The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control ; Humans ; Drugs, Chinese Herbal/chemistry*

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective To explore the impact of contrast agent concentration on the excimer laser's effect on plaque ablation.Methods Using a laser catheter with a diameter of 0.9 mm,we conducted plaque model ablation experiments employing a 308-nanometer xenon chloride excimer laser.During the excimer laser ablation process,five groups were formed based on the injected contrast agent concentrations:a saline group,25%concentration group,50%concentration group,75%concentration group,and 100%concentration group.Optical coherence tomography was utilized to assess the changes in plaque lumen area after excimer laser ablation,evaluating the impact of contrast agent concentration on the excimer laser's ablation efficacy.Simultaneously,a water manometer was used to measure the shockwave pressure generated by the excimer laser in liquids with different contrast agent concentrations,aiming to explore the correlation between the shockwave pressure of the excimer laser and its ablative effect.Results The ablation areas in the 75%concentration group and the 100%concentration group were similar(P＞0.05),both exceeding those in the 50%concentration contrast agent group,25%concentration group,and saline group(all P＜0.001).Specifically,the ablation area in the 50%concentration group was significantly larger than that in the 25%concentration group and saline group(both P＜0.001),while the 25%concentration group was larger than the saline group(P＜0.001).The influence of contrast agent concentration on the shockwave pressure of the excimer laser exhibited a similar trend.Additionally,there was a significant positive correlation between the shockwave pressure generated by the excimer laser and its ablation area(r=0.9987,P＜0.001).Conclusions The intensity of excimer laser ablation on plaque tissue can be modulated by altering the contrast agent concentration.These findings offer guidance for the application of excimer laser in conjunction with contrast agent injection techniques in the treatment of coronary artery disease.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: To trace and characterize the whole genome of SARS-CoV-2 of confirmed cases in the outbreak of COVID-19 on July 31, 2021 in Henan Province. Method: Genome-wide sequencing and comparative analysis were performed on positive nucleic acid samples of SARS-CoV-2 from 167 local cases related to the epidemic on July 31, 2021, to analyze the consistency and evolution of the whole genome sequence of virus. Results: Through high-throughput sequencing, a total of 106 cases of SARS-CoV-2 whole genome sequences were obtained. The results of genome analysis showed that the whole genome sequences of 106 cases belonged to the VOC/Delta variant strain (B.1.617.2 clade), and the whole genome sequences of 106 cases were shared with the genomes of 3 imported cases from Myanmar admitted to a hospital in Zhengzhou. On the basis of 45 nucleotide sites, 1-5 nucleotide variation sites were added, and the genome sequence was highly homologous. Conclusion: Combined with the comprehensive analysis of viral genomics, transmission path simulation experiments and epidemiology, it is determined that the local new epidemic in Henan Province is caused by imported cases in the nosocomial area, and the spillover has caused localized infection in the community. At the same time, it spills over to some provincial cities and results in localized clustered epidemics.
Humans ; COVID-19 ; SARS-CoV-2/genetics* ; Genome, Viral ; Epidemics ; Phylogeny

Objective: To summarize the clinical characteristics, diagnosis and treatment of forest encephalitis, and provide basis for revising relevant diagnostic criteria. Methods: From January to December 2020, the clinical characteristics, diagnosis and treatment of forest encephalitis cases in the data of China National Knowledge Infrastructure (CNKI) and Wanfang Chinese journals from 2009 to 2020 were retrospectively analyzed. The measurement data are expressed in Mean±SD, numbers, and the counting data of gender, region and occupation are expressed in numbers and composition ratio. Descriptive analysis of relevant data is carried out. Results: There were 1 153 confirmed cases of forest encephalitis reported in domestic literature, including 910 males and 243 females. Age: 16-78 years old; Cases were mainly distributed in Jilin Province, Inner Mongolia Autonomous Region and Heilongjiang Province. The cases included forest rangers (112/518), freelancers (104/518) and loggers (88/518). The common symptoms and signs were fever 81.2% (936/1153), headache 70.3% (811/1153), meninges irritation 29.0% (334/1153), vomiting 25.3% (292/1153), nausea 21.8% (251/1153), etc. Only 48.1% (555/1153) of the patients obtained positive pathogenic test results from blood and/or cerebrospinal fluid specimens. 42.1% (485/1153) had definite diagnosis grade, 354 cases were mild, 58 cases were moderate, and 73 cases were severe. Among 730 patients with forest encephalitis who received complete treatment, 511 cases were cured, 148 cases were improved, 48 cases were not cured, and 23 cases died. Conclusion: The epidemic of forest encephalitis has strict regional, seasonal and occupational characteristics. Early diagnosis and treatment can reduce the mortality and disability rate.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Retrospective Studies ; Encephalitis, Tick-Borne ; Encephalitis/epidemiology* ; Headache ; Fever

OBJECTIVES: To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification. METHODS: Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model. RESULTS: A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination (R²) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively. CONCLUSIONS The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.
Male ; Humans ; Female ; Neural Networks, Computer ; Software ; Wounds, Nonpenetrating ; Forensic Medicine