Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Objective:To summarize and analyze the modalities and experience of retrograde distal perfusion with distal perfusion catheter (DPC) via cannulation of the posterior tibial artery in veno-arterial extracorporeal membrane oxygenation(V-A ECMO).Methods:The clinical data of 15 patients who were treated with V-A ECMO and underwent DPC placement via the posterior tibial artery in our hospital from January 2022 to June 2023 were retrospectively analyzed.Results:The V-A ECMO catheterization method in 15 patients was percutaneous puncture catheterization, and all of them underwent surgical incision to indwelling retrograde DPC through the posterior tibial artery: 6 cases of preventive catheterization, 9 cases of remedial catheterization, the success rate of one-time catheterization was 93.33%, and the type of catheter was mainly 6 F sheath (66.67%). There was no ALI in preventive catheterization, and one case of osteofascial compartment syndrome occurred in remedial catheterization, and the catheterization time was (20.73 ± 3.47) min.Conclusions:In V-A ECMO, placement of DPC via the posterior tibial artery for retrograde distal perfusion is perfectly feasible, and has a high success rate, which can prevent or treat lower extremity ischemia.

This study aims to enhance the activation level and efficiency of second-generation chimeric antigen receptor-T(CAR-T)cells in killing tumor cells by modifying the lymphocyte-specific protein tyrosine kinase(LCK)structure of second-generation CAR,so as to lay the foundation for the preparation of novel second-generation CAR-T cells.Using genetic engineering techniques,lentiviral vectors for CD137-LCK2 CAR and CD137-PYAP2 CAR targeting human epidermal growth factor receptor 2(HER2)were constructed,and CD137-LCK2 and CD137-PYAP2 CAR-T cells were prepared by lentiviral packaging and infection of activated T cells.The differences between them in terms of CAR expression level,activating molecule CD 137 expression,phenotypic distribution,cytokines secretion,and killing effect on HER2-expressing tumor cells were detected and compared using flow cytometry,enzyme-linked immunosorbent assay,and cytotoxicity assay,respectively.Compared with the second-generation CD137 CAR-T cells,the structurally modified CD137-LCK2 and CD137-PYAP2 CAR-T cells targeting HER2 can increase the expression of activating molecule CD 137,increase the secretion of cytokine IFN-γ,and enhance the killing ability of target antigens;at the same time,these cells can be maintained in the memory state and can rapidly activate proliferation and differentiation after stimulation by antigen.In conclusion,CD137-LCK2 and CD137-PYAP2 CAR-T cells targeting HER2 are expected to activate and exert anti-tumor effects more effectively than second-generation CD 137 CAR-T cells.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective:To analyze the therapeutic effect of 3D printing technology combined with locking plate fixation on femoral shaft fracture in patients with femoral deformity.Methods:The clinical data of 33 patients with femoral shaft fracture with femoral deformity who met the inclusion criteria and underwent locking plate fixation in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from June 2014 to December 2020 were retrospectively analyzed. The patients were divided into 3D printing group ( n=18) and control group ( n=15) according to whether 3D printing was performed before operation. The 3D printing group including 11 males and 7 females with an age of (46.78±13.76) years.The control group including 9 males and 6 females with an age of (48.20±14.27) years.The operation time, intraoperative blood loss, fracture healing time and complications of the two groups were recorded. Visual analogue scale (VAS) scores of pain were evaluated before and 6, 12, 24, 48 and 72 h after operation. According to the Harris hip score, the Hospital for Special Surgery (HSS) knee score and The MOS 36-item short-from Health Survey (SF-36), the hip and knee function and quality of life of the patients before and 12 months after injury were evaluated. The measurement data were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data between groups was conducted by Chi-square test or Fisher exact probability. Results:The operation time, intraoperative blood loss, and incidence of complications in the 3D printing group were (91.50±9.07) min, (191.11±16.01) mL, and 0(0/18), respectively, and those in the control group were (118.07±14.19) min, (270.27±17.59) mL, and 26.7% (4/15), the differences between the two groups were statistically significant ( P <0.05). The pain VAS scores of the 3D printing group were significantly better than those of the control group at 6, 12, 24, 48, and 72 h after operation ( P<0.05). There were no differences in fracture healing time and preoperative pain VAS between the two groups( P>0.05). There were no significant differences in hip function, knee function and quality of life scores between the two groups before injury and 12 months after injury( P>0.05). Conclusion:In the treatment of femoral shaft fractures in patients with femoral deformity with locking plate fixation, the application of 3D printing technology can be used for preoperative design and plate preshaping, which can shorten the operation time, reduce the amount of intraoperative blood loss, reduce the VAS of pain and the incidence of complications, improve the satisfaction of surgery, and provide a new option for the treatment of femoral shaft fractures in patients with femoral deformity.

Objective:To investigate the effect of gallic acid on the morphology, proliferation and cell cycle of keloid fibroblasts, as well as on collagen contraction and the transforming growth factor-β (TGF-β) /Sma- and Mad-related proteins (Smads) signaling pathway, and to explore the role and mechanisms of action of gallic acid in the treatment of keloids.Methods:From August to December 2022, 3 keloid tissue samples were collected from 3 patients with clinically and pathologically confirmed keloids after surgery in the Department of Dermatologic Surgery, Wuhan No.1 Hospital. Primary fibroblasts were isolated and cultured by using the tissue culture method, and 3- to 8-passage fibroblasts were used for subsequent experiments. Cultured keloid fibroblasts were divided into 4 groups: low-, medium- and high-dose gallic acid groups treated with 0.025, 0.05 and 0.1 mg/ml gallic acid respectively, and a control group cultured with Dulbecco′s modified Eagle′s medium (DMEM) containing 10% fetal calf serum. After 24-, 48-, and 72-hour treatment, cellular proliferative activity was evaluated by cell counting kit 8 (CCK8) assay, and collagen contraction by using a three-dimensional culture method. After 24-hour treatment in the above groups, pictures were taken using a differential interference inverted fluorescence microscope, and changes in the cell cycle were analyzed by flow cytometry. Some keloid fibroblasts were divided into 2 groups: an experimental group (high-dose gallic acid group) treated with 0.1 mg/ml gallic acid, and a control group cultured with DMEM containing 10% fetal calf serum. After 24-hour treatment, enzyme-linked immunosorbent assay (ELISA) was performed to determine the changes in supernatant concentrations of TGF-β1, TGF-β2, and TGF-β3 in the two groups, real-time fluorescence-based quantitative PCR to detect the relative mRNA expression levels of TGF-β1, TGF-β2, TGF-β3, Smad2, Smad3, Smad4, and α-smooth muscle actin (α-SMA). Statistical analysis was carried out using t test, one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Compared with the control group, the gallic acid groups showed gradual changes in the shape of keloid fibroblasts under the microscope as the dose of gallic acid increased, including gradually shrinking cell bodies, enlarged intercellular spaces, cell atrophy, increased number of apoptotic cells, etc. CCK8 assay showed that the cellular proliferative activity changed significantly as the dose of gallic acid increased and the treatment time was prolonged ( Fgroup = 78.31, P < 0.001; Ftime = 4.17, P = 0.037), and the proliferative activity of keloid fibroblasts was significantly lower in the high-dose gallic acid group than in the control group at 24, 48, and 72 hours (all P < 0.05). The three-dimensional culture showed that different degrees of collagen contraction occurred in all groups over time, marked collagen contraction was observed in the control group, and a lower degree of collagen contraction in the gallic acid groups; the collagen contraction indices were significantly lower in the medium- and high-dose gallic acid groups than in the control group at 24, 48, and 72 hours (all P < 0.05). Flow cytometry showed that the cell apoptosis rates were significantly higher in the low-, medium- and high-dose gallic acid groups (38.68% ± 3.05%, 41.82% ± 2.19%, 43.56% ± 3.58%, respectively) than in the control group (12.58% ± 1.56%, all P < 0.001) after 24-hour treatment; compared with the control group, the medium- and high-dose gallic acid groups showed significantly decreased proportions of cells in the G0/G1 phase (both P < 0.01), but significantly increased proportions of cells in the S phase and G2/M phase (all P < 0.05). ELISA revealed that the TGF-β1 concentration was significantly lower in the high-dose gallic acid group (758.58 ± 31.42 pg/ml) than in the control group (1 081.30 ± 44.72 pg/ml, t = 11.81, P<0.001), there was no significant difference in the TGF-β2 concentration between the high-dose gallic acid group (71.05 ± 7.40 pg/ml) and the control group (76.43 ± 6.51 pg/ml, t = 1.09, P = 0.317), while the TGF-β3 concentration was significantly higher in the high-dose gallic acid group (5.70 ± 3.87 pg/ml) than in the control group (0.00 ± 0.00 pg/ml, t = 2.94, P = 0.026). As real-time fluorescence-based quantitative PCR revealed, the high-dose gallic acid group showed significantly decreased mRNA expression levels of TGF-β1, Smad2, Smad3, Smad4, and α-SMA (all P < 0.05), but significantly increased mRNA expression level of TGF-β3 ( t = 6.78, P = 0.002) compared with the control group; however, there was no significant difference in the TGF-β2 mRNA expression level between the above two groups ( t = 0.05, P = 0.962) . Conclusion:Gallic acid could change the cell cycle, inhibit the proliferative activity, promote apoptosis and change the shape of keloid fibroblasts, and thus inhibit scar formation and contraction, which may be related to the inhibition of TGF-β/Smads signaling pathway.

Objective:To analyze the policy tools designed for function orientation and development of China′s infectious disease hospitals, in order to provide references for formulating and optimizing the functional implementation and sustainable development policies of these hospitals.Methods:Consulting the website of Peking University Law and official websites on health, and using such keywords as " medical institutions, infectious diseases, hospitals for infectious diseases, public health emergencies, specialized hospitals", and searching the national policy texts on the functions and development of infectious disease hospitals issued from December 1991 to January 2023. By means of Rothwell and Zegveld′s policy tool classification method, Nvivo 11 Pro software was used to analyze the text content from the dimensions of demand-type, supply-type, and environmental-type policy tools.Results:A total of 41 policy texts were included and 204 codes were obtained through text analysis. Of all the tools, environmental and supply-oriented policy tools were used the most, being 104 (50.99%) and 95 (46.56%) respectively, while demand-oriented policy tools were used the least, only 5 (2.45%). Of all the environmental-oriented policy tools, " goal planning" was the most used, being 34 (16.67%), while " publicity and guidance" was less used, only 4 (1.96%). Among the supply-oriented policy tools, " clarifying the reporting and handling service functions of public health emergencies" was the most widely used, being 34 (16.67%), while " Informationization" and " infrastructure construction" was less used, being 8 (3.92%) and 6 (2.94%) respectively. Few of the demand-oriented policy tools were in use, as " government purchase" and " medical insurance support" were both 2 (0.98% each), and " social medical care" was only 1 (0.49%).Conclusions:The distribution of three types of policy tools for function and development of infectious disease hospitals is unbalanced, the use of environmental and supply-oriented policy tools is excessive and internal structure is unbalanced. The proportion of environmental-oriented policy tools needs to be adjusted, and the frequency of use of supporting tools such as relevant standards, norms, incentives, supervision and publicity should be increased. Supply-oriented policies need to be further optimized, especially in terms of personnel training, funding, information technology and infrastructure construction. Demand-oriented policy tools are seriously underused and need to be further developed.

Objective:To investigate the prevalence of enterovirus infection and its clinical characteristics in neonatal febrile cases.Methods:A total of 308 neonates in the neonatal ward of Kunming Children′s Hospital with febrile symptoms from March 2018 to February 2019 were selected for the study.Fecal specimens and some (271) cerebrospinal fluid specimens were collected from all neonates.Enterovirus was respectively detected in feces and cerebrospinal fluid by using reverse transcription-polymerase chain reaction (RT-PCR) method.The rate of enterovirus infection in febrile neonates was clarified.They were divided into enterovirus infection group ( n=91) and no enterovirus infection group ( n=217). The clinical data of the subjected neonates in the two groups were analyzed and the clinical manifestations of the neonates and their laboratory findings were compared statistically. Results:Ninety-one enteroviruses (90 enterovirus were general type, and 1 was coxsackievirus A16 type) were detected in 308 children, accounting for 29.55% of all neonates.Viral RNA was detected in only 1 case [0.37% (1/271)]of all examined cerebrospinal fluid specimens, which was significantly lower than the detection rate of 29.55% (91/308) in fecal specimens.There were no fatal cases, but there was one severe case in enterovirus infection group.Except for the severe case which was discharged automatically, all of them improved or healed and discharged from hospital.The clinical manifestations of the enterovirus infection group were non-specific statistically compared with the non-enterovirus infection group(all P>0.05), except for respiratory symptoms and skin rash(all P<0.05). The incidence of enterovirus infection was significantly seasonal[83.52%(76/91)in summer and autumn]. Conclusion:In the epidemic season of enterovirus, it is recommended to list fecal enterovirus as a routine test item to improve the accuracy and timeliness of diagnosis and treatment, and avoid the application of unnecessary antibiotics and the outbreak of enterovirus in the neonatal ward.

Objective:To compare the clinical effects of acute shortening-lengthening technique with antibiotic calcium sulfate-loaded bone transport technique for the treatment of segmental tibial defects after trauma.Methods:The clinical data of 58 patients with large tibial defects treated by Ilizarov technique in Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from May 2014 to December 2019 were retrospectively analyzed. Thirty patients were treated by acute shortening-lengthening (group A), and they were divided into those who were successful in one-time shortening during operation (group A1) and those who needed gradual shortening after operation (group A2) according to different shortening conditions. And 28 patients by antibiotic calcium sulfate-loaded bone transport (group B). The external fixation time (EFT) and external fixation index (EFI) of the two groups were compared. Bone defect healing and limb functions were evaluated according to the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. Complications were compared by Paley classification. The measurement data of normal distribution were expressed as ± s, and t-test was used for comparison between groups; the count data were expressed as n(%), and the chi-square test, Fisher exact probability method or Mann-Whitney U test were used for comparison between groups. Results:Patients were followed for(27.5±5.1)months. There was no significant difference in EFT, EFI, bone defect healing and limb functions between the two groups( P>0.05). The incidence of Grade-Ⅱ[41.2% (7/17)], Grade-Ⅲ [47.1% (8/17)] pin-tract infection in group A1 and Grade-Ⅱ[46.2% (6/13)], Grade-Ⅲ pin-tract [53.8% (7/13)] in group A2 was significantly higher than those in group B[14.3% (4/28)], [17.9% (5/28)] ( P<0.05). The number of complications per capita in group A1 [(1.4±0.3) times/case] and in group A2 [(1.5±0.3) times/case]was significantly higher than that in group B [(1.1±0.5) times/case]. Conclusions:Patients can be cured successfully by both acute shortening-lengthening and bone transport techniques. Compared with acute shortening-lengthening group, the complication incidence in antibiotic calcium sulfate-loaded bone transport group was lower, especially, the infection-related complications. Therefore, antibiotic calcium sulfate-loaded bone transport technique has a greater application prospect in patients with large segmental bone defects caused by infection or osteomyelitis.