Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P＜0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P＜0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P＜0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P＜0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.

Objective:To investigate the effects of ATG5 and ATG7 genes on the sensitivity of multiple myeloma(MM)cell line RPMI-8226 cells to ferroptosis.Methods:CRISPR/Cas9 technology was used to knock out the autophagy key genes ATG5 and ATG7 in RPMI-8226 cells.Western blot was used to identify gene knockout cells,and detect the expression changes of autophagy-related proteins P62 and LC3B.Flow cytometry was used to detect the change of sensitivity of gene knockout cells to RSL3.The content of intracellular ferrous ions and reactive oxygen species(ROS)level in gene knockout cells were detected.Results:Western blot result confirmed that ATG5 and ATG7 genes were knocked out successfully in RPMI-8226 cells.The result of flow cytometry showed that the cell viability of RPMI-8226 cells was dose-dependent on different concentrations of RSL3(r=-0.969).RSL3(10 μmol/L)was used to induce ferroptosis in cells of control group and gene knockout groups,then the cell viability in gene knockout groups were both higher than control group after 48 hours(both P＜0.001).After knocking out the ATG5 and ATG7 genes,the content of intracellular Fe2+decreased significantly compared with control group(both P＜0.01),and the ROS level also decreased(both P＜0.001).Conclusion:Knockout of ATG5 and ATG7 genes can inhibit the ferroptosis of MM cells,and LAP pathway may be involved in the regulation.

Objective:To explore whether Ph+acute lymphoblastic leukemia (ALL)cell line SUP-B15 treated with imatinib occurs a tolerant status charactered by cell proliferation suppression but apoptotic resistance,then evaluate whether IGF1-R inhibitor AEW541 can break this tolerance,and further explain its mechanisms.Methods:SUP-B15 cells were treated with different concentrations of imatinib or AEW541.Cell proliferation was assayed by Deep Blue,and apoptotic cells were determined by Annexin V/7-AAD staining.Apoptotic rate was measured by flow cytometry after co-treatment of imatinib and AEW541.Western blot was used to evaluate ABL downstream signals,including the phosphorylation of STAT5,ERK1/2,and AKT,as well as to detect cleaved caspase-3 and PARP1,the molecular signatures of apoptosis.Furthermore,an inhibitor of STAT5 or MEK-ERK1/2 was used to confirm the key mechanism of the combination of imatinib and AEW541 induced SUP-B15 cell apoptosis.Results:Imatinib monotherapy effectively suppressed the proliferation of SUP-B15 cells,but did not induce significant increase of apoptotic rate,leading to occurrence of tolerant status.AEW541 monotherapy did not dramatically affect the proliferation and apoptosis of SUP-B15 cells,but significantly increased apoptotic rate of SUP-B15 cells and cleavage of caspase-3 and PARP1 when combined with imatinib simultaneously. A combination of imatinib and AEW541 reduced STAT5 and ERK1/2 phosphorylation as compared with imatinib monotherapy in SUP-B15 cells,but had no impact on AKT phosphorylation.Apoptosis could be induced by STAT5 inhibitor AC-4-130,but not by MEK-ERK1/2 inhibitor trametinib in SUP-B15 cells.Conclusion:SUP-B15 cells treated with imatinib can establish drug tolerance.IGF1-R inhibitor AEW541 can further reduce STAT5 activation,thereby boosting the effect of apoptotic induction of imatinib on SUP-B15 cells.This research may provide a new idear to overcome imatinib tolerance.

Objective:To analyze the application of direct cochlear nerve monitoring technology-cochlear nerve action potential (CNAP) monitoring in resection of vestibular schwannoma (VS) and to compare with which in microvascular decompression (MVD) of hemifacial spasm (HFS), in order to provide reference for identification of the cochlear nerve during VS resection surgery and predicting postoperative hearing preservation.Methods:From June 2018 to March 2022, patients with facial spasm and vestibular schwannoma who underwent retrosigmoid approach surgery at the Chinese PLA General Hospital were collected. Before surgery, there were a total of 11 HFS patients and 30 VS patients. Before surgery, the former had hearing level of class A(AAO-HNS), while the latter had serviceable hearing (AAO-HNS class A-B), with a maximum tumor diameter of≤20 mm. CNAP combined with Auditory Brainstem Response (ABR) monitoring was performed during surgery. SPSS 23.0 software was used to analyze the differences of ABR and CNAP parameters between the two groups.Results:The preoperative ABR test in the VS group showed that the latency of wave V and I-V interval were significantly prolonged compared to the HFS group ( t=8.36, P<0.001; t=4.61, P<0.001).In VS group, all tumors were totally removed with preserved facial nerve function (House-Brackmann grade Ⅰ-Ⅱ). The serviceable hearing preservation rate was 63.3%. In the HFS group, the initial CNAP waveforms were triphasic and biphasic, with N1 wave latency of (4.32±0.37) ms and amplitude of 25.20 [15.63, 35.40]μV. The distribution of CNAP waveforms before tumor resection in the VS group was the same as that in the HFS group, and which in the hearing preservation group after surgery was also the same. Compared with the HFS group, the latency of N1 wave was prolonged ( t=2.670, P=0.011; t=4.584, P<0.001), and the amplitude of N1 wavein the VS group before tumor resection was lower ( Z=-3.001, P=0.003). The amplitude of N1 wave in the hearing preservation group after surgery was 20.20 [6.23, 40.90] μV,which was significantly higher than that before tumor resection ( Z=-2.133, P=0.033), but there was no statistically significant difference compared to the HFS group ( Z=-0.495, P=0.621). Conclusions:The reference range of CNAP in normal hearing population can be preliminarily obtained by the analysis of CNAP in MVD surgery. The latency of N1 wave in VS patients is prolonged and the amplitude of N1 wave is decreased due to tumor compression. The CNAP waveform combined with the change of N1 wave amplitude can provide reference for intraoperative mapping of the cochlear nerve and prediction of postoperative hearing preservation.

Objective: To investigate the efficacy and safety of pedunculated rectus abdominis combined with bilateral ureteral extravestheter drainage in the treatment of refractory bladder-vaginal stump fistula. Methods: The clinical data of 8 cases of the refractory bladder-vaginal stump fistula were admitted to the Second Hospital of Hebei Medical University and Henan Cancer Hospital and underwent the clinical treatment of bladder-vaginal stump from December 2019 to December 2022 were collected. The reason of refractory bladder-vaginal stump fistula was analyzed, the operation manner of pedunculated rectus abdominis combined with peduncle and bilateral ureter for the treatment of bladder-vaginal stump through extrabladder drainage was explored. The operation time, bleeding volume and clinical effect were record. Results: The median operation time of 8 patients was 150 minutes(120~180 min), and the median blood loss was 400 ml(200~600 ml). During the perioperative period, there were 2 cases of incision infection, delayed healing by debridement and dressing, 2 cases of incision rupture and suture wound healing after reoperation, and 2 cases of urinary tract infection were cured by anti-infection. When followed up for 6 months, 8 cases of vesicovaginal stump fistula were cured. Conclusion: Bilateral ureteral external drainage of the rectus abdominis muscle, has a practical effect in the treatment of refractory bladder-vaginal stump fistula, which can be one of the clinical repairing treatment.
Female ; Humans ; Urinary Bladder/surgery* ; Ureter/surgery* ; Rectus Abdominis ; Drainage ; Fistula

Objective: To investigate the efficacy and safety of pedunculated rectus abdominis combined with bilateral ureteral extravestheter drainage in the treatment of refractory bladder-vaginal stump fistula. Methods: The clinical data of 8 cases of the refractory bladder-vaginal stump fistula were admitted to the Second Hospital of Hebei Medical University and Henan Cancer Hospital and underwent the clinical treatment of bladder-vaginal stump from December 2019 to December 2022 were collected. The reason of refractory bladder-vaginal stump fistula was analyzed, the operation manner of pedunculated rectus abdominis combined with peduncle and bilateral ureter for the treatment of bladder-vaginal stump through extrabladder drainage was explored. The operation time, bleeding volume and clinical effect were record. Results: The median operation time of 8 patients was 150 minutes(120~180 min), and the median blood loss was 400 ml(200~600 ml). During the perioperative period, there were 2 cases of incision infection, delayed healing by debridement and dressing, 2 cases of incision rupture and suture wound healing after reoperation, and 2 cases of urinary tract infection were cured by anti-infection. When followed up for 6 months, 8 cases of vesicovaginal stump fistula were cured. Conclusion: Bilateral ureteral external drainage of the rectus abdominis muscle, has a practical effect in the treatment of refractory bladder-vaginal stump fistula, which can be one of the clinical repairing treatment.
Female ; Humans ; Urinary Bladder/surgery* ; Ureter/surgery* ; Rectus Abdominis ; Drainage ; Fistula

Drug repositioning provides new clinical indications for existing drugs. The imbalance between body's "immune-inflammation" regulation is one of the important factors in the occurrence and development of diabetic nephropathy (DN). Chinese patent medicine Kunxian capsule is clinically used for treating rheumatoid arthritis with satisfying immune-modulatory and anti-inflammatory actions. Notably, accumulating clinical evidence based on small cohorts had shown that Kunxian capsule may be used to treat DN. But the underlying pharmacological mechanisms remain unclear. Therefore, this study integrated "drug target-disease gene-biological pathway-function module" multi-level associated network analysis, and in vivo and in vitro experiments, to verify the pharmacological effects of Kunxian capsules in DN and to elucidate its molecular mechanisms. The experimental protocol was reviewed by the Laboratory Animal Welfare and Ethics Committee of China Academy of Chinese Medical Sciences, and it complies with the relevant regulations on laboratory animal welfare and ethics. As a result, the network analysis showed that the candidate targets of Kunxian capsule against DN were significantly involved into various functional modules which were related to modulation of immune-inflammation system, basement membrane lesion, abnormal hemorheology, energy metabolism and hormone metabolism, and the number of targets enriched by PI3K/AKT/NF-κB pathway is the largest. In addition, both in vivo and in vitro experiments demonstrated that Kunxian capsule by gavage effectively reduced blood glucose, improved insulin resistance, reduced blood lipid, inhibited renal extracellular matrix protein production and renal inflammation, improved renal function and pathological damages, and inhibited the activity of PI3K/AKT/NF-κB/TNF-α/IL-1β pathway in diabetic nephropathy rats. Collectively, these findings suggest the therapeutic potentials of Kunxian capsule to alleviate DN by regulating the imbalance of immune-inflammation system.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.

Objective:To observe the effect of microelectronic EMG bridge (EMGB) training on the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury. Methods:From March, 2016 to March, 2017, 20 patients with complete cervical 5 spinal cord injury were randomly divided into control group (n = 10) and experimental group (n = 10). The control group received routine wrist extensor muscle training, and the experimental group received EMGB training in addition, for 180 days. The motor function of the affected limb was evaluated by sEMG of extensor carpi radialis longus, Manual Muscle Test (MMT), Wolf Motor Function Test (WMFT) and Spinal Cord Lesion Independence Measure (SCIM). Results:After treatment, the peak value and average value of sEMG of extensor carpi longus of both sides increased in both groups (t > 2.510, P < 0.05), the peak value and average value of the left side were higher (t > 2.759, P < 0.05), and the peak value of the right side was higher (t = 2.691, P < 0.05) in the experiment group than in the control group, however, there was no significant difference in average value of the right side between two groups (t = 2.063, P = 0.054). The scores of MMT increased in both groups (t > 2.569, P < 0.05), and were higher in the experimental group than in the control group (t > 2.278, P < 0.05). The scores of WMFT and SCIM increased in both groups (t > 3.839, P < 0.05), however, there was no significant difference between two groups (t < 1.498, P > 0.05). Conclusion:EMGB training could improve the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury.