[Evaluation of arthroscopic anterior talofibular ligament and calcaneofibular ligament repair separately for chronic lateral ankle instability in conjunction with subtalar instability].

Objective: To investigate the clinical efficacy of simultaneous arthroscopic repair of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for treating chronic lateral ankle instability (CLAI) in conjunction with subtalar instability (STI). Methods: This is a retrospective case series study. The clinical data of 15 patients with ankle arthroscopic in the Department of Hand and Foot Surgery, the Second Affiliated Hospital of Soochow University from January 2019 to December 2022 were analyzed retrospectively. There were 11 male cases and 4 female cases, aged (28.6±1.5) years (range: 19 to 39 years). All the patients were evaluated by manual inversion stress X-ray and MRI before operation. Arthroscopically observing and then repairing the ATFL and CFL separately after further diagnostic confirmation. One year after operation, MRI was performed, and pain visual analogue score(VAS), American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle functional scale(KAFS) were evaluated. Data were compared using paired sample t test. Results: The follow-up period was (23.6±2.3) months (range: 12 to 30 months). At last follow-up,the VAS decreased from 6.1±1.4 preoperatively to 1.4±1.2(t=9.482, P<0.01).The AOFAS-AH improved from 50.5±11.7 preoperatively to 94.2±6.1(t=-13.132, P<0.01), and the KAFS improved from preoperatively 44.3±10.8 to 90.8±6.4 (t=-12.510, P<0.01). There was no complication such as recurred instability or joint stiffness. Conclusions: Arthroscopically repairing the ATFL and CFL separately can effectively restore the stability of the ankle and subtalar joint with small trauma. Patients can recover quickly after surgery. It provides a new idea for the clinical treatment of CLAI combined with STI.

[Clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation].

Objective: To explore the clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation. Methods: A retrospective observational study was conducted. From January to August 2021, 5 patients with secondary rejection wounds after brain pacemaker implantation who met the inclusion criteria were admitted to the Wound Repair Center of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, including 3 males and 2 females, aged 56-69 years, with the wound developed at the pulse generator implantation site in the chest in 2 cases, at the connection site of the wire and electrode behind the ear in 2 cases, and at both the chest and the back of the ear in 1 case. All the wounds were repaired by pedicled omental flap transplantation. The wound area after debridement was 2-15 cm2. After operation, the wound healing and related complications (pain, infection, incisional hernia, omental flap necrosis, etc.) were observed. During follow-up, the recurrence of the wound was observed. Results: The wounds of all 5 patients healed within 2 weeks after operation, without related complications. During follow up of 12-18 months, 1 patient got a recurrence of rejection wound behind the left ear 4 months after surgery and eventually had the brain pacemaker removed; the other 4 patients had no recurrence of wounds. Conclusions: Pedicled omental flap transplantation can repair the secondary rejection wounds after brain pacemaker implantation safely and effectively, with few postoperative complications.

[Clinical manifestations of Langerhans cell histiocytosis with multisystem involvement in 53 children].

Objective: To analyze the clinical characteristics and long-term outcome of Langerhans cell histiocytosis with multisystem involvement (MS-LCH) in children, and to evaluate the efficacy of modified DAL-HX83/90 protocol. Methods: This retrospective study included 53 patients with MS-LCH admitted to the Department of Pediatric Hematology and Oncology, First Affiliated Hospital of Zhengzhou University from January 2011 to May 2019. Modified DAL-HX83/90 protocol was used in all patients as an initial treatment. The patients were divided into the group with (RO+) or without (RO-) risk organ involvement. The RO+group was further divided into two groups, as RO+Ⅰ group (lung involvement only) and RO+Ⅱ group (extra-pulmonary, with or without lung involvement). The clinical characteristics and the long-term outcome were summarized. Event-free survival (EFS) and overall survival (OS) curves were analyzed with Kaplan-Meier method. Univariate and multivariate analysis of prognostic factors including age, sex, risk organ involvement and response to 6-week induction were analyzed with Log-Rank test and Cox proportional hazards models. Results: Among the 53 children with MS-LCH, 34 were male and 19 were female. The age of onset was 21 months (3 months-13 years). There 22 were in RO+group, with 12 in RO+Ⅰ group and 10 in RO+Ⅱ group, and 31 in RO-group. The follow-up period was 51 (12-144) months. The overall response rate of 6-week induction was 89% (47/53), and the recurrence rate was 30% (16/53). The 5-year EFS and OS were (67±6) % and (83±5) %, respectively. Univariate analysis showed that the 5-year EFS and OS of patients who responded well to 6-week induction chemotherapy were significantly higher than those who had no response ((76±6) % vs. 0, (88±4) % vs. (41±22) %, χ2 = 34.743, 10.608, both P<0.05). The 5-year EFS and OS of RO-group were significantly higher than that of RO+group ((80±7) % vs. (49±10) %, (93±4) % vs. (70±10) %, χ2=6.022, 4.793, both P<0.05). And the 5-year EFS of RO+Ⅰ group was significantly higher than that of RO+Ⅱ group ((83±10) % vs. (10±9) %, χ2=9.501, P=0.002). While age and sex were not significantly associated with 5-year EFS and OS (all P>0.05). Cox proportional hazard regression model showed that response to 6-week induction chemotherapy was the independent risk factor for EFS (HR=13.114, 95%CI 3.759-45.742, P<0.01) and OS (HR=7.748, 95%CI 1.542-38.920, P=0.013). Conclusions: Most of the children without risk organ involvement treated with modified DAL-HX83/90 protocol could achieve long-term survival. However, the children involved liver, spleen, or hematopoietic system had a high risk of disease progression and recurrence.

[Clinical analysis of 26 children with postoperative residual or recurrent fibrosarcoma].

Objective: To evaluate the long-term outcomes and prognostic factors of postoperative residual or recurrent fibrosarcoma in children. Methods: Clinical data of 26 patients continually admitted to Shanghai Children's Medical Center between April 2004 and February 2019 with postoperative residual or recurrent fibrosarcoma were analyzed retrospectively. All patients were treated with Shanghai Children's Medical Center-rhabdomyosarcoma-1999 (SCMC-RS-99) regimen and timely radical tumor resection. Before chemotherapy, according to the surgery and imaging examination, 26 patients were divided into 2 groups: postoperative residual group and postoperative recurrent group. Clinical features and long-term follow-up results of patients were summarized. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event-free survival (EFS) rates, Log-Rank test and Cox proportional hazards models were used for univariate and multivariate prognostic analysis of factors including age (<3 years or 3-18 years old), gender, primary tumor site, postoperative stage, disease status, ETS variant 6 (ETV6) gene and chemotherapy drugs. Results: Among 26 cases, 13 were male and 13 were female, 17 cases were in postoperative residual group and 9 cases were in postoperative recurrent group. Until the last follow-up at December 31, 2019, the median follow-up time was 73 months (ranged from 10 to 188 months).The 5-year OS and EFS rates were (86±7)% and (77±9)%. Univariate analysis showed that, the 5-year EFS rate of postoperative residual group was significantly higher than that of the postoperative recurrent group ((94±5)% vs.(63±16)%,χ(2)=5.106,P=0.024), the 5-year EFS rate of patients <3 years old was significantly higher than that of patients 3-18 years old ((94±5)% vs. (62±17)%, χ(2)=6.507, P=0.011). Gender (χ(2)=0.445), primary tumor site (χ(2)=0.258), postoperative stage (χ(2)=3.046), ETV6 gene (χ(2)=1.496), and whether doxorubicin-containing drugs in chemotherapy (χ(2)=1.692) did not exhibit significant impact on 5-EFS rate (all P>0.05). Age, postoperative stage and disease status were included in COX proportional risk model for multivariate analysis, which showed that age >3 years old (HR=8.95, 95%CI 0.73-109.50, P=0.086), stage Ⅲ-Ⅳ (HR=16.50, 95%CI 0.84-321.40, P=0.065) and postoperative recurrence (HR=10.60, 95%CI 0.84-134.30, P=0.068) had no significant impact on EFS rate. Conclusion: Children with postoperative residual or postoperative recurrent fibrosarcoma still had good remission rate and long-term survival, especially young children without recurrence have a significant survival advantage.

LncRNA DANCR regulates osteosarcoma migration and invasion by targeting miR-149/MSI2 axis.

OBJECTIVE: As a new LncRNA, anti-differentiated non-coding RNA (DANCR) plays an important role in tumorigenesis and development, and its molecular mechanism in osteosarcoma is unclear. In this study, by investigating osteosarcoma tissue and cells, we explored the molecular mechanism by which lncRNA DANCR regulates the occurrence and development of osteosarcoma by targeting the miR-149 / MSI2 axis. PATIENTS AND METHODS: In this study, osteosarcoma tissues and adjacent tissues in 109 patients were collected, and the relative expression of DANCR was detected by qPCR. The correlation between DANCR expression and clinical classification was statistically analyzed. In order to explore the potential molecular mechanism of DANCR related to tumor migration and invasion, an overexpression and silencing test was performed on the osteosarcoma cell line Saos-2, and then qPCR method was used to test the expression of miR149, and cell scratch test was used to detect invasion after DANCR silencing and miR149 overexpression. Transwell assay was used to detect the invasion after DANCR silencing and miR149 overexpression. Finally, Western blot was used to verify the expression of MSI2 protein after overexpression and silencing of miR-149. RESULTS: DANCR was significantly up-regulated in both osteosarcoma tissue and cells. The high expression of DANCR was significantly positively correlated with tissue typing and advanced TNM stage. DANCR can significantly reduce the migration and invasion of osteosarcoma cells. miRNA overexpression significantly reduced osteosarcoma cell migration and invasion. When miR-149 was overexpressed, MSI2 protein expression was significantly down-regulated. When miR-149 was silenced, MSI2 protein was significantly up-regulated. CONCLUSIONS: LncRNA DANCR plays an important regulatory role in the occurrence and development of osteosarcoma. It may be used as a potential target in the treatment of osteosarcoma in the future, by targeting the miR-149/MSI2 axis to regulate the occurrence and development of osteosarcoma.

Mechano growth factor interacts with nucleolin to protect against cisplatin-induced neurotoxicity.

Mechano growth factor (MGF) is an alternatively spliced form of insulin-like growth factor-1 (IGF-1) that has shown to be neuroprotective against 6-hydroxydopamine toxicity and ischemic injury in the brain. MGF also induces neural stem cell proliferation in the hippocampus and preserves olfactory function in aging mice. Cisplatin is a chemotherapy drug that induces peripheral neuropathy in 30-40% of treated patients. Our studies were designed to see if MGF would protect dorsal root ganglion (DRG) neurons from cisplatin-induced neurotoxicity and to identify potential mechanisms that may be involved. Expression of endogenous MGF in adult DRG neurons in vivo ameliorated cisplatin-induced thermal hyperalgesia. Exogenous MGF and MGF with a cysteine added to the N-terminus (CMGF) also protected embryonic DRG neurons from cisplatin-induced cell death in vitro. Mass spectroscopy analysis of proteins bound to MGF showed that nucleolin is a key-binding partner. Antibodies against nucleolin prevented the neuroprotective effect of MGF and CMGF in culture. Both nucleolin and MGF are located in the nucleolus of DRG neurons. RNAseq of RNA associated with MGF indicated that MGF may be involved in RNA processing, protein targeting and transcription/translation. Nucleolin is an RNA binding protein that is readily shuttled between the nucleus, cytoplasm and plasma membrane. Nucleolin and MGF may work together to prevent cisplatin-induced neurotoxicity. Exploring the known mechanisms of nucleolin may help us better understand the mechanisms of cisplatin toxicity and how MGF protects DRG neurons.

A QM protein from Bombyx mori negatively regulates prophenoloxidase activation and melanization by interacting with Jun protein.

The QM gene that encodes for the ribosomal protein L10 was firstly identified from human tumour cells as a tumour suppressor. In this study, a QM gene was identified in silkworm Bombyx mori (BmQM) and its immunomodulatory function was explored. BmQM messenger RNA (mRNA) and protein were highly expressed in the silk gland and fat body, and expressed in all stages of silkworm growth. After challenged with four different microorganisms, the expression levels of BmQM mRNA in fat body or haemocytes were significantly upregulated compared with the control. After knock-down of BmQM gene, the expressions of some immune genes (PGRPS6, Gloverin0, Lysozyme and Moricin) were affected, and the transcripts of prophenoloxidase1 and prophenoloxidase2 have different degrees of change. The phenoloxidase activity was significantly reduced when the purified recombinant BmQM protein was injected. Recombinant BmQM protein inhibited systemic melanization and suppressed prophenoloxidase activation stimulated by Micrococcus luteus, but it did not affect phenoloxidase activity. Far-western blotting assays showed that the BmQM protein interacted with silkworm BmJun protein, which negatively regulates AP-1 expression. Our results indicated that BmQM protein could affect some immune gene expression and negatively regulate the prophenoloxidase-activating system, and it may play an important role in regulation of the innate immunity in insects.

[Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China].

The correct thoughts and principles of diagnosis and treatment of chronic refractory wounds need to be formulated. Through the relevant domestic and international consensus and based on clinical experience, the Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China is proposed. It is considered that in the diagnosis and treatment of chronic refractory wounds, in the case of fully understanding the patient's medical history, the following thoughts and principles should be complied in order. (1) Pay attention to the cleanliness of the wound after being cleaned. (2) Reasonably perform debridement to avoid being " excessive" or " not thorough". (3) Reasonably perform examination, diagnosis, and differential diagnosis of pathogenic factors. (4) Treat according to etiology. (5) Find comorbidities and prevent adverse outcomes. (6) Select the correct wound treatment method reasonably and timely. When the conservative wound care treatment is considered, pay attention to embodying the concept of etiological treatment, treat the wound according to the principles of safety, phase, selectivity, and effectiveness, and make a reasonable choice of continuing conservative treatment or surgical treatment in time after completing the preparation of the wound bed. When surgical treatment is considered, pay attention to the selection of reasonable surgical method and donor site, pay attention to the healing rate of surgical wound site and the outcome of donor site, and give reasonable protection to the wound site after surgery. (7) Carry out rehabilitation treatment after wound healing and related health education.

Diagnostic and prognostic implications of serum miR-101 in osteosarcoma.

Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma.

Transduced Heme Oxygenase-1 Fusion Protein Reduces Renal Ischemia/Reperfusion Injury Through Its Antioxidant and Antiapoptotic Roles in Rats.

INTRODUCTION: Heme oxygenase-1 (HO-1) has a protective role against ischemia/reperfusion (I/R) injury. METHODS: We produced an HO-1 fusion protein mediated by cell penetrated peptide PEP-1, also known as PEP-1-HO-1 fusion protein, and investigated its role in renal I/R injury in rats. Male Sprague-Dawley rats were subjected to 45 minutes of ischemia by occluding the bilateral renal arteries and 6 hours of reperfusion to prepare the model of renal I/R. Animals were randomized to receive PEP-1-HO-1 fusion protein or equal volume of physiologic saline 30 minutes before ischemia. RESULTS: Administration of PEP-1-HO-1 fusion protein resulted in a significant increase in HO-1 expression. His-probe expression (1 part of the PEP-1-HO-1 fusion protein) was only observed in PEP-1-HO-1-treated animals. I/R caused renal dysfunction and increases in malondialdehyde level and cell apoptosis, and decreased superoxide dismutase activity. Treatment of PEP-1-HO-1 fusion protein reversed these changes. Furthermore, administration of PEP-1-HO-1 inhibited the I/R-induced increase in nuclear factor-κB activation. CONCLUSIONS: These findings suggest that transduction of PEP-1-HO-1 attenuates renal I/R injury in rats, which might be partly attributable to its antioxidant and antiapoptotic effects.

Requirement for pre-existing of p21 to prevent doxorubicin-induced apoptosis through inhibition of caspase-3 activation.

Doxorubicin (DOX)-induced apoptosis is suppressed by p21 (waf1/cip1/sdi1), a cyclin dependent kinase (CDK) inhibitor. Here we show that exogenous expression of p21 before, but not after, the DOX-treatment protected p21-deficient human colorectal cancer cell line DLD1 from DOX-induced apoptosis. In previous work, we demonstrated that p21 inhibits DOX-induced apoptosis via its CDK-binding and CDK-inhibitory activity. Here we report that pre-existing p21 can associate with pro-caspase-3 and inhibit caspase-3 activation in the cells, which was at least in part responsible for enhancing survival of DOX-treated cells. Furthermore, the N-terminal domain of p21 was found to interact with pro-caspase-3 in DLD1 cells. Thus, we propose that pre-existing p21 is required to prevent DOX-induced apoptosis.

Intraarticular triamcinolone acetonide for pain control after arthroscopic knee surgery.

UNLABELLED: Intraarticular corticosteroids provide valuable local therapy for chronic joint pain caused by inflammatory joint diseases. In this inpatient study, we evaluated the effect of intraarticular triamcinolone acetonide on acute pain after arthroscopic knee surgery. Sixty patients who underwent arthroscopic knee surgery under spinal anesthesia were enrolled into this double-blind, randomized trial. At the end of surgery, Group 1 (n = 30) received intraarticular triamcinolone acetonide 10 mg in isotonic saline 20 mL, and Group 2 (n = 30) received intraarticular isotonic saline 20 mL. After surgery, pain was assessed by using a visual analog scale. The time to first analgesic request (IV morphine) was recorded, and the proportion of patients requiring rescue analgesia was calculated. The results demonstrated that patients in Group 1 had lower pain scores than those in Group 2 from 6 to 24 h postoperatively (P < 0.05 to P < 0.01). From 6 h to 24 h, no patient in Group 1, compared with 53% of patients in Group 2, requested rescue analgesia (P < 0.001). We conclude that intraarticular triamcinolone acetonide provides a valuable local therapy of acute joint pain after arthroscopic knee surgery. IMPLICATIONS: The value of intraarticular triamcinolone acetonide in the management of pain after arthroscopic knee surgery has been evaluated. Patients who received intraarticular triamcinolone acetonide 10 mg at the end of surgery had lower pain scores and used less systemic analgesia than the saline control group. These data are important to the clinical use of this new therapy.

In vivo regulation of apolipoprotein A-I gene expression by estradiol and testosterone occurs at the translational level in inbred strains of mice.

Testosterone and estrogen alter the hepatic synthesis of apoA-I in castrated inbred strains of mice, but apoA-I mRNA levels remain unaltered, suggesting post-transcriptional regulation of apoA-I production in liver. To test this hypothesis, females of the C3H/HeJ and C57BL/6J strains of mice were castrated and after 2 weeks were given testosterone propionate (Testo 1 microgram/g body weight/day,), 17 beta-estradiol (0.16 or 5 microgram/g/day, E2L, E2H, respectively) or vehicle (placebo) for 14 days (n = 5/group). Liver polysomes were isolated from pooled livers of each group and "run-off" assays were performed. Testo increased apoA-I gene translation to 124% and 171% of controls in C3H and C57BL strains, increased polysomal mRNA levels to 276% and 438% and increased apoA-I synthesis to 181% and 269% of respective controls. Decreases in polysomal "run-off", mRNA levels and apoA-I synthesis were produced by E2H. E2L produced non-parallel changes, i.e., it raised apoA-I synthesis and polysomal apoA-I mRNA, but did not affect rates of translation. The data suggest that sex hormones exert their effects on apoA-I gene expression at the translational level.

In vivo regulation of apolipoprotein A-I gene expression by estradiol and testosterone occurs by different mechanisms in inbred strains of mice.

We tested the hypothesis that testosterone and estrogen modulate apoA-I gene expression and metabolism by different mechanisms that may be influenced by genetic factors. Male and female C3H/HeJ (atherosclerosis-resistant) and C57BL/6J (atherosclerosis-susceptible) mice (n = 5/group) were castrated (Placebo). Castrates were given 17 beta-estradiol (E2) at 0.16 microgram/g (E2L) or 5 micrograms/g (E2H) body weight per day, or testosterone (Testo) 1 microgram/g per day, 14 days after surgery, for 14 days. Plasma total cholesterol concentrations (TC) were higher in male Placebo mice than in females. Testosterone altered TC and high density lipoprotein (HDL) cholesterol by gender and strain; however (HDL-C)/TC ratios and apoA-I concentrations were unaltered. Testosterone did reduce HDL particle diameters in both genders of C3H mice only. Low density lipoprotein-cholesterol (LDL-C)/TC ratios remained constant and apoB increased in males only. E2L and E2H decreased TC, HDL-C/TC ratios, and apoA-I. Decrements varied by strain. HDL diameters decreased in both genders in C3H mice only; however, HDL size distributions were altered in both strains. LDL-C/TC ratios increased in all groups. E2L mice showed variable responses of apoB, but apoB rose uniformly in all E2H groups. Testosterone increased and E2H decreased hepatic apoA-I synthesis. ApoA-I mRNA concentrations remained stable in both Testo and E2 groups. ApoA-I gene transcription varied by strain and gender, but all changes were less than twofold. Testosterone did not affect hepatic apoB or LDL receptor mRNA, however, E2H increased both mRNAs in males but not in females. On Western blotting of liver membranes, E2H had little effect on mouse LDL receptor protein mass; by contrast, E2H increased LDL receptor approximately threefold in rats. In summary, responsiveness of mouse lipids to testosterone and E2 vary by strain and gender. Testosterone and E2 differ in their regulation of apoA-I production mainly at the level of translation. Hormones operate at several levels of gene regulation, suggesting that complex mechanisms are involved. Mice differ from rats and rabbits in their LDL receptor responsiveness to estradiol treatment.