OBJECTIVE: To investigate the clinical efficacy of lengthened proximal femoral nail antirotation (PFNA) and InterTan in the treatment of subtrochanteric femur fractures in the elderly. METHODS: A retrospective analysis was performed on the data of 65 elderly patients diagnosed with subtrochanteric femoral fractures who met the inclusion criteria between October 2016 and January 2022. The enrolled patients were categorized into two groups according to the type of internal fixation used: the lengthened proximal femoral nail antirotation(PFNA) group and the InterTan group. There were 32 patients in the PFNA group, comprising 20 males and 12 females, with ages ranging from 60 to 85 years old with an average of (69.3±6.7 ) years old. Among these patients, 15 patients resulted from traffic accidents and 17 patients were caused by falls. According to the Seinsheimer classification system, there were 11 patients as type Ⅱ, 14 patients as type Ⅲ, 6 patients as type Ⅳ, and 1 patient as type Ⅴ. The InterTan group comprised 33 patients, including 20 males and 13 females, aged from 60 to 85 years old with an average of (69.8±7.8 ) years old. Of these, 15 patients resulted from traffic accidents, while 18 patients were caused by falls. According to the Seinsheimer classification system, 10 patients as type Ⅱ, 15 patients as type Ⅲ, 7 patients as type Ⅳ, and 1 patient as type Ⅴ. The intraoperative blood loss, operative duration, and fracture healing time were recorded and compared between two groups. The quality of fracture reduction was assessed using Chang's criteria. Additionally, the Harris hip score was utilized to evaluate hip function in both groups at 3 months postoperatively and at the final follow-up. RESULTS: All patients were followed up for a period ranging from 10 to 20 months with an average of (14.6±4.5) months. No statistically significant differences were observed between two groups in terms of operation time, intraoperative blood loss, quality of fracture reduction, or reduction methods (P>0.05). Three months after the surgery, the Harris hip score in the InterTan group was 80.0(78.0, 83.5) points, which was significantly higher than that in the PFNA group, which recorded a score of 77.5(75.0, 81.8) points. This difference was statistically significant (P<0.05). At the final follow-up, the Harris hip score in the InterTan group was 80.0(76.5, 87.0), while that in the PFNA group was 78.0(74.3, 82.8). No statistically significant difference was observed between two groups (P>0.05). CONCLUSION The use of lengthened PFNA and InterTan in the treatment of elderly subtrochanteric femur fractures can both achieve good treatment results, with the advantages of simple operation, firm fixation, and low failure rate of internal fixation. The lengthened InterTan can achieve better hip function than PFNA.
Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Bone Nails ; Retrospective Studies ; Hip Fractures/surgery* ; Middle Aged ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Fixation, Internal/methods* ; Femoral Fractures/surgery*

ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of moxifloxacin in Chinese healthy adult subjects.Methods A single-center,randomized,open,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of moxifloxacin tablets 0.4 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of moxifloxacin in plasma were determined by liquid chromatography-tandem mass spectrometry.Results The main pharmacokinetic parameters of moxifloxacin in fasting state and high-fat diet states were as follows:Cmax were(2 286.09±802.64)and(1 963.33±474.99)ng·mL-1;t1/2 were(12.32±1.42)and(13.56±1.38)h;AUC0-twere(2.70±0.51)×104 and(2.60±0.55)×104 ng·mL-1·h;AUC0-∞ were(2.88±0.54)×104 and(2.85±0.63)×104 ng·mL-1·h;tmax were 1.50 and 2.00 h.After high-fat diet,the AUC was not significantly changed,Cmax was decreased by 14.12％,and tmax was indistinctively delayed(all P＞0.05).Conclusion Food had no effects on the absorption rate and degree of moxifloxacin.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals. METHODS: Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated. RESULTS: SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. CONCLUSION s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
Humans ; COVID-19 Vaccines/therapeutic use* ; COVID-19 ; SARS-CoV-2 ; Killer Cells, Natural ; HIV Infections ; Antibodies, Viral

OBJECTIVE: To investigate the changes in serum levels of endothelin-1 (ET-1) and connective tissue growth factor (CTGF) in patients with atrial fibrillation (AF) and their value for predicting recurrence of AF after radiofrequency ablation (RFCA). METHODS: Sixty-six patients with paroxysmal AF (PaAF) and 72 with persistent AF (PaAF) admitted in our hospital were recruited as AF group and 80 patients with sinus rhythm as the control group, and in all the participants, serum levels of ET-1 and CTGF were measured using ELISA and Western blotting. From 6 patients with AF and 6 with sinus rhythm undergoing cardiac surgery in our hospital, tissue samples of the right atrial appendage were taken intraoperatively for observation of structural changes of the cardiomyocytes, myocardial fibrosis and expression of ET-1 and CTGF protein. In AF group, the patients receiving RFCA were followed up for 6 months following the procedure for assessment of the outcomes. RESULTS: Compared with the control patients, the patients with AF showed obvious damages of the cardiomyocyte structure and myocardial fibrosis. Serum levels of ET-1 and CTGF levels were significantly higher in PaAF and PeAF groups than in the control group, and were higher in PeAF group than in PaAF group. In the patients with AF, serum ET-1 and CTGF levels were positively correlated with left atrial diameter (LAD) (P < 0.05), and ET-1 was positively correlated with CTGF levels (P < 0.05). In patients with postoperative AF recurrence, the serum levels of ET-1 and CTGF were significantly higher than those in patients without recurrence; serum ET-1 and CTGF levels before and after the operation were positively correlated with the recurrence of PeAF, and elevated serum levels of ET- 1 and CTGF were identified by logistic regression analysis as independent risk factors for postoperative recurrence of PeAF. CONCLUSION Serum levels of ET-1 and CTGF are significantly elevated in AF patients in positive correlation with AF duration. ET-1 and CTGF levels are higher in AF patients with postoperative recurrence, and they both have predictive value for recurrence of PeAF following RFCA.
Humans ; Atrial Fibrillation ; Endothelin-1 ; Connective Tissue Growth Factor ; Chronic Disease ; Atrial Appendage ; Fibrosis

Objective:To investigate the efficacy of a novel self-designed skin-stretching device for skin-soft tissue defects and bone exposure after internal fixation of calcaneal fracture.Methods:From July 2018 to January 2021, 9 patients were treated at Orthopedic Hospital, Southeast Hospital Affiliated to Xiamen University for skin-soft tissue defects and bone exposure after internal fixation of calcaneal fracture. They were 6 males and 3 females, aged from 19 to 61 years (mean, 42.6 years). The interval between their initial internal fixation and the present operation ranged from 14 to 75 days (average, 47.3 days). Of them, one developed wound dehiscence due to fat liquefaction, 2 necrosis of skin and soft tissue along the wound edges, and 6 incision infection. Their fusiform skin and soft tissue defects had formed after routine expansion of the wound, with an area of 5.0 cm×2.0 cm to 7.0 cm×3.5 cm, and all their wounds were positive by Pinch test. After a Kirschner wire with a diameter of 2.0 was placed on both sides of the wound, our novel self-designed skin-stretching device was installed. Intraoperatively, depending on the soft tissue conditions on both sides, the wound was closed acutely by about 5 mm in width. The threaded rod of the skin-stretching device was adjusted every day after operation to gradually reduce the wound surface until the wound edge was closed and sutured without tension. During wound stretch, the visual analogue scale (VAS), wound approaching time, stretch speed, wound healing time, complications and the Vancouver Scar Scale (VSS) for the wound scar at the last follow-up were recorded.Results:All the 9 patients were followed up for 8 to 18 months (average, 12.5 months). The wounds were successfully closed in all the patients. The time for wound closure (till the suture) ranged from 8 to 15 d, averaging 12.1 d; the stretch rate from 1 to 3 mm/d, averaging 2 mm/d; the time for complete wound healing (to the suture removal) from 22 to 30 d, averaging 26.8 d; the VAS score during the stretch from 3 to 7 points, averaging 4.9 points; the VSS score from 2 to 7 points, averaging 4.1 points. There was no recurrence of surgical site infection, skin re-necrosis or reoperation in the patients.Conclusions:In the treatment of skin-soft tissue defects and bone exposure caused by various reasons after internal fixation of calcaneal fracture, our novel self-designed skin-stretching device is an effective in situ wound repair instrument, showing advantages of simple operation, less trauma and high safety. It is suggested that the stretch speed should average 2 mm/d, which is well tolerated by patients.

Objective To investigate the effects of dexmedetomidine (DEX) on the nuclear factor-KB inhibitor protein kinase (IKK)/nuclear factor-KB inhibitor protein a (IKB(X)/nuclear factor-KB (N F - K B) pathway and cognitive dysfunction in rats with post-traumatic stress disorder (PTSD) . Methods Rats were randomly divided into control group, model group, positive group and DEX group. Except for the control group, the PTSD model was constructed by single prolonged stress method (SPS), and the corresponding drugs were given after the completion the model. Open field test and Morris water maze method were used to detect the autonomous activity, learning and memory ability of rats; HE staining was used to observe the morphological characteristics of cerebral cortex and hippocampus; ELISA and Western blotting were used to detect the contents of interleukin (IL)-1(3, IL-6, tumor necrosis factor a (TNF-a) and the expression levels of IKK, IKB(X, purinergic ligand-gated ion channel 7 receptor (P2X7R), leucine-rich repeat domain protein 3(NALP3) in hippocampus; the NF-KB activity was assessed by electrophoretic mobility shift assay (EMSA). Results Compared with the control group, the cerebral cortex and hippocampal CA1 region of model group were in structural disorders, nuclear pyysis and other pathological changes happend, learning and memory ability of rats decreased (P < 0. 05), contents of IL-lp, IL-6 and TNF-a, expression levels of IKK, IKB(X, P2X7R and NALP3, NF-KB activity in hippocampus increased (P<0. 05); Compared with the model group, the pathological phenomena in cerebral cortex and hippocampal CA1 area of rats in positive group and DEX group were in alleviated, and the changes of the above indexes were opposite to those of model group (P<0. 05) . Conclusion DEX can significantly improve the autonomous activity ability and learning and memory ability in PTSD rats, reduce inflammatory reaction in hippocampus and improve cognitive dysfunction, which may be related to the down-regulation of IKK/TKBQ!/NF-KB pathway.

To evaluate the value of endoscopic retrograde cholangiopancreatography(ERCP)and SpyGlass in the diagnosis of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). Data of patients who underwent ERCP and SpyGlass in Hangzhou First People′s Hospital from January 2016 to December 2019 were analyzed. ERCP and SpyGlass features, complications, clinicopathologic characteristics and prognosis were retrospectively analyzed.A total of 9 patients (5 benign lesions and 4 malignant lesions) were included.ERCP was successfully performed in 9 cases, while SpyGlass was technically successful in 8 cases. Endoscopy showed mucus outflow from the papilla in 5 cases, and the mucus was removed by the balloon of ERCP in 8 cases.ERCP showed bile duct diffuse dilatation and filling defects in all patients. SpyGlass found the mucus in the bile duct in all patients. SpyGlass showed lesion mucosa were fish-egg like without vascular images (Ⅱtype, 3 cases), fish-egg like with vascular images (Ⅲ type, 1 case), villous (Ⅳtype, 4 cases). SpyGlass defined extent of the lesion in 8 cases. SpyGlass found that the lesion involved the intra and extrahepatic bile ducts in one case. Therefore, liver transplantation was recommended to avoid surgical exploration. One type Ⅲ lesion underwent a direct biopsy. The pathology showed moderate dysplasia, which was consistent with the postoperative pathology. No complication occurred. ERCP combined with SpyGlass could clarify the scope of IPMN-B and provide basis for surgical options, which is safe and effective in IPMN-B diagnosis.