Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To study the impact of different scattering correction algorithms in the reconstruction of PET/CT images on image artifacts and the precision of quantitative parameters.Methods:The phantom as described in the National Electrical Manufacturers Association (NEMA) NU2 standard was filled with 18F. The background activity was fixed, and the activity of the solution in the spheres was adjusted to obtain several configurations, including the normal ratio group (4.08∶1) and the extreme ratio group (200∶1). The surface contamination group with the same ratio as the extreme ratio group contained a small radioactive source with different doses of 18F (74, 37, 3.7 and 0.37 MBq) placed at the surface of the phantom. PET/CT images of 30 patients (21 males, 9 females, age: (44.5±10.2) years) from Peking University Cancer Hospital & Institute between July 2012 and December 2021 were retrospectively analyzed, including 10 with normal images ( 18F-FDG) and 20 with abnormal images (10 with dislocation during acquisition, 10 with surface contamination). The images were reconstructed with relative and absolute scattering correction. The phantom was evaluated using the target to background ratio (TBR) and the artifact classification. CV as well as the artifact classification were used to compare the clinical image quality. Mann-Whitney U test and χ2 test were used to analyze data. Results:In the normal ratio group and the extreme ratio group, the TBRs of phantom images reconstructed with relative correction were significantly higher than those with absolute correction (normal ratio group: 3.30(1.94, 4.53) vs 2.72(1.56, 3.56); z=-2.20, P=0.028; extreme ratio group: 105.47(45.62, 162.82) vs 101.36(43.96, 155.57); z=-1.99, P=0.046). In the surface contamination group, with the increase of the activity of the small source, the artifact became more obvious, and the artifact classification score of absolute correction was significantly better than that of relative correction (1.5(1.0, 2.0) vs 2.5(2.0, 3.0); z=-2.00, P=0.046). In the 10 normal 18F-FDG PET/CT patients, the CVliver of the relative correction (9.67%(8.00%, 11.00%)) was significantly lower than that of absolute correction (11.00%(9.00%, 12.00%); z=-2.57, P=0.010), indicating the higher image quality of images with relative correction. In abnormal images, the image quality of absolute correction was significantly higher than that of relative correction with fewer and less severe artifacts (dislocation cases: 9/10 vs 4/10; χ2=5.50, P=0.019; surface contamination cases: 9/10 vs 4/10; χ2=5.50, P=0.019). Conclusions:The relative scattering correction is suitable for normal situations in clinical PET acquisition. However, with dislocation or surface contamination, the absolute scattering correction helps to reduce the artifacts and improve the image quality.

Objective: To analyze the differences between adults and children in the epidemic characteristics and clinical manifestations of chickenpox and provide a reference for the prevention strategy adjustment of chickenpox. Methods: The incidence data of chickenpox surveillance in Shandong Province from January 2019 to December 2021 were collected. Descriptive epidemiological methods were used to analyze the distribution of cases, and the chi-square test was used to compare the differences in epidemiological characteristics and clinical manifestations of varicella cases between adults and children. Results: A total of 66 182 cases of chickenpox were reported from 2019 to 2021, including 24 085 cases of adults chickenpox, the male to female sex ratio was 1∶1 (12 032∶12 053), basically the same for men and women, and 42 097 cases of children chickenpox, with a gender ratio of 1.4∶1, the male to female ratio was 1.4∶1 (24 699∶17 398). Fever in chickenpox cases was mainly low and moderate, but the proportion of moderate fever with temperature between 38.1 and 39.0 ℃ in children cases (35.0%,14 744/42 097) was significantly higher than that in adults (32.0%,7 696/24 085). The number of herpes in chickenpox cases was mainly less than 50, but the proportion of severe cases with 100-200 herpes in children was higher than that in adults. The incidence rate of complications was 1.4% (333/24 085) in adults chickenpox, the incidence rate of complications was 1.7% (731/42 097) in children chickenpox. The incidence of encephalitis and pneumonia in children was higher than in adults, and the difference was statistically significant (P<0.05). The proportion of chickenpox cases was mainly outpatient, but the hospitalization rate of children cases was 14.4% (6 049/42 097), higher than that of adults, which was 10.7% (2 585/24 085). Conclusions: There were differences between adult chickenpox and child chickenpox in terms of epidemic and clinical manifestations; the symptoms of child chickenpox were more serious than adult chickenpox. However, the adult chickenpox population is generally susceptible and lacks immune strategy protection, which calls for more attention.
Child ; Humans ; Adult ; Male ; Female ; Infant ; Chickenpox/prevention & control* ; Hospitalization ; Incidence ; Pneumonia/epidemiology* ; Epidemics ; Fever/epidemiology* ; Chickenpox Vaccine

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D_(eff)) and activation energy(E_a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D_(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E_a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.
Atractylodes ; Drugs, Chinese Herbal ; Hot Temperature ; Kinetics ; Rhizome

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies