BACKGROUND:3D organoids have characteristics that resemble physiological tissues and to some extent mimic organ function,making them excellent models for applications ranging from basic development/stem cell research to personalized medicine. OBJECTIVE:To review and discuss the types of diseases and application areas such as tumor modeling that organoids can be applied to,as well as their regulatory status and challenges. METHODS:With"organoid,stem cell,disease model,3D printing technology,medical field"as Chinese and English search terms,we searched PubMed,Elsevier,WanFang,and CNKI databases to summarize and analyze organoid products at home and abroad,summarize the application of organoid technology in the medical field,and prospect the future development of organoid products in the medical field. RESULTS AND CONCLUSION:Organoids can break the limitations of traditional cell and animal models,avoid the ethical problems existing in clinical research,and have a high similarity to the source organ,a more similar performance to the physiology and pathology of human systems,and genetic stability,which has great advantages in current research.Organoids have been applied in the following fields:efficacy evaluation studies(preclinical models),including intestinal organoids,kidney organoids,liver organoids,gallbladder organoids,lung organoids,brain organoids,heart organoids,skin organoids,and reproductive system organoids;research on infectious diseases;cancer research and precision therapy;regenerative medicine;immune organoids.Although the United States,the European Union and China do not have perfect regulatory provisions,they are trying to promote the formulation of organoid regulatory laws and regulations.In China,although no organoid medical device products have been listed for the time being,its related regenerative medicine products have made breakthroughs.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

Objective Fasting hypometabolism regulation technology has broad application potential in long-term space flight and survival in extreme extraterrestrial environments.In-depth research on the substrate conversion of energy metabolism and the formation of new steady states under fasting hypometabolism will provide theoretical basis and experimental data support for formulating effective prolonged fasting application mode.Methods 30 SD rats were randomly divided into control group and fasting group(fasting for 1,2,3,and 5 days).Blood biochemical examination,qRT-PCR,and western blotting were performed to analyze the body weight,blood biochemistry,and expression changes of genes and proteins related to glucose and lipid metabolism during different fasting periods.Results Prolonged fasting significantly reduced the body weight,blood glucose,and triglyceride levels of rats;increased the blood ketone level,and replaced glucose as the main energy substance in the body.There are temporal and tissue-specific changes as a whole.Hepatic and renal gluconeogenesis play major roles respectively during different fasting periods.As the fasting time prolongs,the level of hepatic gluconeogenesis gradually decreases,the content of FFA in the blood increases,the expression level of genes related to fat synthesis decreases,fatty acid oxidation is enhanced,and the expression level of the key gene HMGCS2 for ketone body generation increases.Conclusion During prolonged fasting,there is a significant conversion of glucose-ketone energy supply substrates,and a new steady state of energy metabolism mainly supplied by ketone bodies is formed within 2-5 days of fasting.The body maintains a low metabolic state by regulating changes in key genes in pathways such as glucose and lipid metabolism.

Objective:To explore the characteristics, prevention and treatment strategies of lower urinary tract injury in transvaginal reconstructive pelvic surgery (vRPS).Methods:A retrospective analysis was conducted on 24 patients who suffered lower urinary tract injuries occuring in vRPS from January 2005 to June 2021, among which 4 cases were referred to our hospital from other hospitals.Results:(1) In our hospital, 1 952 patients underwent vRPS for anterior and (or) middle pelvic organ prolapse during that study period, with a 1.0% (20/1 952) incidence of lower urinary tract injuries occurring in 20 cases. (2) Ureteral injuries were observed in 14 cases who underwent transvaginal high uterosacral ligament suspension (1.4%, 14/966). The symptoms were relieved after the removal of sutures. (3) Bladder injuries occurred in 6 cases in our hospital, with 4 cases (0.7%, 4/576) in anterior transvaginal mesh surgery (aTVM), one (0.4%, 1/260) in colpocleisis, and one (0.7%, 1/150) in apical suspension for fornix prolapse. An additional 4 cases of bladder injury were referred to our hospital after aTVM. Among the 8 cases of bladder injury during aTVM, 2 cases were intraoperative incidents. Cystoscopy confirmed that the superficial branch or puncture rod of anterior vaginal mesh had penetrated into the bladder. Re-puncturing and placement of the mesh were successfully performed. No abnormalities were observed during a follow-up period of 4-5 years. Postoperative bladder injuries were identified in 6 cases, characterized by mesh erosion into the bladder and formation of calculi. These injuries were confirmed between 6 months to 2 years after vRPS. The exposed mesh and calculi in the bladder were removed through laparotomy or cystoscopy, followed up for 2-12 years. One case experienced slight re-erosion of mesh to the bladder.Conclusions:Lower urinary tract injuries are difficult to avoid in vRPS, particularly in transvaginal high uterosacral ligament suspension and aTVM. However, the incidence is low. Lower urinary tract injuries during vRPS could be easily detected and managed intraoperatively because of the use of cystoscopy. As long-term postoperative complications, erosion of transvaginal mesh to lower urinary tract postoperatively could be treated correctly, seldom with severe sequelae.

Objective:To investigate the clinical value of prospective ECG-gated high-pitch protocol scanning of third generation DSCT in the diagnosis of pediatric congenital heart disease (CHD).Methods:A total of 243 children with confirmed CHD who were expected to undergo surgical treatment were prospectively collected and randomly divided evenly into 3 groups, with first group for prospective ECG-gated high-pitch scanning in third generation DSCT (Flash 3rd), second group for prospective ECG-gated high-pitch scanning in second generation DSCT (Flash 2nd) and third group for prospective sequential scanning in third generation DSCT (Sequence 3rd). The SD value and SNR of aortic root and pulmonary artery of each child were recorded. The 5-point system is adopted with subjective scoring. Based on the result of operation, the diagnosis accuracy in 3 groups was analyzed. Results:The E values in Flash 3rd, Flash 2nd and Sequence 3rd group were 0.24 (0.19, 0.27), 0.11 (0.10, 0.14) and 0.44 (0.39, 0.48) mSv ( H=207.04, P<0.05), respectively. Subjective scores of group Flash 3rd and Sequence 3rd were significantly higher than that of group Flash 2nd [4 (4, 4) vs. 4(3, 4) vs. 3(3, 3), H=124.05, P<0.05] and no difference between these two groups. SD value of aortic root and pulmonary artery of group Flash 3rd and Sequence 3rd were significantly lower than that of group Flash 2nd( H= -40.27-33.38, P<0.05). SNR of aortic root and pulmonary artery of group Flash 3rd was significantly higher than that of group Flash 2nd and Sequence 3rd ( H=-0.90-51.42, P<0.05). Diagnosis accuracy of intracardiac malformation for group Flash 2nd was significantly lower than that of Flash 3rd and Sequence 3rd (77.7%, 90.9%, 88.9%, K=9.36, P<0.05), and there was no significant difference between the latter two groups. There was no difference in diagnosis accuracy of extracardiac malformation among 3 groups (88.6%, 94.8%, 92.2%, K=3.11, P=0.21). Conclusions:The prospective ECG-gated high-pitch scanning in third generation DSCT can take into account radiation dose and image quality, which has important clinical value in the diagnosis of CHD.

Performance appraisal of public hospitals have given a guidance for the development of public hospitals at all levels.A Class A tertiary hospital reviewed the problems in the development of the hospital at the present stage and focused on the following four aspects:①insufficient fine management;②No clear orientation of discipline development;③The bottleneck of the improvement of medical operation efficiency;④New challenges in the reform of payment mode.The tertiary hospital launched a fine management practice in May 2022,in order to solve the problems by taking the Department of Surgery as a pilot area,laying the foundation for fine management through information system construction,improving the efficiency of medical operation through management process optimization,improving the overall competitiveness of disciplines through the construction of sub-specialty and Discipline Alliance and adjusting the performance appraisal index system to play the role of performance incentives.The measures effectively improve the overall capacity and efficiency of hospital medical services and help the hospital to achieve high-quality development.

Objective The applications of personalized abutments and abutment crown bridge products have increased year by year,but there is no clear requirement for clinical evaluation of the same variety of such products.This study mainly introduces the clinical evaluation concerns of personalized abutments and abutment crown bridge products,in order to provide reference for the declaration and registration of such products.Methods The clinical evaluation of personalized abutments and crown bridge products are summarized,and the research content of clinical evaluation is clarified.Results The clinical evaluation requirements that need to be considered by enterprises are introduced.Conclusion Personalized abutment and abutment crown bridge products can refer to this study when they are launched in China,mainly using in vitro performance comparison tests for equivalence verification.

Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.