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

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective:To study the position of computed tomography(CT)slice of marker points of radiotherapy,which was determined by control scan(CS)method,on the application effect of patients with head and neck tumors who received radiotherapy.Methods:Based on Control Scan(CS)method,a calculator program of mark-point slice position was made,which was an enterprise WeChat program that could be used in calculating position and CT position scan of patients with head and neck tumor(slice thickness was 3mm).A total of 60 patients with head and neck tumor were selected,and the patients who underwent CT positioning scan by using CS method were divided into observation group,and patients who underwent CT position scan by using conventional method were divided into control group,with 30 cases in each group.The number of cases with three metal marker points displayed at the same slice,and the number of slices containing the CT images of marker point between the located CT scan were compared.Results:The number of patients in the observation group and the control group who showed three markers at the same level at the same time were respectively 26 cases and 13 cases,and observation group increased by 13 cases(43.4%)than control group,and the difference was significant(x2=12.382,P<0.05).The number of CT images with only 1 slice of observation group and control group were respectively 4 cases and 0 cases,which increased by 4 cases(13.3%)than the control group,and the difference was significant(x2=2.411,P<0.05).Conclusions:The CT localization scan of radiotherapy,which uses CS to assist patients with head and neck tumor,can precisely calculate and obtain the primary position of target of CT localization scan.It can take the images of 3 mental marker points of patient who receives radiotherapy to occur at the same CT slice as soon as possible,which has better application effect.It can effectively improve the convenience and work effectiveness of radiotherapy.

Objective:To evaluate the effect of neck muscle training on reducing the neck setup error during radiotherapy in patients with nasopharyngeal carcinoma.Methods:Clinical data of nasopharyngeal carcinoma patients who were treated with radiotherapy in the First Affiliated Hospital of Air Force Medical University from February 2021 to October 2022 were selected and analyzed. All subjects were randomly divided into the experimental group ( n=48) and control group ( n=51) at a ratio of 1:1 using a random number table method. In the experimental group, patients received neck muscle training prior to treatment, and those in the control group received conventional treatment without additional interventions. Cone beam computed tomography (CBCT) was performed weekly to measure and analyze the setup errors at the level of the slopes, 4th cervical vertebra (C4) and 7th cervical vertebra (C7). The four-dimensional displacement [left-right (LR), superior-inferior (SI), anterior-posterior (AP), rotation (Rtn)] systematic errors and random errors at each level were calculated, and the planning target volume (PTV) boundary was calculated. The differences at three different levels of slope, C4, C7 (LR, SI, AP axis) were compared between two groups. The correlation of setup errors in each direction was analyzed by Spearman correlation analysis. The changes of cervical curvature, cutaneous toxicity (common terminology criteria for adverse events V3.0) and pain assessment (numerical rating scale) were compared between two groups. Qualitative data between two groups were compared by χ2 test. Quantitative data between two groups were compared by t-test. Results:Baseline features were well balanced in both groups. The setup error in the experimental group was smaller than that in the control group. For the setup error in the AP direction, the setup errors at the levels of slope, C4 and C7 in the experimental group were (0.94±0.88) mm, (1.13±1.03) mm and (1.32±1.22) mm, significantly less than (1.66±1.23) mm, (1.63±1.35) mm and (1.89±1.48) mm in the control group (all P<0.001). In the SI direction, the setup errors at the levels of slope, C4 and C7 in the experimental group were (1.14±0.87) mm, (1.31±0.93) mm and (1.39±0.95) mm, compared with (1.22±0.95) mm, (1.40±1.11) mm and (1.52±1.08) mm in the control group ( P=0.278, 0.272, 0.100). The differences in the AP direction at the level of C4 and C7 in the experimental group were smaller than those in the control group ( P=0.014, 0.005). The required PTV boundary in the AP direction in the experimental group was increased from 1.77 mm at the slope level to 2.98 mm at the level of C7. In the control group, it was increased from 3.02 mm at the slope level to 4.78 mm at the level of C7. Correlation analysis showed that at the C4 and C7 levels, and the setup errors in the SI direction were moderately negatively correlated with those in the AR direction. There were no significant differences in cervical curvature, skin toxicity and pain assessment between two groups. Conclusion:Neck muscle training can reduce the setup error in the AP direction and PTV boundary of radiotherapy in patients with nasopharyngeal carcinoma, which is worthy of clinical promotion.

Objective:To investigate the role of cervical core muscle group exercise and massage in the change of cervical spine curvature during radiotherapy for head and neck tumors and the effect on set-up errors.Methods:A total of 40 patients with head and neck tumours receiving radiotherapy in the First Affiliated Hospital of Air Force Military Medical University from March 2020 to July 2021 were prospectively selected, and all of them underwent different degrees of changes in cervical spine curvature during radiotherapy. The cervical core muscle exercise and manual massage were used to do treatment intervention on the change in the cervical spine curvature. Changes in cervical spine curvature at the time of the curvature change of the cervical spine and at 1 d, 3 d and 5 d after the intervention were observed by using cone beam CT, and then data were recorded in 3 dimensions. The set-up error when cervical spine curvature changed was compared with that after the muscle group exercise and manipulation, and Pearson was used to analyze the linear correlation of set-up errors in each direction.Results:There were 23 males and 17 females, with a median age of 41 years (26-62 years). The significant improvement of cervical curvature at 1 d, 3 d and 5 d after the intervention could be found in 2 cases (5.0%), 20 cases (50.0%) and 39 cases (97.5%). Using the cervical 4 vertebrae as the matching standard, the set-up errors at the time of change in cervical spine curvature and at 1 d, 3 d and 5 d after treatment were (1.3±0.9) mm, (1.2±0.8) mm, (1.3±0.7) mm and (1.3±0.7) mm in the left-right direction respectively; (2.0±0.7) mm, (1.7±0.8) mm, (1.8±0.7) mm and (1.9±0.8) mm in the head-foot direction respectively; (4.9±0.7) mm, (4.6±0.7) mm, (3.4±0.7) mm, (1.7±0.6) mm in the anterior-posterior direction respectively. The set-up error in the anterior-posterior directions at 3 d and 5 d after treatment intervention was lower than that at the time of change in cervical spine curvature and at 1 d after treatment intervention (all P < 0.01), and that at 5 d after treatment intervention was lower than that at 3 d after treatment intervention ( P < 0.01). There were no statistically significant differences between the left-right direction and head-foot direction at each time point (all P > 0.05). There was no correlation between left-right direction and head-foot direction ( r = 0.049, P = 0.540), between left-right direction and anterior-posterior direction ( r = 0.041, P = 0.607), and between head-foot direction and anterior-posterior direction ( r = 0.003, P = 0.931) in terms of set-up errors. Conclusions:Core cervical muscle group training and massage could improve the change in cervical spine curvature, increase the repeatability of the set-up, which provides a favourable guarantee for accurate treatment.

Objective:To evaluate the predictive value of age-adjusted Charlson comorbidity index (ACCI) for in-hospital mortality and 1-year mortality in patients with acute type A aortic dissection (ATAAD).Methods:This was a retrospective cohort study, and the clinical data of ATAAD patients admitted to Wuhan Union Hospital from January 1, 1999 to December 31, 2018 were collected for analysis. All the patients were confirmed by computed tomography angiography or magnetic resonance imaging of the aorta and the onset time was less than 14 days. Patients who survived at discharge were followed up to obtain 1-year survival information. The ACCI score was calculated for patients based on their comorbidities and age at admission, and they were divided into three groups of 0, 1 and ≥2 according to the ACCI score. The in-hospital mortality and 1-year mortality of the three groups were compared. Logistic regression analysis was applied to determine the independent predictors for in-hospital mortality and 1-year mortality.Results:Among 1 133 ATAAD patients, 383, 357 and 393 patients had ACCI score of 0, 1, and ≥2, respectively. The in-hospital mortality and 1-year mortality of patients with ACCI score ≥2 were significantly higher than those of patients with ACCI score of 0 (25.4% vs. 17.0%, 30.0% vs. 19.6%, both P<0.05). Multivariate Logistic regression analysis showed that ACCI score ≥2 was an independent risk factor for in-hospital mortality ( OR=1.670, 95% CI: 1.176-2.370, P=0.004) and 1-year mortality ( OR=1.762, 95% CI: 1.264-2.456, P<0.001). Age (per 10-year increase) and cerebrovascular diseases were independent risk factors for in-hospital mortality and 1-year mortality, while diabetes mellitus was a protective factor for in-hospital mortality. Conclusions:ACCI can predict the in-hospital mortality and 1-year mortality of ATAAD patients, and patients with ACCI score ≥2 have a poorer prognosis.

Objective:To explore the changes of hip joint function in patients with total hip arthroplasty (THA) within three months after operation, and to explore the impact of fear of falling on hip joint function recovery.Methods:From December 2020 to August 2021, 205 patients with THA after operation in the Xinjiang Uygur Municipal People's Hospital were selected as the study subject by objective sampling. The patients were investigated with the General Information Questionnaire, the Chinese version of Falls Efficacy Scale-International (FES-I) , and the Harris Hip Score after the first activity out of bed, one month and three months after operation. Pearson correlation was used to analyze the correlation between the scores of FES-I in Chinese version and the scores of Harris Hip Score in different periods after operation, and multiple linear regression were used to analyze the influencing factors of hip joint function recovery in different periods after operation.Results:After the first activity out of bed, one month and three months after operation, the FES-I scores of 205 patients after THA were (32.24±6.05) , (30.94±6.04) and (28.48±3.52) respectively, and the scores of Harris Hip Score were (61.49±8.92) , (72.58±5.52) and (89.15±5.70) respectively, and the correlation analysis showed that they were negatively correlated ( r=-0.512, -0.523, -0.549; P<0.05) . The results of multiple linear regression analysis showed that age and fear of falling were the influencing factors for the hip joint function recovery when THA patients got out of bed for the first time after operation ( P<0.05) , which could explain 31.2% of the total variation. Sex, age, number of concomitant diseases and fear of falling were the influencing factors of hip joint function recovery in THA patients one month after operation ( P<0.05) , which could explain 43.7% of the total variation. Sex, age, number of concomitant diseases and fear of falling were the influencing factors of hip joint function recovery in THA patients three months after operation ( P<0.05) , which could explain 36.9% of the total variation. Conclusions:The recovery of hip joint function in THA patients shows an overall upward trend three months after operation. The impact of fear of falling on the recovery of hip joint function in different periods persists. The higher the level of fear of falling, the worse the recovery of hip joint function. Nurses should evaluate the patients' fear of falling at different periods after operation, and strengthen the attention and guidance to patients with high fear of falling, elderly patients, and patients with other diseases, so as to promote the recovery of patients' joint function.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Objective : To investigate the serum levels of antibodies against SARS-CoV-2 after inoculation of an inactivated SARS-CoV-2 vaccine, so as to provide insights into the evaluation of the vaccine immunogenicity. Methods : In this single-arm Objective performance criteria trial, residents aged 18 to 59 years and inoculated with an inactivated SARS-CoV-2 vaccine in Xihu District, Hangzhou City from October to December of 2020 were selected using a cluster sampling method. Blood samples were collected prior to inoculation, 14 and 28 days post-inoculation of the first dose, and 28 days post-inoculation of the second dose. Serum levels of anti-SARS-CoV-2 IgM and IgG antibodies were detected using the magnetic particle-based chemiluminescence immunoassay. The seroconversion of antibodies and dynamic changes of antibody levels were analyzed. Results : Totally 310 participants were enrolled, including 133 subjects on day 14 post-inoculation of the first dose, 97 subjects on day 28 post-inoculation of the first dose and 254 subjects on day 28 post-inoculation of the second dose. The seroconversion rates of anti-SARS-CoV-2 IgG antibody were 6.02%, 28.87% and 98.43%, and the median IgG antibody levels were 1.76 ( interquartile range, 3.25 ), 5.69 ( 9.95 ) and 52.05 ( 47.60 ) AU/mL ( P<0.05 ), respectively, while the seroconversion rates of anti-SARS-CoV-2 IgM antibody were 9.02%, 11.34% and 12.99%, and the median IgG antibody levels were 1.89 ( 3.28 ), 2.06 ( 4.71 ) and 2.65 ( 4.01 ) AU/mL ( P>0.05 ), respectively. In addition, higher serum levels of anti-SARS-CoV-2 IgG and IgM antibodies were detected post-inoculation relative to pre-inoculation ( P<0.05 ), and higher serum IgG antibody levels were found in subjects aged 18 to 39 years than in those aged 40 to 59 years ( P<0.05 ). Conclusions Inoculation of two doses of the inactivated SARS-CoV-2 vaccine achieves a high immunogenicity among residents aged 18 to 59 years 28 days post-inoculation, and the anti-SARS-CoV-2 IgM antibody is detectable in some residents following inoculation of the first dose.

Objective:To investigate the influence of hypomagnesemia on the prognosis of patients with severe sepsis.Methods:A retrospective study was conducted. The clinical data of 207 septic patients admitted to the department of critical care medicine of the First Affiliated Hospital of University of Science and Technology of China from January 1, 2016 to December 21, 2020 were analyzed, including gender, age and laboratory indicators within 24 hours after sepsis diagnosis [procalcitonin (PCT), C-reactive protein (CRP), blood lactic acid (Lac), pH value and blood magnesium, calcium, chlorine and phosphorus levels]. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score and 28-day prognosis were collected. The patients were divided into survival group and non-survival group according to the prognosis, and the clinical data and laboratory indexes were compared between the two groups. Pearson correlation test was used to analyze the correlation between clinical indicators. Multivariate Logistic regression analysis was used to screen the risk factors affecting the prognosis. The receiver operator characteristic curve (ROC curve) was drawn, and the area under ROC curve (AUC) was calculated to evaluate the potential prognostic indicators.Results:Among the 207 septic patients, 102 survived and 105 died on the 28th day, and the 28-day mortality was 50.72%. There were no significant differences in gender, age, CRP, pH value, blood chlorine or blood phosphorus levels between the two groups. The blood magnesium and blood calcium levels in the non-survival group were significantly lower than those in the survival group [blood magnesium (mmol/L): 0.68±0.14 vs. 0.80±0.12, blood calcium (mmol/L): 1.93±0.21 vs. 2.01±0.20, both P < 0.01], and PCT, Lac, APACHE Ⅱ score and SOFA score were significantly higher than those in the survival group [PCT (mg/L): 8.32 (1.64, 55.01) vs. 3.55 (0.97, 12.31), Lac (mmol/L): 2.90 (1.70, 4.30) vs. 2.10 (1.03, 3.89), APACHE Ⅱ score: 21.24±6.40 vs. 17.42±7.02, SOFA score: 9.14±3.55 vs. 6.91±3.31, all P < 0.01]. Among the 207 patients, 96 patients had normal blood magnesium level (0.75-1.25 mmol/L) and 111 patients had hypomagnesemia (< 0.75 mmol/L). The 28-day mortality of septic patients in the hypomagnesemia group was significantly higher than that in the normal magnesium group [61.26% (68/111) vs. 38.54% (37/96), P < 0.01]. Pearson correlation analysis showed that the blood magnesium level of sepsis patients was negatively correlated with PCT ( r = -0.173, P < 0.05), and it was positively correlated with APACHE Ⅱ score ( r = 0.159, P < 0.05), but it had no correlation with CRP or SOFA score ( r values were -0.029 and 0.091, both P > 0.05). Logistic regression analysis showed that serum magnesium, APACHE Ⅱ score and SOFA score were independent risk factors for 28-day death in patients with sepsis [serum magnesium: odds ratio ( OR) < 0.001, 95% confidence interval (95% CI) was 0.000-0.002, P < 0.001; APACHE Ⅱ score: OR = 1.092, 95% CI was 1.022-1.168, P = 0.010; SOFA score: OR = 1.168, 95% CI was 1.026-1.330, P = 0.019]. ROC curve analysis showed that blood magnesium and APACHE Ⅱ score had a certain predictive value for 28-day mortality in patients with severe sepsis [AUC (95% CI) was 0.723 (0.655-0.791) and 0.680 (0.607-0.754), respectively]. When the blood magnesium threshold was 0.64 mmol/L, the sensitivity was 41.0% and the specificity was 93.1%. When APACHE Ⅱ score threshold was 16.50, the sensitivity was 78.1% and the specificity was 55.9% indicating that the specificity of serum magnesium was higher than that of APACHE Ⅱ score. Conclusions:Severe septic patients complicated with hypomagnesemia have a poor prognosis. Serum magnesium level can be used as a prognostic indicator for severe septic patients.