Objective To explore the correlation between healthcare-associated infection(HAI)and partial inde-xes in the diagnosis-related groups(DRGs)of patients in thoracic surgery intensive care unit(ICU).Methods DRGs,case mix index(CMI),relative weight(RW),and HAI of patients in thoracic surgery ICU and four subspe-cialty departments(pulmonary surgery group,esophageal surgery group,mediastinum group[mainly thymic sur-gery],and trachea group)in a tertiary chest hospital in Shanghai from January to December 2022 were retrospec-tively analyzed and compared through DRGs index grouping.Results A total of 1 429 patients in the department of thoracic surgery ICU were analyzed,including 59 HAI cases,with a HAI rate of 4.13％.The incidences of HAI in pulmonary surgery group,esophageal surgery group,mediastinum group and trachea group were 3.74％(30/803),5.84％(25/428),1.27％(2/157)and 4.88％(2/41),respectively.There was no statistically significant differ-ence in the incidences of HAI among different subspecialty groups(P＞0.05).A total of 35 DRGs were involved,with CMI of 2.75,3.41,2.35 and 1.25 in pulmonary surgery group,esophageal surgery group,mediastinum group and trachea group,respectively,and RW ranged from 0.53 to 12.62.In the pulmonary surgery group,inci-dence of HAI in male patients was higher than that in female patients.Higher RW score level was associated with higher incidence of HAI.Differences were all statistically significant(all P 0.05).Among patients in the esophageal surgery group,the age of HAI group was higher than that of the non-HAI group(P＜0.05).Higher RW score level was associated with higher incidence of HAI(P＜0.05).Among patients in the mediastinum sur-gery group,the age of patients in the infected group was higher than that in the non-infected group(P＜0.05).Among the 59 HAI cases,31 were infected with MDROs.Conclusion Focusing on CMI and RW in the DRGs in-dex system,analyzing HAI from the perspectives of disease complexity and overall technical difficulties of medical services can provide reference for the precise management of HAI in the new era.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam^®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R² = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f₁ and similarity factor f₂ were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.

As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective:To investigate the mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation by predicting targets and signaling pathways based on network pharmacology.Method:The traditional Chinese medicine system platform (TCMSP) database was used to screen out active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma,predict targets,and construct the active component-predicted target network.Through the Online Mendelian Inheritance in Man (OMIM),Therapeutic Target Database (TTD),and Genecards databases,potential target information of atrial fibrillation was retrieved.STRING 11.0 database was used to obtain the protein-protein interaction data of relevant targets,and the results were visualized by Cytoscape 3.7.1 software to construct protein-protein interaction network relating to atrial fibrillation.The predicted targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were mapped to the potential targets of atrial fibrillation.The intersection targets were the potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma.Then,Visualization and Integrated Discovery (DAVID),a database for annotation,was used to analyze biological functions and pathways of the potential targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in the treatment of atrial fibrillation.Finally,Cytoscape3.7.1 software was utilized to construct active component-potential target-signal pathway network of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation.Result:Totally 51 active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were screened out,and 18 potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were predicted.The effect was mainly correlated with the regulation of interleukin-6 (IL-6),sodium channel protein type 5 subunit alpha (SCN5A),tumor necrosis factor (TNF),nitric-oxide synthase,endothelial (NOS3),potassium voltage-gated channel subfamily hmember 2 (KCNH2),collagen alpha-1(I) chain (COL1A1),retinoic acid receptor RXR-alpha (RXRA),tissue factor (F3),alpha-1B adrenergic receptor (ADRA1B) and other target proteins,cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase G (PKG) signaling pathway,phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt) signaling pathway,transcriptional disorders in cancer,calcium signaling pathways,and adrenergic signals in cardiomyocytes.Conclusion:Nardostachyos Radix et Rhizoma and Corydalis Rhizoma treat atrial fibrillation based on multiple components,multiple targets and multiple channels,and provide a scientific basis for subsequent experimental studies for further explainning its mechanism of action.