OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Objective:To scientifically measure and morphologically evaluate the anatomical shape of the skin in the first web space based on cadavers, and to guide the design of flap in this area.Methods:Sixteen human cadavers fixed with 10% formaldehyde without injury or deformity on the hand were selected in the Department of Hand Surgery, the Third Hospital of Suqian. According to the characteristics of the first web area, marker points were selected for measurement and morphological observation. Morphological characteristics of the first web with thumb radial abduction(r) or palmar abduction(p) were measured and compared. The t-test was used for statistical analysis. P<0.05 was considered statistically significant. According to the results of measurement, standardised shapes and parameters of the skin were obtained for flap repair of defect of the first web. Results:When the thumb was in palmar abduction, the maximum distance [a(p)] of the first web of female(F) and male(M) was 5.78/8.42 cm(F/M), and the skin [S(p)] was 17.09/23.63 cm 2(F/M), both were significantly greater than the distance [a(r)] at 4.86/6.28 cm and the area of skin area [S(r)] at 14.39/20.15 cm 2 when thumb was in the radial abduction position( P<0.05). There was no significant difference in the length of [b(r)] and [b(p)] alone the long axis of flap between palmar and radial abductions(7.54/9.38 cm and 7.34/9.74 cm, respectively) of the thumb( P>0.05). It was found that the area of first web was not shaped as a symmetrical spindle, but an irregular quadrilateral inclined to the index finger. Conclusion:Design and measurement of a flap for the first web space should take the maximum palmar abduction of a thumb as a reference. The asymmetric quadrilateral flap design is more in line with the anatomical and characteristics in the region.

Currently, the total ureteral avulsion are mainly secondary to ureteroscopy, and it is rarely caused by uterine evacuation clinically. This paper reported a case of total ureter avulsion after uterine evacuation, treating by ileal replacement for ureter under general anesthesia, and the surgical outcome was good. Uterine evacuation is a routine, less risky procedure, but it also can lead to serious complications such as total ureteral avulsion or bladder rupture. For potential high-risk patients with uterine evacuation, preventive measures such as accurate localization under B-ultrasound guidance or pre-operative ureteral stents indwelling are useful to avoid the occurrence of such serious complications. If total ureteral avulsion occurs, ileal replacement for ureter is a viable and effective treatment.

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.

Objective:To investigate the risk factors of bone cement leakage and recompression of injured vertebrae after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A case-control study was performed to analyze the clinical data of 297 patients with single-segment OVCF who underwent PKP in First Affiliated Hospital of Soochow University from January 2017 to January 2021, including 67 males and 230 females; aged 60-92 years [(69.5±8.2)years]. According to the occurrence of bone cement leakage, the patients were divided into leakage group ( n=36) and no leakage group ( n=261). According to the occurrence of recompression of injured vertebrae, the patients were divided into recollapse group ( n=40) and no recollapse group ( n=257). The gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement injection volume, bone cement distribution, and postoperative anti-osteoporosis treatment were recorded. Univariate analysis was used to analyze the correlation of those factors with bone cement leakage and recompression of injured vertebrae after PKP, followed by multivariate Logistic regression analysis to identify the independent risk factors. Results:Univariate analysis showed that fracture severity, cortical disruption and bone cement injection volume were related to bone cement leakage ( P<0.05 or 0.01). Gender, age, fracture segment, type of fracture, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement distribution, and postoperative anti-osteoporosis treatment were not related to bone cement leakage (all P>0.05). Univariate analysis showed that intravertebral cleft, bone cement distribution, and postoperative anti-osteoporosis treatment were associated with recompression of injured vertebrae (all P<0.01). Gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, and bone cement injection volume were not related to recompression of injured vertebrae (all P>0.05). Multivariate Logistic regression analysis showed that severe fracture ( OR=4.23, 95% CI 1.52-11.81, P<0.01), cortical disruption ( OR=3.29,95% CI 1.52-7.13, P<0.01), and bone cement injection volume >8 ml ( OR=2.31,95% CI 1.09-4.92, P<0.05) were significantly related to bone cement leakage. Multivariate Logistic regression analysis showed that intravertebral cleft ( OR=2.10, 95% CI 1.03-4.30, P<0.05), solid type of bone cement distribution ( OR=2.56, 95% CI 1.25-5.27, P<0.05) and no anti-osteoporosis treatment after operation ( OR=3.06, 95% CI 1.46-6.40, P<0.01) were significantly related to recompression of injured vertebrae. Conclusions:For OVCF patients, severe fracture, cortical disruption, and bone cement injection volume>8 ml are independent risk factors for bone cement leakage after PKP. Intravertebral cleft, solid type of bone cement distribution, and no anti-osteoporosis treatment after operation are independent risk factors for recompression of injured vertebrae after PKP.

Objective:To investigate the clinical effect of the relaying perforator flap for repairing the donor site of the anterolateral thigh flap.Methods:From March 2019 to June 2020, 28 consecutive patients who underwent anterolateral thigh free flap reconstruction for limb soft tissue defects were retrospectively reviewed. A relaying perforator flap was selected from one of the four areas adjacent to the donor site of the anterolateral thigh flap for covering the donor site of the anterolateral thigh flap. The secondary donor site was closed directly. The followed-up contents included the appearance and texture of the flaps. The postoperative followed-up was performed through outpatient visits, telephone, and WeChat interviews.Results:A total of 28 patients were included, with an average age of 37.3 (ranging from 15 to 65). The relaying perforator flap was selected from the anteromedial thigh region ( n=13), the proximal anterolateral thigh region( n=6), the distal anterolateral thigh region ( n=5), and the ilioinguinal region ( n=4). The size of the anterolateral thigh flap ranged from 12.0 cm×10.0 cm to 20.0 cm×13.0 cm, and the size of the relaying perforator flap ranged from 6.0 cm×5.0 cm to 11.0 cm×7.5 cm. The followed-up time ranged from 1 to 6 months (mean 4.8 months). The color, texture, and contour of the flaps were good. Only one linear scar is left in the donor site. Two cases with small necrosis (1.0 cm×2.0 cm and 1.5 cm×1.5 cm, respectively) were found in the distal edge of relaying perforator flaps. Conclusions:The relaying perforator flap is considered as an optimized and reliable method for repairing the donor site of an anterolateral thigh flap and should be recommended.

Objective:To investigate the clinical effect of the relaying perforator flap for repairing the donor site of the anterolateral thigh flap.Methods:From March 2019 to June 2020, 28 consecutive patients who underwent anterolateral thigh free flap reconstruction for limb soft tissue defects were retrospectively reviewed. A relaying perforator flap was selected from one of the four areas adjacent to the donor site of the anterolateral thigh flap for covering the donor site of the anterolateral thigh flap. The secondary donor site was closed directly. The followed-up contents included the appearance and texture of the flaps. The postoperative followed-up was performed through outpatient visits, telephone, and WeChat interviews.Results:A total of 28 patients were included, with an average age of 37.3 (ranging from 15 to 65). The relaying perforator flap was selected from the anteromedial thigh region ( n=13), the proximal anterolateral thigh region( n=6), the distal anterolateral thigh region ( n=5), and the ilioinguinal region ( n=4). The size of the anterolateral thigh flap ranged from 12.0 cm×10.0 cm to 20.0 cm×13.0 cm, and the size of the relaying perforator flap ranged from 6.0 cm×5.0 cm to 11.0 cm×7.5 cm. The followed-up time ranged from 1 to 6 months (mean 4.8 months). The color, texture, and contour of the flaps were good. Only one linear scar is left in the donor site. Two cases with small necrosis (1.0 cm×2.0 cm and 1.5 cm×1.5 cm, respectively) were found in the distal edge of relaying perforator flaps. Conclusions:The relaying perforator flap is considered as an optimized and reliable method for repairing the donor site of an anterolateral thigh flap and should be recommended.

Objective:To evaluate the clinical effect of the modified transfer of the proximal interphalangeal joint (PIPJ) from the second toe in the treatment of a finger PIPJ defect.Methods:A total of 13 patients with finger PIPJ defects caused by traumatic injury were enrolled from May, 2017 to March, 2020. All the PIPJ defects had primary traumatic repairs. The causes of injury: 5 patients were caused by strangulation, 4 by chainsaw, 2 by strangulation and 2 by crushing. Of which, 7 patients had index finger injury, 3 middle fingers and 3 ring fingers. The operations were carried out 3-7 months after the first stage of treatment. The grafting of the PIPJ of the second toe with modified vascular anastomosis were performed. The ipsilateral second toe was taken in 10 patients, and the contralateral second toe in 3 patients. The grafted joints all carried observation skin islands, with an area of 1.0 cm×1.5 cm-1.0 cm×2.0 cm. All the secondary bone defects in the donor site of the toe were reconstructed with iliac bone grafts, and the length of the iliac bone strips was 4.0-6.0 cm. At the same time, the island flap on the fibular side of the great toe was removed and repaired at the donor site, with an area of 1.1 cm×1.6 cm - 1.1 cm×2.1 cm. Early postoperative rehabilitation was performed. The patients were followed-up through outpatient visits, telephone and WeChat interviews.Results:All the 13 finger PIPJ and donor site island flaps survived. Bone healing were observed in all patients with the healing time in 8-12(average 10) weeks. Three patients with severe adhesion of joint and tendon were treated with secondary release. All the patients were followed-up for 10 - 18 months without degeneration of PIPJ. Active range of motion of PIPJ ranged: 45°-90° in flexion and 0°-10° in extension, the average motion activity was 66.3°. Seven patients were in excellent, 4 in good and 2 in fair, according to the function assessment proposed by the Society of Hand Surgery of Chinese Medical Association. The appearance on donor site was good and the walking was normal in the longterm follow-up. Only one linear scar was left in the ilioinguinal donor site without obvious discomfort.Conclusion:It was possible to use the modified transfer of the PIPJ from the second toe in the treatment of a finger PIPJ defect. An iliac bone graft and an island flap of the first toe transfer can preserve the appearance and function of the toes.

OBJECTIVE：To evaluate th e effectiveness ，safety and economy of albu min-bound paclitaxel （nab-PTX）in the treatment of breast cancer by using rapid health technology assessment （HTA），and to provide evidence-based reference for drug selection. METHODS ：Retrieved from PubMed ，the Cochrane Library ，CNKI，Wangfang database and other databases ，systematic evaluation/Meta-analysis，HTA and pharmacoeconomic studies about nab-PTX in the treatment of breast cancer were included ；the conclusions were classified and analyzed by using descriptive analysis. RESULTS ：A total of 5 systematic reviews/Meta-analysis ， 8 pharmacoeconomic studies were included in this study. Compared with conventional taxanes ，nab-PTX increased pathological complete response （pCR）rate [OR ＝1.39，95％CI（1.16，1.67），P＜0.001] and event-free survival （EFS）[HR＝0.69，95％CI（0.57， 0.85），P＜0.001] in neoadjuvant chemotherapy （NAC）-treated breast cancer patients. However ，there were no significant differences in overall survival （OS），progression-free survival （PFS），objective response rate （ORR）and disease control rate （DCR）in metastatic breast cancer （MBC）patients between 2 groups. In the terms of safety ，nab-PTX increased the incidence of grade 3-4 sensory neuropathy [OR ＝1.89，95％CI（1.36，2.61），P＜0.001] in MBC patients ，and increased the incidence of neutropenia [OR ＝ 1.52，95％CI（1.23，1.88，P＜0.001]，sensory neuropathy [OR ＝ 2.17，95％CI（1.38，3.40），P＜0.001]，rash [OR ＝1.46，95％CI mei1213@163.com （1.18，1.80），P＜0.001] and fatigue [OR ＝1.28，95％CI（1.04， 1.56）， P＝0.02] in NAC -treated breast cancer patients.Pharmacoeconomic studies showed that nab-PTX could improve the quality adjusted lif e years of MBC patients compared with traditional taxanes ，and it was a economical option. CONCLUSIONS：Nab-PTX enhances pCR in NAC-treated breast cancer patients ，but has no significant advantage in the effectiveness of MBC patients ，and increases the occurrence of ADR. Nab-PTX may have a cost-utility advantage over conventional taxanes for MBC.