Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

The health financing transition,which is centered on the expansion of health financing scale and the strengthening of public financing responsibility,is regarded as the necessary condition for achieving universal health coverage.Compared with the global trend,China's health financing transition presents obvious characteristics.By integrating multidisciplinary theories,this paper puts forward a multi-level and comprehensive analysis framework,including the system structure and function based on vertical"embeddedness"and horizontal"complementarity",the two-way trade-off mechanism guided by"maintaining and promoting health value and its derived value"and"preventing and resolving health risks and their associated risks",the budget decision-making mechanism centering on the principles of health ethics and the actual governance mode of the government,and the long-term development path with the triple attributes of modern medicine.Accordingly,this paper explores the overall logic and deep reasons for China's health financing transition.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the activation level of neutrophil extracellular trap (NET) in the bile of patients with choledocholithiasis and its clinical significance.Methods:From May 2021 to October 2022, 130 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University were enrolled. The patients were divided into choledocholithiasis group (90 cases) and non-choledocholithiasis group (40 cases), and the choledocholithiasis group was further divided into large stone group (maximum diameter >1 cm, 36 cases) and small stone group (maximum diameter≤1 cm, 54 cases). The bile samples were collected from 130 patients during operation and 16 choledocholithiasis patients with nasobiliary drainage at 24 h after operation.The levels of myeloperoxidase(MPO), neutrophilelastase(NE), and citrullinated histone H3(CitH3) in bile were detected by enzyme-linked immunosorbent assay.The levels of MPO, NE, and CitH3 were compared between choledocholithiasis group and non-choledocholithiasis group, between large stone group and small stone group, as well as between choledocholithiasis patients before ERCP and after ERCP. Mann-Whitney U test and Wilcoxon signed rank test were used for statistical analysis. Results:The levels of MPO, NE and CitH3 in the bile of choledocholithiasis group were 32.6 U/L(28.5 U/L), 30.6 ng/L(35.2 ng/L) and 0.37 μg/L(0.73 μg/L), respectively, which were all higher than those of non-choledocholithiasis group (19.9 U/L(36.4 U/L), 18.2 ng/L(27.4 ng/L), and 0.10 μg/L(0.25 μg/L)), and the differences were statistically significant ( Z=2.91, 3.20 and 3.34; P=0.004, 0.001 and 0.001). The levels of MPO, NE and CitH3 of large stone group were 47.0 U/L(49.4 U/L), 48.4 ng/L(39.5 ng/L) and 0.83 μg/L(1.08 μg/L), respectively, which were all higher than those of small stone group (29.3 U/L(17.5 U/L), 24.0 ng/L(25.8 ng/L), and 0.27 μg/L(0.45 μg/L)), and the differences were statistically significant ( Z=2.01, 3.58 and 3.63; P=0.044, <0.001 and <0.001). The levels of MPO, NE and CitH3 in the bile of choledocholithiasis patients after ERCP significantly decreased compare with those before ERCP (19.4 U/L(19.8 U/L) vs. 33.6 U/L(36.7 U/L), 12.7 ng/L(15.1 ng/L) vs. 22.7 ng/L(25.9 ng/L), 0.05 μg/L(0.12 μg/L) vs. 0.14 μg/L(0.27 μg/L)), and the differences were statistically significant ( Z=3.52, 3.30 and 3.18; all P<0.001). Conclusion:The activation level of NET in the bile of patients with choledocholithiasis increase, while the activation level of NET decrease after ERCP, which indicate that NET may be involved in the formation of choledocholithiasis.

Objective:To investigate the application effect of medical sterile gloves-assisted cutting cloth samples in the repair of finger degloving injury.Methods:The clinical data of patients with finger skin and soft tissue degloving defects treated in Jiangnan Hospital Affiliated with Binjiang College of Zhejiang University of Traditional Chinese Medicine from April 2015 to December 2021 were analyzed retrospectively. Medical sterile gloves were used to make cloth samples of finger defects, and then the dorsal foot flap or toenail flap was cut according to the cloth samples to repair finger defects. The survival of flaps and the appearance of the fingers’ body were observed after surgery, and the patients’ satisfaction was investigated. The finger function was evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Society of Chinese Medical Association.Results:A total of 12 patients with 13 fingers were enrolled. There were 9 males (10 fingers) and 3 females (3 fingers), aged 17-54, average of 37-year-old. There were 5 cases (5 fingers) in the left hand and 7 cases (8 fingers) in the right hand, all with unilateral finger injury. The size of the dorsal flaps and great toenail flaps harvested were appropriate, ranging from 5.5 cm×4.5 cm to 10.5 cm×5.8 cm. After surgery, all patients were regularly followed up for 3-15 months, an average of 7 months. All the dorsal flap and great toenail flap of the foot after surgery survived, and the appearance of the finger body was not bloated. All patients were very satisfied with the appearance and function of the hand, and the finger function was evaluated as excellent in 7 cases and good in 5 cases.Conclusion:The application of sterile gloves-assisted cutting cloth samples for the treatment of finger degloving injury can simplify the procedure, reduce donor damage, make up for the lack as much as needed, and the repaired fingers can obtain better shape and function.

Objective:To investigate the application effect of medical sterile gloves-assisted cutting cloth samples in the repair of finger degloving injury.Methods:The clinical data of patients with finger skin and soft tissue degloving defects treated in Jiangnan Hospital Affiliated with Binjiang College of Zhejiang University of Traditional Chinese Medicine from April 2015 to December 2021 were analyzed retrospectively. Medical sterile gloves were used to make cloth samples of finger defects, and then the dorsal foot flap or toenail flap was cut according to the cloth samples to repair finger defects. The survival of flaps and the appearance of the fingers’ body were observed after surgery, and the patients’ satisfaction was investigated. The finger function was evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Society of Chinese Medical Association.Results:A total of 12 patients with 13 fingers were enrolled. There were 9 males (10 fingers) and 3 females (3 fingers), aged 17-54, average of 37-year-old. There were 5 cases (5 fingers) in the left hand and 7 cases (8 fingers) in the right hand, all with unilateral finger injury. The size of the dorsal flaps and great toenail flaps harvested were appropriate, ranging from 5.5 cm×4.5 cm to 10.5 cm×5.8 cm. After surgery, all patients were regularly followed up for 3-15 months, an average of 7 months. All the dorsal flap and great toenail flap of the foot after surgery survived, and the appearance of the finger body was not bloated. All patients were very satisfied with the appearance and function of the hand, and the finger function was evaluated as excellent in 7 cases and good in 5 cases.Conclusion:The application of sterile gloves-assisted cutting cloth samples for the treatment of finger degloving injury can simplify the procedure, reduce donor damage, make up for the lack as much as needed, and the repaired fingers can obtain better shape and function.

Objective:To explore the surgical method and therapeutic effect of repairing soft tissue defect of digit-tip with single subcutaneous pedicle V-Y advancing flap combined with skin grafting.Methods:From August 2013 to December 2020, 25 soft tissue defects of digit-tip were repaired by a single subcutaneous pedicle V-Y advancing flap combined with pedicle skin grafting. The area of the defects was 0.8 cm× 0.8 cm to 1.6 cm× 1.4 cm. The flaps were harvested from palm or lateral side of the wound and the area of flap was 0.5 cm×1.0 cm to 0.8 cm×2.5 cm. In order to make the flap transfer to a further distance, the subcutaneous fibre connection of the flap was cut-off during the operation. At the same time, cut off 1 side of subcutaneous pedicle. Finally, the advanced distance of the flap reached 0.5-1.2 cm. After the flap harvested, the medium thickness skin was removed for graft to close the donor site from the wrist striations. After the surgery, follow-up visits were conducted regularly by outpatient clinic, or via telephone or WeChat review or by home visit. Throughout the follow-up, the flap appearance, sensation and recovery of the function of digital joint were observed, together with the patient satisfaction. Results:After the surgery, the postoperative follow-up lasted for 4 months to 8 years. All 25 flaps and skin grafts were survived in first stage wound healing. The flaps and skin grafting areas had excellent texture. The fingerprint had been reconstructed with good appearance. The TPD was 4-9 mm, the functions of digital joint recovered well, and there was no complain about a discomfort at the donor site. According to the evaluation standard of Michigan hand function questionnaire, all 25 patients were very satisfied with the overall appearance and function of the hand. According to Total Angle of Motion (TAM) evaluation standard, finger mobility was excellent in all 25 patients.Conclusion:Subcutaneous V-Y advancing flap combined with skin grafting is an ideal method for repairing soft tissue defect of digit-tip. The surgery characterises a simple flap cutting, less traumatic damage, long advancing distance of flap and good repair effect.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.
Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant, Newborn ; Obstetrics ; Patient Discharge ; Pregnancy ; Retrospective Studies

Objective:To investigate whether polyethylene glycol hydrogel films (PHFs) can be used as a carrier for the expansion of corneal epithelial cells (CECs) in vitro and whether PHFs can be used in the treatment of limbal stem cell deficiency (LSCD). Methods:Sebacoyl chloride, dihydroxyl PCL and glycerol ethoxylate were used to synthesize PHFs.The thickness, transmittance and mechanical tensile properties of PHFs were measured.Four clean-grade New Zealand white rabbits were selected to culture primary limbal epithelial cells.The expression of keratin marker AE1/AE3 and stem cell marker p63 in the cultured cells were observed under a fluorescence microscope.The cells were divided into negative control group cultured with common cell culture solution, positive control group cultured with cell culture solution containing 100 μmol/L H 2O 2, and PHFs+ CECs group lined with PHFs cultured with common cell culture solution for 24 hours.The proliferation and apoptosis of cells in the three groups were observed by MTT and TUNEL staining, respectively.Fifteen clean-grade New Zealand white rabbits were divided into control group, PHFs group and PHFs+ CECs group by random number table method, with 5 rabbits in each group.LSCD model was constructed in the three groups.The control group was not given any treatment after modeling.In PHFs group, empty PHFs were placed on the corneal surface of rabbits.In PHFs+ CECs group, tissue-engineered grafts constructed with CECs after passage implanted on PHFs were placed on the corneal surface of rabbits.The corneal defect area of rabbits was detected and scored by fluorescein sodium staining.The histological characteristics of rabbits corneal epithelium was observed by hematoxylin-eosin staining.The use and care of animals complied with Guide for the Care and Use of Laboratory Animals by the U. S.National Research Council.The experimental protocol was approved by the Research and Clinical Trial Ethics Committee of The First Affiliated Hospital of Harbin Medical University (No.2021006). Results:The synthetic PHFs were with a thickness ≤150 μm, a tensile strength about 6 MPa, and a transmittance over than 99% in the range of 400-700 nm.Most of the cells from primary culture of limbal tissue were positive for AE1/AE3 and p63.MTT test results showed that the A490 value of PHFs+ CECs group, negative control group and positive control group was 0.59±0.01, 0.65±0.07 and 0.06±0.04, respectively, showing a statistically significant overall difference ( F=12.25, P<0.05). The A490 values of PHFs+ CECs group and negative control group were significantly higher than that of positive control group, and the differences were statistically significant (both at P<0.05). TUNEL test results showed that there was a significant difference in the TUNEL-positive cell rate among the three groups ( F=13.45, P<0.05), and the rates of TUNEL-positive cells in PHFs+ CECs group and negative control group were significantly lower than that in positive control group (both at P<0.05). Fluorescein sodium staining results showed that with the extension of postoperative period, the corneal fluorescein sodium staining score of the three groups decreased, which decreased successively in control group, PHFs group and PHFs+ CECs group.Hematoxylin-eosin staining showed fewer irregularly shaped corneal epithelial cells in the control group, and sparse single layer of corneal epithelial cells in some areas of the PHFs group.In PHFs+ CECs group, the corneal epithelium coverage was the largest, and the cell layers increased to 3-5, and the cells were with regular morphology and in close arrangement. Conclusions:PHFs have enough toughness, high transmittance and can expand corneal epithelium in vitro.PHFs are suitable for corneal epithelial transplantation and can promote the repair of corneal epithelium in rabbit model of LSCD.