Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

[Purpose]To analyze the incidence and mortality of oral and pharyngeal cancer in can-cer registration areas of Hunan Province in 2021 and the trend changes from 2012 to 2021.[Methods]Data on oral and pharyngeal cancer incidence and mortality from 2012 to 2021 were collected from 78 quality-controlled cancer registries in Hunan Province,with population data sourced from household registration statistics provided by public security authorities.Indicators such as crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW)in 2021 were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint Regression Program 4.9.0.0 software was used to fit a Log-linear regression model,and the average annual percentage change(AAPC)of ASIRC/ASMRC of oral and pharyngeal cancer from 2012 to 2021 was calculated to analyze the changing trends.[Results]In 2021,the crude incidence rate of oral and pharyngeal cancer in cancer registration areas of Hunan Province was 9.28/105(15.14/105 for males and 3.07/105 for fe-males),with an ASIRC of 6.10/105;the crude mortality rate was 3.75/105(6.19/105 for males and 1.16/105 for females),with an ASMRC of 2.16/105.Both the incidence and mortality rates in male were significantly higher than those in female.Age distribution analysis showed that the incidence rate of oral and pharyngeal cancer increased with age after 30 years old,peaking in the age group of 60～64 years old(22.29/105);the mortality rate continued to rise after 35 years old,reaching the peak in the population aged ≥85 years old(14.52/105).Trend analysis from 2012 to 2021 indicated that the crude incidence rate and ASIRC of oral and pharyngeal cancer increased from 3.50/105 and 2.63/105 in 2012 to 9.28/105 and 6.10/105 in 2021,with AAPC of 12.33％and 10.80％,re-spectively;the crude mortality rate and ASMRC also showed upward trends(AAPC of 9.87％and 7.21％,respectively);all trend changes were statistically significant(all P＜0.05).Sex stratification revealed that the AAPC of ASIRC and ASMRC of oral and pharyngeal cancer in male were higher than those in female(AAPC of ASIRC:12.65％for males vs 4.28％for females;AAPC of ASMRC:8.79％for males vs 4.13％for females).Age-specific trend analysis found that the ASIRC of oral and pharyngeal cancer in the population aged ≤ 44 years old showed an upward trend(AAPC=11.73％,P＜0.001),with the AAPC of male in this group reaching 14.57％;the AAPC of ASIRC for the age groups of 45～64 years old and ≥65 years old were 11.03％and 9.74％,respectively,and the AAPC of ASMRC for these two groups were 10.05％and 8.19％,respectively,with all trend changes being statistically significant(all P＜0.05);there was no statistically significant change in the ASMRC of the population aged ≤44 years old(AAPC=5.66％,P=0.087).[Conclusion]The incidence and mortality rates of oral and pharyngeal cancer in cancer registration areas of Hunan Province remain high and show an upward trend,with a tendency of younger onset.Males and middle-aged and elderly populations are the key focuses of prevention and control.

Objective:To explore the role and molecular mechanisms of S100A6 protein in neonatal meningitis caused by Streptococcus agalactiae. Methods:Human brain microvascular endothelial cells (HBMECs) were used as an in vitro experimental model, and siRNA was employed to construct S100A6 gene knockdown HBMECs strain. The S100A6 gene overexpression cell line was established by lentiviral transfection method. Western blot was used to detect the expression level of S100A6 protein in HBMECs after Streptococcus agalactiae infection, and the change in intracellular inflammatory cytokine protein levels after S100A6 gene knockdown or overexpression. A neonatal bacterial meningitis model was established by injecting Streptococcus agalactiae suspension into the cisterna magna of neonatal Sprague-Dawley (SD) rats. HE staining was used to observe pathological changes in brain tissue; immunohistochemistry was used to detect the expression and distribution of S100A6 protein in brain tissue; Western blot and ELISA were used to measure S100A6 protein levels in cerebrospinal fluid (CSF). Results:Compared with the control group, the intracellular S100A6 protein level in HBMECs increased significantly following Streptococcus cgalactiae infection. After S100A6 gene knockdown, the invasion rate of Streptococcus agalactiae into the HBMECs was significantly reduced ( P<0.01), while intracellular TNF-α and IL-6 protein levels were elevated markedly ( P<0.01). In contrast, overexpression of S100A6 gene increased the invasion rate ( P<0.01) and notably decreased TNF-α and IL-6 protein levels ( P<0.001). In the neonatal SD rat bacterial meningitis model, HE staining revealed substantial neutrophil infiltration in brain tissue after Streptococcus agalactiae infection. Immunohistochemistry showed extensive deposition of S100A6 protein around the meninges, and significant expression of S100A6 protein was also detected in CSF. Conclusions:S100A6 protein is crucial in mediating neonatal meningitis caused by Streptococcus agalactiae infection. S100A6 gene knockdown promotes the production of intracellular inflammatory cytokines and reduces Streptococcus agalactiae invasion into cells, thereby alleviating bacteria-induced cellular damage. Additionally, the increased expression of S100A6 protein in brain tissue and CSF after Streptococcus agalactiae infection suggests its potential as a diagnostic biomarker for bacterial meningitis.

Objective:To investigate the assoication of amino acid metabolism levels with severity of diabetic peripheral neuropathy(DPN) in patients with type 2 diabetes mellitus.Methods:A retrospective analysis was conducted on 118 patients with type 2 diabetes mellitus who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January to April 2021. Patients were divided into groups according to the Toronto Clinical Scoring System(TCSS), and amino acid profiling was performed. General demographics and biochemical indicators of each group were collected to analyze the relationship between DPN severity and amino acid metabolism.Results:As TCSS scores increased, patients were older and had a longer duration of diabetes. Statistically significant differences in leucine, isoleucine, tryptophan, and phenylalanine levels were observed among the four groups. After adjusting for confounding variables using covariance analysis, when the TCSS score was≥13, the serum phenylalanine level was significantly elevated, and the difference was statistically significant( P<0.05). Multivariate linear regression analysis indicated that TCSS score was an influencing factor for phenylalanine levels( P=0.010). Multivariate logistic regression analysis demonstrated that higher serum phenylalanine levels correlated with higher TCSS scores( OR=1.047, 95% CI 1.011-1.083, P=0.010). Receiver operating characteristic(ROC) curve analysis revealed that serum phenylalanine and the difference between phenylalanine and tryptophan had diagnostic value for severe DPN patients, with areas under the ROC curve of 0.673(95% CI 0.553-0.793, P=0.006) and 0.746(95% CI 0.641-0.852, P<0.001) respectively. Conclusions:The levels of phenylalanine and tryptophan in the serum of patients with type 2 diabetes mellitus are correlated with the severity of DPN. These findings suggest that serum phenylalanine, tryptophan, or their metabolic products may be involved in the pathogenesis and progression of DPN.

Objective:To explore the feasibility and effect on the reconstruction of whole hand degloving injury by transfer of nerved tissue flaps in staged surgery.Methods:A retrospective study was conducted on the clinical data of 5 patients who suffered whole hand degloving injury and underwent staged reconstructive surgery with nerved tissue flaps, from December 2018 to December 2022 in the Department of Hand Surgery, Longgang Orthopaedics Hospital of Shenzhen. The patients were 4 males and 1 female, aged 22-45 years. Two of the whole-hand degloved injuries were left hands and 3 of right. Two patients had the whole-hand degloving injury combined with a fracture of distal phalangeal tuberosity, and 1 was complicated with partial rupture of the extensor tendon insertion. Areas of the whole hand degloving injury ranged from 215 cm 2 to 480 cm 2, the size of the hallux nail flaps for reconstruction of thumbs ranged from 54 cm 2 to 104 cm 2, the size of the hallux nail flaps for reconstruction of index fingers ranged from 65 cm 2 to 133 cm 2, and the size of the flaps for reconstruction of all the defects of hands ranged from 119 cm 2 to 255 cm 2. In primary surgery, the thumbs, index fingers and the first webs were reconstructed with bilateral hallux nail flaps to shape the appearance and gain the sensation function. Meanwhile, a single and large defect was created from the defects of hand by bundling up the middle, ring and little fingers together with the all the defects in both palmar and dorsal hand. Then an anterolateral thigh flap (ALTF) was used to have the created single defect wrapped together. Donor sites of the bilateral hallux nail flap were reconstructed with a lobulated ALTF from the other side or with bilateral peroneal artery perforator flaps. Donor sites of the ALTF and peroneal artery perforator flap were pulled and sutured. After the hallux nail flaps and ALTFs of the affected hands had survived and stabilised, multiple staged surgery were then carried out to firstly reconstruct the ring and little fingers, and followed by the middle and ring fingers in turns from the artificial syndactyly created in the primary surgery. In the final stage of surgery, skin of the radial side of middle and ring finger-pulps and the ulnar little finger-pulp were replaced by lateral toe flaps to reconstruct the sensations of the main sensory zones of middle, ring and little finger-pulps. Thereafter, the shape, TPD and finger extension and flexions were observed and evaluated through the postoperative follow-up, at the outpatient clinic according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. The appearance and function of the donor sites in both feet were evaluated with the Maryland foot score. Results:All flaps survived after surgery. Postoperative follow-up lasted up to 14 to 48 months after the last surgery. The appearance of fingers was satisfactory with good function. TPD of thumbs and index finger-pulps had achieved up to 6-8 mm, and 3-8 mm in the main sensory zones of middle, ring and little finger-pulps. TPD in the non-major sensory zones of middle, ring and little finger-pulps was found at 10-14 mm, which scored 13 to 14 and rated as excellent according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. Only a linear scar left in the donor site of thigh. As the appearance of the flaps on the feet was not bloated and there was no obvious abnormality in walking and running, therefore the function of feet scored up to 96 to 97 and rated excellent according to the Maryland foot score.Conclusion:A multi-staged reconstruction of a whole hand degloving injury with nerved tissue flaps not only achieves satisfactory digital and hand appearance, but also with good function. There is no obvious effect on the appearance and function of the donor sites. This surgical strategy is novel in the reconstruction of a whole hand degloving injury.

Objective:To systematically compares the medial plantar venous flap (MPVF) and the lateral toe flap (LTF) reconstruction of digit-pulp defect, aiming to establish whether there exist significant differences between the 2 flaps in flap survival rate, two-point discrimination (TPD), score of Vancouver Scar Scale (VSS) and score of digit-pulp defect reconstruction evaluation.Methods:With a prospective cohort design, this study enrolled 36 patients who were admitted in Department of Hand Surgery, Longgang Eighth People's Hospital of Shenzhen for digit-pulp defects with bone or tendon exposure between January 2024 and September 2024. According to the random grouping method, participants were divided into 2 groups. The MPVF group comprised 18 patients (21 digits) of 13 males (15 digits) and 5 females (6 digits), aged 13-58 (mean 44±12) years. The MPVF group included 9 left and 12 right digits, with distribution as follows: 2 thumbs, 5 index fingers, 7 middle fingers, 5 ring fingers and 2 little fingers. The soft tissue defect area ranged from 2.0 cm × 1.0 cm to 9.2 cm × 3.3 cm (mean 6.69 cm 2± 6.69 cm 2). Flap dimensions ranged from 2.1 cm×1.1 cm to 9.5 cm×3.5 cm (mean 7.54 cm 2±7.22 cm 2). Donor sites were closed primarily or by full-thickness skin grafts harvested from the leg. The LTF group included 18 patients (21 digits) of 15 males (17 digits) and 3 females (4 digits), aged 22-62 (mean 41±12) years. The affected digits in LTF group comprised 12 left and 9 right digits, with a distribution of: 3 thumbs, 9 index fingers, 5 middle fingers, 2 ring fingers and 2 little fingers. The area of soft tissue defect ranges from 1.4 cm × 1.0 cm to 3.9 cm × 1.8 cm (mean 3.93 cm 2± 1.80 cm 2). Flap dimensions ranged from 1.5 cm×1.2 cm to 4.0 cm×1.9 cm (mean 4.52 cm 2±1.89 cm 2). Donor sites were closed primarily, or by full-thickness skin grafts harvested through extension of proximal wound extension or from calf for defect coverage. Patients were contacted for postoperative follow-up by telephone or WeChat to arrange a visit of outpatient clinic or a home visit by surgeon. Statistical analysis was conducted to compare the 2 groups regarding: gender, age and flap dimensions, flap survival rate at 2 weeks after surgery and TPD of flaps, VSS scores, and digit-pulp defect reconstruction evaluation scale scores at 4 months and 6 months postoperatively. P<0.05 indicates a statistically significant difference. Results:The comparative analysis revealed no statistically significant differences between 2 groups in baseline characteristics: gender distribution ( χ2=0.53, P=0.47), mean age ( t=0.75, P=0.46), flap dimensions ( t=1.86, P=0.08), confirming a demographic and surgical parameter equivalence in subsequent outcome comparisons ( P>0.05). All flaps survived at 2 weeks after surgery. All skin grafts at donor sites demonstrated complete viability with uneventful primary wound healing. At 4 months after surgey, the TPD in the MPVF group were 14.71 mm±1.90 mm and 7.81 mm±1.78 mm, respectively, compared to 14.48 mm±1.57 mm and 7.67 mm±1.39 mm in the LTF group at 6 months after surgery. The VSS scores were 1.67±1.11 and 1.29±0.72 for MPVF versus 1.86±1.15 and 1.38±0.81 for LTF at corresponding time points. The digit-pulp defects reconstruction evaluation scale scores showed 88.43±2.62 and 91.43±3.59 for MPVF versus 88.19±2.70 and 91.19±3.50 for LTF. Statistical analysis revealed no significant differences (all P>0.05) at 2 postoperative time points. Conclusion:The MPVF demonstrated non-inferior clinical efficacy to the LTF in reconstruction of digit-pulp defects, with comparable outcomes in flap survival rate at 2 weeks, and in TPD, VSS scores, digit-pulp defect reconstruction evaluation scale scores at 4 months and at 6 month after surgey.

This study investigates the expression pattern and functional significance of EF-hand domain-containing protein 2 (EFHD2) in hepatocellular carcinoma (HCC), with particular focus on its regulatory effects on tumor proliferation, migration, and invasion. Cellular experimental study was completed from June 2024 to January 2025 in the Basic Laboratory of the General Hospital of Southern Theater Command. TCGA database to determine EFHD2 expression and its clinicopathological correlations. GSCA database to assess methylation patterns and immune infiltration. Model of transient overexpression and knockdown of EFHD2 was constructed in hepatocellular carcinoma cells Hep3B, then RT-qPCR and Western blot were applied to verify the transfection efficiency. CCK-8 and colony formation assays for proliferation assessment, Transwell chambers for migration/invasion quantification. Protein-protein interaction networks were constructed via STRING, followed by GO/KEGG enrichment analysis. Statistical analysis was performed using the two independent samples t-test. The results showed that EFHD2 demonstrated significant upregulation in HCC tissues versus normal controls ( P<0.05). Elevated EFHD2 expression correlated with advanced clinical stage ( P<0.05) and poor differentiation ( P<0.05). In the CCK-8 assay, the EFHD2 overexpression group demonstrated significantly higher cell viability than the control group, as evidenced by 450 nm relative absorbance values on Day 1 (0.529±0.019 vs. 0.515±0.016, F=0.041, P=0.320), Day 2 (1.356±0.019 vs. 1.094±0.042, F=3.833, P<0.001), Day 3 (2.817±0.049 vs. 2.143±0.124, F=3.833, P<0.001), and Day 4 (3.848±0.015 vs. 3.430±0.021, F=0.469, P<0.001). The EFHD2 knockdown group showed reduced cell viability compared to controls: Day 1 (0.541±0.020 vs. 0.552±0.015, F=0.098, P=0.423), Day 2 (1.154±0.009 vs. 1.326±0.029, F=2.485, P<0.001), Day 3 (2.453±0.041 vs. 2.653±0.031, F=0.479, P<0.001), and Day 4 (3.685±0.038 vs. 3.836±0.021, F=6.804, P<0.001). In colony formation assays, the overexpression group displayed a significant increase in colony numbers (254.667±23.861 vs. 186.000±16.703, F=0.865, P=0.015), whereas the knockdown group exhibited decreased colony formation (229.000±24.637 vs. 306.667±36.501, F=0.988, P=0.038). In Transwell assays, the EFHD2 overexpression group revealed enhanced migratory capacity [ (605.000±72.670) cells vs. (472.667±28.095) cells, F=2.462, P=0.042] and invasive potential [(767.333±21.221) cells vs. (414.333±16.623) cells, F=0.331, P<0.001]. The knockdown group showed attenuated migration [(311.000±71.084) cells vs. (479.667±50.846) cells, F=0.718, P=0.029] and invasion [(247.667±48.263) cells vs. (345.667±32.130) cells, F=0.727, P=0.043] compared to controls. The network of EFHD2-interacting proteins was further constructed by the STRING database, and the GO and KEGG analysis were used to perform bioinformatics analysis reveal that EFHD2 is mainly involved in actin cytoskeleton regulation. In conclusion, EFHD2 is highly expressed in HCC and is involved in the process of proliferation, migration and invasion of HCC.