of influenza A were diagnosed by hospital rapid diagnostic reagents. The second grade students had the highest case incidence rate(24.46%), and there was a statistically significant difference in case incidence rates among students of different grades ( χ 2=48.28, P ＜0.01). The case incidence rate on the second floor was the highest (23.47%), and there was a statistically significant difference between the case incidence rates on different floors ( χ 2=52.38, P ＜ 0.01 ). Etiological testing showed that the influenza virus causing this outbreak was type A H3N2 virus. Conclusion This outbreak is a campus cluster outbreak caused by influenza A (H3N2) virus. The health and education departments should strengthen cooperation to effectively implement prevention and control measures of infectious diseases, and timely identify the source of infection and cut off the transmission route.

Non-invasive mechanical ventilation(NIV)is increasingly being used as a respiratory support technique in clinical practice.However,the pressure-related injuries should not be overlooked.In order to prevent local pressure injuries caused by NIV technology,a series of preventive measures have been adopted in clinical work.These measures include the use of dressings to provide pressure relief to the local skin.Currently,in clinical practice,when using preventive dressings,nurses need to cut them themselves based on the physiological structure of the patient's nose,forehead,or face.However,precise cutting can be challenging.If the dressing is cut too small,it may not provide adequate prevention,and if it's cut too large,it can cover too much skin,affecting the nurse's observation and the patient's comfort.Additionally,during NIV treatment,the preventive dressings used may become curled or displaced,requiring nurses to re-cut and replace them.This process inevitably leads to material wastage,increasing the cost of dressing use for patients.Moreover,the cutting tools used must meet infection control requirements,adding to the nursing workload and reducing the compliance of nurses in changing dressings.Our research team has designed a ready-made pressure injury prevention dressing component for use with NIV masks to prevent pressure injuries to the nasal and facial areas.It is precisely designed,flexible in composition,easy to use,and can provide multiple usage modes.It effectively combines emergency care with pressure relief measures,reducing the occurrence of pressure injuries to the patient's nasal and facial areas.This improves patient comfort and treatment compliance,facilitates technology-based nursing,and enhances clinical efficiency.It has significant clinical application value and has been granted a National Utility Model Patent(ZL 202020529121.6).

OBJECTIVE To study the chemical composition and analgesia molecular mechanism of Shuanghu Zhongtongning tincture by UPLC-Q-TOF-MS/MS and network pharmacology. METHODS By comparing the chromatogram and blank chromatogram of Shuanghu Zhongtongning tincture, combined with PubChem, HMDB, MassBank database spectrum and the lysis information of reference substance, the chemical composition of Shuanghu Zhongtongning tincture was analyzed and identified. Protein-protein interaction network was constructed by using STRING database, and potential targets of analgesic effect of Shuanghu Zhongtongning tincture were screened. And GO and KEGG enrichment analysis were performed to analyze the core pathways related to analgesia. The network of "chemical composition-disease-target" was constructed by Cytoscape software to analyze the key compounds related to analgesia. RESULTS Seventeen core components of neochlorogenic acid, chlorogenic acid, hesperidin, neohesperidin, ferulic acid, berberine, ursolic acid, deoxyaconitine, mesaconitine, hypaconitine, benzoylmesaconine, benzoylhypacoitine, caffeic acid, quercetin, oleanolic acid, 4-hydroxycinnamic acid and mefenamic acid were identified, 3 core targets of STAT3, MAPK3 and MAPK1 were found, and 4 key signaling pathways of IL-17, TNF, PI3K-Akt and arachidonic metabolism were revealed. CONCLUSION This study preliminarily clarifies the chemical composition of Shuanghu Zhongtongning tincture and potential mechanism of analgesic effect, and provides a scientific theoretical basis for the study on the material basis and mechanism of Shuanghu Zhongtongning tincture.

Objective:To analyze clinical data of 3 children with LMX1B-associated disease characterized by asymptomatic glomerular proteinuria, thus improving the recognition of asymptomatic proteinuria with genetic causes. Methods:Three patients with LMX1B-associated disease presented with prominent asymptomatic proteinuria diagnosed by the next-generation sequencing in Department of Pediatrics, Peking University First Hospital from April 2014 to October 2017 were included in this study.Clinical data, including renal and extrarenal manifestations, renal biopsy, and family history, were collected and retrospectively analyzed. Results:All 3 children were girls, the age of onset were 2 years, 1 year, and 4 years, respectively, and the diagnosis age were 11 years, 5 years and 6 years, respectively.All of them had glomerular proteinuria, and nephrotic-level proteinuria occurred in one patient.Microscopic hematuria was found in 2 patients.All of them had normal renal function.Only one patient underwent renal biopsy.Electron microscopy of the first time of biopsy revealed segmental thinning of the glomerular basement membrane.Re-biopsy 4 years later showed irregular thickening of the glomerular basement membrane, moth-eaten appearance and collagen fibrillar material deposition.No abnormalities of nails, limbs and joints were observed by physical examination.Two patients had a family history of renal disease.Conclusions:Genetic factors should be considered in children with obscure onset asymptomatic proteinuria without definite clinical causes.Genetic testing can help diagnose and guide treatment as early as possible.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Stereo-electroencephalography (SEEG) is widely used to record the electrical activity of patients' brain in clinical. The SEEG-based epileptogenic network can better describe the origin and the spreading of seizures, which makes it an important measure to localize epileptogenic zone (EZ). SEEG data from six patients with refractory epilepsy are used in this study. Five of them are with temporal lobe epilepsy, and the other is with extratemporal lobe epilepsy. The node outflow (out-degree) and inflow (in-degree) of information are calculated in each node of epileptic network, and the overlay between selected nodes and resected nodes is analyzed. In this study, SEEG data is transformed to bipolar montage, and then the epileptic network is established by using independent effective coherence (iCoh) method. The SEEG segments at onset, middle and termination of seizures in Delta, Theta, Alpha, Beta, and Gamma rhythms are used respectively. Finally, the K-means clustering algorithm is applied on the node values of out-degree and in-degree respectively. The nodes in the cluster with high value are compared with the resected regions. The final results show that the accuracy of selected nodes in resected region in the Delta, Alpha and Beta rhythm are 0.90, 0.88 and 0.89 based on out-degree values in temporal lobe epilepsy patients respectively, while the in-degree values cannot differentiate them. In contrast, the out-degree values are higher outside the temporal lobe in the patient with extratemporal lobe epilepsy. Based on the out-degree feature in low-frequency epileptic network, this study provides a potential quantitative measure for identifying patients with temporal lobe epilepsy in clinical.
Brain Waves ; Electroencephalography ; Epilepsy, Temporal Lobe ; diagnosis ; Humans

Objective To explore the relationship between anxious depression and cortisol rhythm disorder and influencing factors of immune metabolism. And to look for biological markers that can be used for clinical diagnosis and treatment of anxious depression. Methods Totally 43 patients with anxious depres-sion(A-MDD group) and 44 patients with non-anxious depression matched by sex,age and years of education (NA-MDD group)were recruited. Electrochemiluminescence was used to detect the plasma levels of adreno-corticotropic hormone(ACTH),cortisol(COR),c-reactive protein(CRP) and IL-6. Automatic biochemical a-nalysis was used to detect plasma total TC,TG,HDL and LDL. Using logistic regression analysis to discuss the influencing factors of anxiety depression. Results The comparison between the two group showed that the age of first onset,BMI and SBP in the A-MDD group((35. 15±11. 56),(24. 11±3. 03)kg/m2,(130. 09 ±13. 33)mmHg) were significantly higher than those in the NA-MDD group((31. 34± 14. 08),( 22. 70± 3. 19)kg/m2,( 121. 89±12. 49)mmHg)(t=2. 631,2. 009,2. 964,all P<0. 05). The HAMD score and the factor scores of cognitive impairment,change of day and night,delay,sleep disorder and feeling of despair in the A-MDD group((31. 81±5. 39),(8. 03±3. 00),(1. 17±0. 70),(6. 88±1. 93),(4. 44±1. 44),(4. 67± 2. 37)) were significantly higher than those in the NA-MDD group((25. 25±5. 017),(3. 87±3. 12),(0. 79 ±0. 78),(4. 64±2. 22),(3. 34±1. 54),(3. 61±2. 02))(t=2. 297,6. 524,2. 505,5. 210,3. 452,2. 421,all P<0. 05). The plasma TG,CRP and IL-6 levels in the A-MDD group((1. 63±1. 11)mmol/L,(1. 20±0. 77) mg/L,(3. 54±1. 90) pg/L) were significantly higher than those in the NA-MDD group (( 1. 19 ± 0. 66) mmol/L,(0. 933±0. 89)mg/L,(2. 65±1. 34)pg/L) (t=2. 254,2. 250,2. 352,all P<0. 05). The incidence of cortisol disturbance was 72% in the A-MDD group,and 48% in the NA-MDD group,and the difference was statistically significant (χ2=5. 369 P=0. 020). Multivariate Logistic regression found that sleep disorder (β=0. 729,OR=2. 072,95%CI=1. 018-3. 119),IL-6(β=0. 583,OR=1. 792,95%CI=1. 168-2. 748),cog-nitive impairment (β=0. 099,OR=1. 104,95% CI=1. 022-1. 193),cortisol rhythm disorders(β=0. 075, OR=1. 078,95%CI=1. 014-1. 146) were the risk factors for anxious depression. Conclusion Anxious de-pression has a high incidence of cortisol rhythm disorder. The COR and IL-6 may be mediators of cortisol rhythm disorder. IL-6 and cortisol rhythm disorder together with sleep disorder and negative cognition consti-tute maybe high risk factors for anxious depression.

Objective To explore the psychological process of cognitive impairment in patients with recurrent major depression disorder (MDD). Methods Patients with first-episode (n=30) and recurrent MDD (n=68) in the outpatient department of the First Affiliated Hospital of Zhengzhou University from Sep-tember 2016 to December 2017 were collected and healthy controls(n=30) were collected at the same time. According to HAMD-24 score,the group with recurrent attacks was further divided into recurrent attacks-on-set period (n=35) and recurrent attacks-remission period (n=33). All subjects were tested for cognitive function by MATRICS Consensus Cognitive Battery( MCCB). Results (1) In terms of cognitive function assessment,the scores of information processing speed ( 41. 27 ± 8. 44, 37. 00 ± 11. 68), working memory (40. 53±10. 33,41. 26±9. 37),attention/alertness ( 40. 50± 7. 25,39. 58± 8. 23),word learning ( 38. 83± 8. 39,38. 84±9. 57),visual memory(39. 30±14. 03,37. 57±10. 42),reasoning and problem solving(37. 80± 9. 55,38. 78±8. 66),and social cognition (34. 63± 9. 66) in the first-episode group and the recurrent group were lower than those in the control group ( information processing speed ( 48. 23±7. 63),working memory (50. 57±7. 84),attention/alertness (51. 63±7. 41),word learning (45. 57±9. 55),visual memory (50. 57± 8. 42),reasoning and problem solving (50. 03±9. 87) and social cognition (47. 90±19. 01)) (F=12. 818, 12. 173,26. 166,6. 004,15. 085,18. 331,10. 218,P<0. 05); (2) In working memory and social cognition, the difference was statistically significant in the first-episode group,repeated attacks-episodes(working mem-ory:37. 89±9. 15,social cognition:28. 48± 8. 35) and recurrent group-remission( working memory:44. 85± 8. 32,social cognition:40. 44 ± 11. 36, P=0. 010,0. 001). Further comparisons revealed that the score of working memory in repeated attacks-episodes was lower than that in recurrent group-remission (P=0. 003). the score of social cognition in the first-episode group was higher than that in the recurrent-attack period group (P=0. 038). The score of social cognition in the recurrent group-remission was higher than that in re-current-attack period group (P<0. 01). Conclusion There is cognitive impairment in the first episode and the recurrence MDD. The impairment in the recurrent episode is more serious than that in the first episode of depression. The impairment of social cognitive in the recurrent attacks-episodes is more serious than that in the first-episode of depression.