Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human models in biomedical research. In response to this demand, organoids and organ chips were integrated for greater physiological relevance and dynamic, controlled experimental conditions. This innovative platform-the organoids-on-a-chip technology-shows great promise in disease modeling, drug discovery, and personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, and industry stakeholders. This review traces the evolution from organoids to organoids-on-a-chip, driven by the necessity for advanced biological models. We summarize the applications of organoids-on-a-chip in simulating physiological and pathological phenotypes and therapeutic evaluation of this technology. This section highlights how integrating technologies from organ chips, such as microfluidic systems, mechanical stimulation, and sensor integration, optimizes organoid cell types, spatial structure, and physiological functions, thereby expanding their biomedical applications. We conclude by addressing the current challenges in the development of organoids-on-a-chip and offering insights into the prospects. The advancement of organoids-on-a-chip is poised to enhance fidelity, standardization, and scalability. Furthermore, the integration of cutting-edge technologies and interdisciplinary collaborations will be crucial for the progression of organoids-on-a-chip technology.
Organoids/physiology* ; Humans ; Biomedical Research/methods* ; Lab-On-A-Chip Devices ; Animals ; Microphysiological Systems

OBJECTIVE To explore the in vitro and in vivo inhibitory effects and mechanism of metformin on the malignant biological behavior of esophageal squamous cell carcinoma （ESCC） cells by the hypoxia inducible factor-1α （HIF-1α）/interleukin-8 （IL-8） signaling pathway. METHODS Human ESCC TE1 cells were assigned into blank group， metformin low-， medium-， and high-dose groups （0.5， 1， 2 mmol/L）， IDF-11774 （HIF-1α inhibitor） group （20 μmol/L）， and high-dose metformin+HIF-1α activator dimethyloxalylglycine （DMOG） group. After 24 h treatment， cell proliferation [measured by the positive rate of 5-ethynyl- 2′-deoxyuridine （EdU） and optical density at 450 nm （OD450 value）]， apoptosis， invasion and migration as well as mRNA expressions of proliferating cell nuclear antigen （PCNA）， Bcl-2 interacting mediator of cell death （Bim）， migration and invasion enhancer 1 （MIEN1）， and matrix metalloproteinase-9 （MMP-9）， and protein expressions of HIF-1α and IL-8 in the cells were detected. The xenograft tumor model of nude mice was established. Thirty nude mice were randomly divided into blank group， metformin low-， medium-， and high-dose groups （i.g. administration of metformin 62.5， 125， 250 mg/kg+i.p. administration of equal volume of normal saline）， IDF-11774 group （i.g. administration of 50 mg/kg IDF-11774+i.p. administration of equal volume of normal saline） and high-dose metformin+DMOG group （i.g. administration of metformin 250 mg/kg+i.p. administration of DMOG 250 mg/kg）， with 5 mice in each group. They were given relevant medicine， once a day， for 4 consecutive weeks； the mass and volume of the tumor and protein expressions of HIF-1α and IL-8 in the tumor tissue were determined. RESULTS The EdU positive rate， OD450 value， cell invasion number， scratch healing rate， mRNA expressions of PCNA， MIEN1 and MMP-9， protein expressions of HIF-1α and IL-8， as well as the mass and volume of transplanted tumors and protein expressions of HIF-1α and IL-8 in tumor tissues were decreased by metformin in concentration/dose-dependent manner （P＜0.05）. Additionally，metformin increased the apoptosis rate and mRNA expression of Bim in cells （P＜0.05）. The trend of changes in corresponding indicators in the IDF-11774 group was consistent with that in the metformin groups， whereas DMOG could significantly attenuate the aforementioned effects of high-concentration/high-dose metformin （P＜0.05）. CONCLUSIONS Metformin can inhibit the proliferation， invasion， migration of TE1 cells， and tumor growth of nude mice， and induce cell apoptosis， the mechanism of which may be related to the inhibition of HIF-1α/IL-8 signaling pathway.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

Objective To analyze the diagnostic value of fat content measurement based on magnetic resonance multi-echo Dixon(ME-Dixon)technique combined with serological indicators for early liver fibrosis.Methods A total of 78 patients with early liver fibrosis who underwent liver biopsy at the First Affiliated Hospital of Army Medical University from August 2019 to October 2021 were included.According to the pathological results,the patients with early liver fibrosis were divided into the S0 group(n=21),the S1 group(n=32),and the S2 group(n=25).Meanwhile,the complete imaging examination results(including ME-Dixon sequence)and laboratory examination results[including hyaluronic acid(HA),procollagen Ⅲ(PCⅢ),collagen Ⅳ(CⅣ),laminin(LN),aspartate transaminase(AST),alanine amino-transferase(ALT),gamma-glutamyl transferase(GGT),alkaline phosphatase(ALP)]were collected.And the hepatic fat fraction(HFF)was measured by ME-Dixon technique.One-way ANOVA was used to analyze the differences in HFF and serological indicators among the three groups,and then factors with statistical differences in the univariate analysis were selected to draw receiver operating characteristic(ROC)curve,and the area under the curve(AUC)was calculated to evaluate their value in the diagnosis of liver fibrosis and the degree of early liver fibrosis.Results There was no statistically significant difference in the PCⅢ,LN,AST,or ALT among the S0,S1,and S2 groups(P>0.05),while there were statistically significant differences in the HFF,HA,CⅣ,GGT,and ALP(P<0.05),and the levels of HA,CⅣ,GGT,and ALP in the S2 group were significantly higher than those in the S0 and S1 groups(P<0.05).ROC curve analysis showed that the above indicators for diagnosing liver fibrosis and the degree of early liver fibrosis based on AUC values were in the following order:HFF+GGT(0.72)>HFF(0.68)>GGT(0.61)>CⅣ(0.54)>ALP(0.53)>HA(0.48)and HA+CⅣ(0.71)>CⅣ(0.68)>HA(0.66)>GGT(0.61)>ALP(0.59)>HFF(0.46).Conclusion The fat content measurement based on magnetic resonance ME-Dixon tech-nique combined with serological indicators has significant reference value for the diagnosis of early liver fibrosis,and it plays a certain guid-ing role in clinical diagnosis and treatment.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.