Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Objective To investigate the impact of propofol(Pro)on high glucose(HG)-induced myocardial cell injury through autophagy mediated by forkhead box O1(Fox O1)/thioredoxininteracting protein(TXNIP)signaling pathway.Methods H9c2 cells were divided into blank group(5.5 mmol·L-1 glucose),high glucose(HG)group(30 mmol·L-1 glucose),HG+Pro group(30 mmol·L-1 glucose+25 μmol·L-1 Pro),HG+Pro+negative control(OE NC)group(first transfected with OE NC,then treated with 30 mmol·L-1 glucose+25 μmol·L-1 Pro),HG+Pro+Fox O1 overexpression plasmid(Fox O1-OE)group(first transfected with Fox O1-OE,then treated with 30 mmol·L-1 glucose+25 μmol·L-1 Pro).Cell counting kit-8(CCK-8)method,TdT-mediated dUTP nick end labeling(TUNEL)method,enzyme-linked immunosorbent assay(ELISA),transmission electron microscope and Western blot were applied to detect the cell survival rate,apoptosis rate,superoxide dismutase(SOD)and malondialdehyde(MDA)levels in the supernatant,and the changes in Autophagosome,Fox O1/TXNIP and autophagy protein expression levels.Results The cell viabilities of blank group,HG group,HG+Pro group,HG+Pro+OE NC group and HG+Pro+Fox O1-OE group were(100.00±0.00)％,(48.15±4.82)％,(79.66±7.98)％,(78.89±7.91)％and(49.22±4.93)％,respectively;the apoptosis rates were(12.04±1.21)％,(42.34±4.25)％,(26.22±2.63)％,(27.02±2.71)％,(38.29±3.86)％,respectively;SOD levels were(62.24±6.25),(28.21±2.85),(55.37±5.58),(55.09±5.53),(30.66±3.08)U·mg-1 pro,respectively;MDA levels were(0.38±0.04),(1.43±0.15),(0.67±0.07),(0.72±0.08)and(1.34±0.14)U·mg-1 pro,respectively;the number of autophagosomes was 6.24±0.63,13.05±1.32,8.31±0.84,8.55±0.86 and 12.22±1.23,respectively;phosphorylated Fox O1(p-Fox O1)/Fox O1 ratios were expressed as 0.34±0.04,0.86±0.09,0.48±0.05,0.43±0.05 and 0.74±0.08;TXNIP were expressed as 0.24±0.03,0.62±0.08,0.38±0.04,0.36±0.04 and 0.58±0.06;Bcelin-1 were expressed as 1.12±0.12,0.53±0.06,1.02±0.11,1.05±0.11 and 0.62±0.07;p62 were expressed as 0.56±0.06,1.56±0.16,0.82±0.09,0.86±0.09 and 1.44±0.15;there were statistical differences in the above indexes between HG group and blank group,HG+Pro group and HG group,HG+Pro+Fox O1-OE group and HG+Pro+OE NC group(all P＜0.05).Conclusion Pro inhibits autophagy by inhibiting Fox O1/TXNIP signaling pathway,and improves HG-induced myocardial cell injury.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To explore the characteristics of the immunophenotypic expression of bone marrow monocytes (M ) and its clinical significance in patients with multiple myeloma (MM ). Methods:The monocyte immunophenotypes expression of 67 MM and 30 anemic patients (control group)were detected by flow cytometry.The immunophenotypes that exhibited statistical differences from the control group were screened out.Further univariate and multivariate regression was used analyze the risk factors affecting the prognosis. The effect of monocyte immunophenotype on the prognosis of MM was analyzed.The correlation of CD38+monocytes with clinical features was explored.Results:The percentages of CD138+monocytes (CD138+M％),CD27+monocytes (CD27+M％),and CD56+monocytes (CD56+M％)in the MM group were significantly higher than that in the control group(P<0.05),but the percentages of CD38+monocytes (CD38+M％)and HLA-DR+monocytes (HLA-DR+M％)were significantly lower than that in the control group (P<0.01 ).The median progression-free survival (PFS)was shorter in the low CD38+monocyte proportion (LCD38+M％)group compared to the high CD38+monocyte proportion (HCD38+M％) group.Additionally,the median overall survival (OS)was significantly shorter in the low CD138+monocyte proportion (LCD138+M％),low CD27+monocyte proportion (LCD27+M％),low CD38+monocyte proportion (LCD38+M％),and low HLA-DR+monocyte proportion (LHLA-DR+M％)groups.Cox regression analysis showed that the low CD38+M％ was an independent risk factor for OS.The LCD38+M％group had significantly higher proportions of involved/uninvolved free light chain ratios ≥100 and 1q21+compared to the HCD38+M％ group (P<0.05 ). Moreover,the proportion of CD38-myeloma cells was significantly higher in the LCD38+M％ group than that in the HCD38+M％ group (P<0.05).Conclusion:The expression of CD38+monocytes in bone marrow of MM patients is closely related to the prognosis and clinical characteristics.CD38+monocytes maybe used to predict prognosis and guide treatment decisions.

Objective:To observe any effect of combining repetitive peripheral magnetic stimulation (rPMS) with repeated transcranial magnetic stimulation (rTMS) on upper limb dysfunction after a stroke.Methods:A total of 128 stroke survivors were randomly divided into a control group, a central group, a peripheral group and a combined group, each of 32. In addition to conventional medical treatment and rehabilitation training, the combined group were given 1Hz rTMS over the M1 area of the unaffected hemisphere and rPMS on the Erb point of the affected upper limb. The central group were given rTMS with sham rPMS, the peripheral group was given rPMS and sham rTMS, while the control group received sham rTMS and sham rPMS. Both the rPMS and rTMS, genuine and sham, were administered once daily for 15 minutes each time, 6 days a week for 4 consecutive weeks. Before and after the treatment, the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT) were administered to evaluate the upper limb motor function of the subjects′ affected side. The Modified Barthel index (MBI) quantified their ability in the activities of daily life.Results:After the intervention, the average FMA-UE, WMFT and MBI scores had improved significantly in all four groups. After the intervention the average FMA-UE, WMFT and MBI scores of the combined, central and peripheral groups were all significantly better than the control group′s averages, with those of the combined group significantly superior to the central and peripheral groups.Conclusion:Both rTMS and rPMS can promote the recovery of upper limb motor function after a stroke and ability in daily life activities. Their combination can achieve better effects.

A rich diversity of wild medicinal plant resources is distributed in China, but the breeding of new plant varieties of Chinese medicinal plants started late and the breeding level is relatively weak. Chinese medicinal plant resources are the foundation for new varieties breeding, and the plant variety rights(PVP) are of great significance for the protection and development of germplasm resources. However, most Chinese medicinal plants do not have a distinctness, uniformity, and stability(DUS) testing guideline. The Ministry of Agriculture and Rural Affairs has put 191 plant species(genera) on protection lists, of which only 30 are medicinal species(genera). At the same time, only 29 of 293 species(genera) plants in the Protection List of New Plant Varieties of the People's Republic of China(Forest and Grass) belong to Chinese medicinal plants. The number of PVP applications and authorization of Chinese medicinal plants is rare, and the composition of variety is unreasonable. Up to now, 29 species(genera) of DUS test guidelines for Chinese medicinal plants have been developed. Some basic problems in the breeding of new varieties of Chinese medicinal plants have appeared, such as the small number of new varieties and insufficient utilization of Chinese medicinal plant resources. This paper reviewed the current situation of breeding of new varieties of Chinese medicinal plants and the research progress of DUS test guidelines in China and discussed the application of biotechnology in the field of Chinese medicinal plant breeding and the existing problems in DUS testing. This paper guides the further application of DUS to protect and utilize the germplasm resources of Chinese medicinal plants.
Agriculture ; Biotechnology ; Plant Breeding ; Plants, Medicinal/genetics*

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m² group (P_interaction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans ; Male ; Arsenic/urine* ; Creatinine ; East Asian People ; Testosterone/blood* ; Urinalysis ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.
Humans ; Influenza, Human ; Sentinel Surveillance ; Syndrome ; China ; Cell Phone

Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.
Humans ; Staphylococcus aureus/genetics* ; Methicillin-Resistant Staphylococcus aureus/genetics* ; Multilocus Sequence Typing ; Phylogeny ; Staphylococcal Infections/epidemiology* ; China/epidemiology*