Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

ObjectiveTo explore the construction of a risk assessment indicator system for common infectious diseases in Shanghai’s childcare institutions, and to provide a reference standard for the prevention and control of infectious diseases, staff training and system construction in childcare institutions. MethodsBy combining the Delphi method with the literature review and expert consultation, the hierarchical dimensions and items at all levels of the risk assessment indicator system for common infectious diseases in Shanghai’s childcare institutions were constructed, and the weighting coefficients were determined by analytic hierarchy process. ResultsA total of 14 experts from the field of childcare institutions, infectious disease control, child healthcare and health supervision participated in the Delphi consultation. The system consisted of four core dimensions: organizational management, team building, hardware equipment, and infectious disease surveillance and disposal, with the weighting coefficients of 0.285 9, 0.261 6, 0.204 3 and 0.248 2, respectively. The evaluation indicator system consisted of 4 primary indicators, 15 secondary indicators and 45 tertiary items. The positivity coefficients of the two rounds of Delphi consultation were 0.93 and 1.00, the authority coefficients were both 0.81, and the Kendall’s coefficient of concordance were 0.44 and 0.49, respectively (P<0.01). ConclusionThe high expert engagement and coordination indicate that organizational management and team building remain the critical priorities for infectious disease prevention and control in Shanghai’s childcare institutions. It is recommended to strengthen financial investment, improve institutional mechanisms, and enhance personnel reserves and capacity building for healthcare teachers, thereby systematically upgrading the infectious disease control capabilities of childcare institutions.

Objective To investigate the safety and efficacy of target calyx pretreatment technique in the treatment of complete staghorn calculi by endoscopic combined intrarenal surgery(ECIRS).Methods Clinical data of 21 patients with complete staghorn calculus treated by ECIRS from October 2019 to September 2021 in our hospital were retrospectively analyzed.There were 8 cases in the left side and 12 cases in the right side.One case of bilateral kidney calculus was given right side treatment in the first stage.The stone density was(1101±185)HU.The operation was performed by two surgeons.Under general anesthesia,the patient was placed in an oblique supine lithotomy position.The target calyx was designed according to preoperative imaging examination.The stone in the target calyx was broken up by flexible ureteroscope in advance to expose the papillary dome.Percutanous nephrostomy of the target calyx was performed,and F18 or F20 percutaneous work access was established under surveillance by using flexible ureteoscope and ultrasound.Results The operation was successfully accomplished in one stage in all the 21 cases.The mean operation time was(121.8±21.2)min,the postoperative hemoglobin reduction was(9.38±4.36)g/L,the postoperative hospital stay was(4.4±1.4)d,and the postoperative stone free rate(SFR)was 85.7％(18/21).A total of 6 patients had postoperative complications,including 1 case of bleeding requiring blood transfusion,3 cases of fever,1 case of hydrothorax,and 1 case of postoperative pain in the operative area requiring analgesic treatment.Conclusion For complete staghorn calculus,using flexible ureteroscope to pretreat stones of target calices and then puncturing to establish percutaneous renal working channel can significantly increase the success rate of surgery and the immediate postoperative stone free rate,reduce the number of percutaneous renal channels,and improve the safety of surgery.

Objective:To explore the force distribution on the maxillary dentition when the first and second molars distalized simultaneously with different step sizes using clear aligners in vitro in order to provide a theoretical basis for the rational design of molar distalization. Methods:Clear aligners were designed to simultaneously distalize the maxillary first and second molars bilaterally, with rectangular attachments placed on the buccal surfaces of the first and second premolars, as well as the second molars. Based on different step sizes, the aligners were divided into three groups: Group A (0.15 mm per step), Group B (0.20 mm per step), and Group C (0.25 mm per step). Ten aligners were fabricated for each group using 0.76 mm thick polyethylene terephthalate glycol (PET-G) sheets. A three-dimensional force measurement system was used to measure the forces exerted on each tooth by the aligners, the first and second molars served as the target teeth and the remaining teeth as anchorage teeth. The three-dimensional force data were compared among the three groups.Results:In the mesiodistal direction, the forces on the central and lateral incisors were relatively small among all three groups, with no statistically significant differences ( P>0.05). However, significant differences were observed in the forces on the canines, first premolars, second premolars, first molars, and second molars ( P<0.05). The distal forces on the second molars in Groups B and C were (6.13±1.45) N and (6.83±1.58) N, respectively, significantly higher than that in Group A [(3.51±1.01) N] ( P<0.05). The distal force on the first molars in Group C [(6.62±0.89) N] was significantly higher than that in Groups A and B ( P<0.05). The mesial reactive forces on the first and second premolars in Groups B and C were significantly higher than those in Group A ( P<0.05). The mesial reactive force on the canines in Group C [(-2.98±1.33) N] was significantly higher than that in Group A [(-1.69±0.68) N] ( P<0.05), while there were no significant differences between Groups B and C in the forces on the canines, first premolars, and second premolars ( P>0.05). In the buccolingual direction, there were no statistically significant differences in the forces on the central and lateral incisors among three groups ( P>0.05), but significant differences were observed in the forces on the canines, second premolars, and second molars ( P<0.05). The buccolingual forces on the canines, second premolars, and second molars in Group B were (-0.56±0.54), (-2.07±0.95), (1.13±0.55) N, respectively, significantly higher than those in Group A ( P<0.05), but there were no significant differences compared to Group C ( P>0.05). Compared to the mesiodistal and buccolingual forces, the vertical forces on the target and anchorage teeth were relatively small in all three groups. Conclusions:When using 0.76 mm thick PET-G sheets to fabricate clear aligners for simultaneous molar distalization, a step size of 0.20 mm per step is recommended. To prevent buccal tipping of the molars during distalization, it is advisable to design lingual displacement for the molars and buccal displacement for the adjacent anchorage teeth to counteract the unfavorable forces, with attachments placed on the primary anchorage teeth.

Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".

Objective To analyze the equity and efficiency of resource allocation for management and treatment of severe mental disorders in Shanghai in 2020, and to provide a foundation for making relevant policies. Methods Data on resource allocation for the management and treatment of severe mental disorders in 17 district-level mental health institutions in 2020 were collected. The Gini coefficient was used to evaluate the equity of resource allocation by population and geographic area, and data envelopment analysis was carried out to analyze the equity of resource allocation. Results The Gini coefficients of special funds, psychiatric medical staff and actual open beds according to population were 0.24, 0.25 and 0.27, respectively. The Gini coefficients according to area were 0.54, 0.62 and 0.64, respectively. The average efficiency of resource allocation was 0.865. There were 5 institutions where DEA was effective, accounting for 29.41%. There were 12 institutions where DEA was non-effective, accounting for 70.59%. Conclusion The equity of resources allocation for the management and treatment of severe mental disorders according to population is good, but the equity of allocation based on geographic area is not high. The efficiency of resource allocation needs to be further improved. It is suggested that the resource allocation should be optimized to promote the fairness and efficiency of resource allocation for the management and treatment of severe mental disorders.

Objective:To assess the safety and feasibility of complete lateral position endoscopic combined intra-renal surgery (ECIRS) in treatment of staghorn kidney calculi.Methods:The clinical data of 105 patients with staghorn kidney calculi from March 2016 to July 2022 in the First Hospital of Shanxi Medical University were retrospectively analyzed. Among them, 55 patients were treated with lateral position percutaneous nephrolithotomy (PCNL) (PCNL group), and 50 patients were treated with complete lateral position ECIRS (ECIRS group). The operative time, removal time of double J-tube, postoperative hospital stay, postoperative hemoglobin decrease value, operative complications (using Clavien-Dindo grading criteria), additional postoperative intervention and calculi free rate were compared between two groups.Results:Both groups of patients were successfully operated. The operative time, postoperative hemoglobin decrease value and rate of additional postoperative intervention in ECIRS group were significantly lower than those in PCNL group: (98.3 ± 19.1) min vs. (103.4 ± 16.5) min, (9.34 ± 3.04) g/L vs. (12.55 ± 4.75) g/L and 8.00% (4/50) vs. 21.82% (12/55), the calculi free rate was significantly higher than that in PCNL group: 90.00% (45/50) vs. 74.55% (41/55), and there were no statistical differences ( P<0.05 or <0.01); there were no statistical differences in the removal time of double J-tube, postoperative hospital stay, incidence of Clavien-Dindo≥ grade Ⅱ operative complications between two groups ( P>0.05). Conclusion:The complete lateral position ECIRS is a safe and effective treatment for staghorn kidney calculi, and is a good complement to the ECIRS technique because of its high stone free rate in phase Ⅰ, low complication incidence and easy dissemination.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To screen plasma exosomal protein molecular markers in patients with spinal cord injury (SCI) by applying Label-Free quantification and bioinformatics analysis.Methods:Fifty plasma specimens from the First Affiliated Hospital of Nanjing Medical University (from January 2021 to June 2022) were collected from SCI patients and healthy people, respectively. Plasma exosomes were isolated using ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blot. Plasma exosomal differentially expressed proteins (DEPs) were analyzed using Label-Free quantitative proteomics, and DEPs were characterized, annotated, and enriched based on Gene Ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) databases. The screened DEPs were validated by western blot and enzyme linked immunosorbent assay (ELISA) using plasma exosomal specimens.Results:According to the spinal cord injury classification of the American Spinal Injury Association, 14 cases were grade A, 19 cases were grade B, 12 cases were grade C, and 5 cases were grade D. Plasma exosomes of SCI patients and control groups showed typical cup-like morphology, with diameters mainly ranging from 30-200 nm. A total of 493 exosomal proteins were identified by Label-Free quantification, and 126 proteins were screened for differential expression, of which 38 were up-regulated and 88 were down-regulated. GO annotation revealed that DEPs were mainly involved in functions such as protein activation cascade, complement activation and immune response. KEGG pathway analysis revealed that DEPs were involved in biological pathways such as complement and coagulation cascade reactions, proteasome and neurodegenerative disease pathways. Two candidate proteins, APOB and S100A9, were initially screened based on quantitative results from proteomics and bioinformatics analyses. Western blot results showed that the relative expression of S100A9 protein in plasma exosomes of 30 SCI patients (1.62±0.19) was elevated compared with that of 30 control groups (0.86±0.24), and the difference was statistically significant ( t=8.55, P<0.001), while the relative expression of APOB protein (1.06±0.13 and 1.02±0.23) were not statistically significant ( t=0.46, P=0.653). The results of ELISA analysis showed that the expression of S100A9 in plasma exosomes of patients with different degrees of SCI (grade A 197.7±11.7 pg/ml, grade B 151.7±15.2 pg/ml, grade C 136.3±14.7 pg/ml) had statistical significance ( F=69.94, P<0.001), the higher the severity of SCI, the higher the expression of S100A9 in plasma exosomes (A vs. B, q=13.11, P<0.001; A vs. C, q=15.66, P<0.001; B vs. C, q=4.19, P=0.005). Conclusion:S100A9 is a potentially valid plasma exosomal molecular marker for assessing the severity of SCI.