BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Surgery combined with postoperative stereotactic radiosurgery (SRS) can improve the overall survival and becomes one of main treatments for resectable brain metastases. Compared with postoperative SRS, preoperative SRS (Pre-SRS) has theoretical advantages of reducing the dissemination of active tumor cells into the treatment cavity during surgery, reducing radiation dose, reducing radiation to surrounding normal brain tissue, and ensuring successful implementation of perioperative treatment, etc. Recent clinical studies have confirmed that Pre-SRS can reduce local recurrence rate and the incidence of radiation necrosis (RN) and leptomeningeal metastasis (LMM). Moreover, the indications, dose fractionation, and combined therapy remain to be confirmed by more prospective studies. In this article, research progress in Pre-SRS for resectable brain metastases was reviewed.

Objective:To explore the diagnostic value of color Doppler ultrasonography for transplanted pancreatic venous thrombosis after simultaneous pancreas-kidney transplantation(SPK).Methods:From June 2019 to September 2022, retrospective analysis was conducted for the relevant clinical data of 181 recipients of SPK.Based upon a presence or absence of clinical high-risk factors, such as a sudden decline of blood/urine amylase, elevated fasting blood glucose and D-dimer, they were assigned into two groups of high-risk(n=48)and non-high-risk(n=133). Color Doppler ultrasonography was performed for evaluating the status of transplanted pancreas and reconstructed blood vessels and diagnosing pancreatic thrombosis post-SPK.Also they were divided into two groups of donor splenic vein thrombosis(n=6)and non-thrombosis(n=39)based upon the presence or absence of splenic vein thrombosis.Various laboratory parameters(fasting blood glucose, blood/urine amylase, fatty acids & D-dimer)and transplanted pancreatic ultrasonic measurements(thickness of transplanted pancreatic head/body/tail, inner diameter & blood flow velocity of donor splenic vein, transplanted pancreatic parenchymal arterial blood flow velocity and resistance index)were recorded.Measurement data were tested for normal distribution and homogeneity of variances.Group comparisons for measurement data fulfilling the criteria of normal distribution and homogeneity of variances were conducted by t-test.For data not fulfilling these criteria, Mann-Whitney U test was utilized.Results:Among 9 cases of pancreatic thrombosis as diagnosed by color Doppler ultrasonography, pancreatic venous thrombosis(n=6)occurred in donor splenic vein.The proportion of transplanted pancreatic thrombosis occurring within Week 2 was 88.9%(8/9)and the proportion of transplanted pancreatic venous thrombosis occurring within Week 2 3.3%(5/6). Fasting blood glucose, blood amylase, urine amylase and D-dimer of high-risk group were(14.7±1.9)U/L, (92.6±15.4)mmol/L, (9.7±1.7)U/L and(6.1±2.2)mg/L.The corresponding values for non-high-risk group were(4.9±0.6)U/L, (209.4±34.4)mmol/L, (168.2±95.7)U/L and(1.3±0.6)mg/L respectively.Statistically significant inter-group differences existed( P=0.021, 0.035, 0.001, 0.017). Pancreatic thrombosis was diagnosed by color Doppler ultrasonography in 9 patients in high-risk group and 8 cases occurred within Week 2 post-SPK.Among 6 cases of pancreatic venous thrombosis, 5 cases occurred in donor splenic veins within Week 2 post-SPK.No significant differences existed in the above parameters between group with donor splenic vein thrombosis and group without donor splenic vein thrombosis( P>0.05). Inner diameters of splenic veins in groups with and without splenic vein thrombosis were(11.7±0.5)and(3.9±0.2)mm.Blood flow velocities in splenic veins were(18.3±8.4)and(40.3±16.6)cm/s respectively.The inter-group differences were statistically significant( P=0.001, 0.006). No significant differences existed in thickness of transplanted pancreatic head/body/tail, as well as blood flow velocity or resistance index in transplant pancreatic artery( P>0.05). Conclusions:Fasting blood glucose, blood amylase, urine amylase, fatty acid and D-dimer are important and yet non-specific biochemical parameters in the diagnosis of pancreatic transplantation thrombosis.Color Doppler ultrasonography may provide valuable imaging diagnostic rationales for making an early diagnosis and providing timely interventions of transplanted pancreatic venous thrombosis post-SPK.It is imperative to enhance dynamic monitoring using color Doppler ultrasound within 1-2 weeks post-SPK.Greater attention should be paid to internal diameter and blood flow velocity of donor splenic vein.

Ureteral stricture in renal allografts is one of the common postoperative complications in kidney transplant recipients. Due to short ureter in renal allografts, endovascular treatment should be adopted before reconstruction surgery to avoid irreversible injury. Alleviating renal allograft injury, easing obstruction or establishing drainage channel are the key measures to treat ureteral stricture. In endovascular treatment, balloon dilatation and internal incision yield high recurrence rate, and long-term indwelling of self-expanding metallic ureteral stents may be a better option. Compared with traditional stents, metallic stents may maintain urinary tract patency for a long time and mitigate the irritation of lower urinary tract symptoms,with different indications and efficacy. Although all metallic stents may be displaced and occluded, it still plays a positive role in the treatment of ureteral stricture in renal allografts. In this article, the application of self-expanding metallic ureteral stent in ureteral stricture of renal allografts was mainly illustrated, aiming to provide reference for optimizing the treatment of ureteral stricture in renal allografts.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Objective:To study the effect of heated carbon dioxide pneumoperitoneum on the prognosis of patients undergoing pancreaticoduodenectomy by Da Vinci robot.Methods:A total of 307 patients who underwent pancreaticoduodenectomy by Da Vinci robot from January 2016 to December 2018 were selected as subjects. 140 patients who underwent pancreaticoduodenectomy from January 2016 to April 2017 were selected as the control group, and room temperature carbon dioxide pneumoperitoneum was used. From May 2017 to December 2018, 167 patients were set as the intervention group, and heated carbon dioxide pneumoperitoneum was used. Body temperature, heart rate and blood oxygen saturation of the two groups were compared after entering the operating room, before anesthesia, before the establishment of carbon dioxide pneumoperitoneum and after the closure of carbon dioxide pneumoperitoneum, and the duration of operation, intraoperative blood loss, postoperative anesthesia recovery time, hospitalization time and postoperative complication rate were recorded.Results:There was no significant difference in body temperature after entering the operating room, before the establishment of carbon dioxide pneumoperitoneum between the two groups ( P>0.05). After the closure of carbon dioxide pneumoperitoneum, the decline range of the body temperature of the control group was(1.24±2.36) ℃, which was significantly higher than that of the intervention group (0.60±0.25) ℃, and the difference was statistically significant ( t value was 6.892, P<0.05). There were no statistically significant differences between the two groups in terms of operation duration, number of cases with blood oxygen saturation < 0.90, incidence of gastrointestinal fistula and incision infection ( P>0.05). The intraoperative blood loss, resuscitation time, drainage time was (291.08±265.42) ml, (27.04±10.89) min, (8.69±6.64) d in the intervention group and (364.29±309.28) ml, (32.60±12.17) min, (10.76±6.25) d in the control group, and the difference was statistically significant ( t value was 2.232, 7.294, 2.789, P<0.05 or 0.01). There was statistically significant difference in The incidence of pancreatic fistula and biliary fistula, and length of hospital stay was 20 cases, 7 cases, (27.62±17.30) d in the intervention group, and 31 cases, 15 cases, (32.38±12.22) d in the control group, and the difference was statistically significant ( χ2 value was 4.653, 4.870, t value was 6.284, P<0.05). Conclusions:Warming carbon dioxide pneumoperitoneum can reduce the incidence of perioperative hypothermia and improve the prognosis of patients undergoing pancreaticoduodenectomy by Da Vinci robot.

Objective:To observe the changing characteristics of pharmacokinetic and pharmacodynamic (PK-PD) parameters of vancomycin in critical patients under different drug regimens and to further explore the influencing factors.Methods:The clinical data of patients who treated with vancomycin and recorded by steady-state through concentration (C min) admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to December 2018 were analyzed retrospectively. The patients were divided into three groups according to the dosing interval (groups of q12 h, q8 h and q6 h respectively) and C min was collected. The serum concentration of vancomycin before (0 hour) and 1, 2, 4, 6, 8, 12 and 24 hours after administration were estimated by JPKD Ver 3.1. Area under the curve (AUC 0-24 h) was estimated by trapezoidal area method. Minimum inhibitory concentration (MIC) of pathogenic microorganisms in the same period was retrieved, thus AUC 0-24 h/MIC was calculated. Results:285 patients with 529 records of C min were enrolled in the study, including 375 data in q12 h group, 121 data in q8 h group and 33 data in q6 h group. After unifying daily dose by JPKD Ver 3.1, the C min (10-20 mg/L) reaching rate of q12 h group, q8 h group, q6 h group were 35.7%, 43.8% and 60.6%, respectively, while only q12 h group was statistically significant compared with q6 h group ( P < 0.01). q6 h group and q8 h group showed higher C min than q12 h group (mg/L: 13.8±5.2, 13.5±7.3 vs. 11.4±7.9, both P < 0.05) and lower peak concentration (C max) than q12 h group (mg/L: 19.4±5.3, 21.5±7.3 vs. 23.9±8.1, both P < 0.05). However, there was no significant difference in terms of percentage of PD target (AUC 0-24 h/MIC≥400) among the three groups (q12 h group, q8 h group, q6 h group were 38.1%, 41.3%, 45.5%, P > 0.05). Multiple linear regression analysis showed that creatinine clearance (CCr) and vancomycin clearance (CLvancomycin) were the main influencing factors of vancomycin PD parameters such as C min and AUC 0-24 h/MIC ( r values of CCr were -0.391, -0.424, and rvalues of CLvancomycin were -0.673, -0.663, all P < 0.01), and were negatively correlated with age ( r values were -0.432 and -0.488, respectively, both P < 0.01). Conclusions:At the same daily dose, C min can be increased and C max can be decreased by increasing the frequency of vancomycin administration, thus minimize the fluctuation of vancomycin serum concentration, but AUC 0-24 h/MIC is not affected. Vancomycin administration regimen in severe patients should be optimized according to CCr, CLvancomycin and age.

Objective:To construct an evaluation index system of nursing quality for pressure injury in Operating Room based on Donabedian structure-process-outcome three-dimensional quality assessment model to provide a reference for nursing quality assessment by nursing managers in Operating Room.Methods:From March to July 2018, we selected 18 experts such as chairman of Committee of Operating Room of Shanghai Nursing Association, head nurses of Operating Room at ClassⅢ Grade A general hospitals in Shanghai, nurse specialist of pressure injury management team, by purposive sampling as subjects. The consultation form was designed based on search of operation related pressure injury at home and abroad as well as Donabedian structure-process-outcome three-dimensional quality assessment model. Delphi method was used to 2 rounds of expert consultation. Items in all levels were deleted, merged and revised according to expert opinions and to define the evaluation indexes in all levels of nursing quality for pressure injury in Operating Room as well as the weight.Results:This study carried out 2 rounds of expert consultation, with 0.989 for the expert judgment coefficient, 0.956 for the expert familiarity coefficient and 0.973 for the expert authority coefficient. The variation coefficients of second-level indexes and third-level indexes ranged from 0.109 to 0.138 in 2 rounds of expert consultation. The evaluation index system of nursing quality for pressure injury in Operating Room included 3 first-level indexes, 9 second-level indexes and 28 third-level indexes.Conclusions:This study constructs a scientific and reasonable evaluation index system of nursing quality for pressure injury in Operating Room with the method of Delphi which can be used to nursing quality assessment for pressure injury in Operating Room and is in favor of continuous quality improvement of nursing in Operating Room.

Objective: To assess the diagnostic performance of contrast-enhanced spectral mammography (CESM) in suspected breast lesions. Methods: A total of 97 patients with suspected breast cancer identified by clinical examination or screening underwent two-views CESM examination on the basis of digital breast tomosynthesis (DBT) combined with full-field digital mammography (FFDM), and they were finally confirmed by biopsy or pathology. Three senior radiologists analyzed images, including lesion visibility, lesion characteristics, enhancement type, degree of enhancement, BIRDS classification, etc. Finally, based on the pathology, we compared the CESM+DBT+FFDM and DBT+FFDM two models according to sensitivity, specificity and ROC for diagnostic performance. Results: There were a total of 120 lesions. Eighty-nine lesions were malignant, 31 benign; CESM was not enhanced in 2 cases, mild enhancement was performed in 22 cases, moderately intensive in 15 cases, highly intensive in 81 cases, and 2 cases were not enhanced; mass-enhanced in 96 cases, including ring-enhanced in 12 cases, 22 cases of non-mass type. The sensitivities of the combination of CESM and not combination of CESM were 91.0% and 80.9%, respectively, and the specificities were 93.5% and 87.1%, respectively. The area under the ROC curve of combination of CESM was higher than the without combination of CESM (0.923 and 0.900, P<0.05), The difference was statistically significant. Conclusion For suspicious lesions, CESM examination can improve the diagnosis accuracy of breast cancer.