Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective ef-fects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRα signaling.It is reported that LXRα regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanol-amine(PE)by promoting ATCL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATCL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

Objective:To summarize experience and effect of the stylized operation step in the neck endoscopic thyroidectomy for papillary thyroid microcarcinoma (PTMC).Methods:The clinical data of 51 patients who underwent transthoracic breast approach scarless neck endoscopic thyroidectomy (SET) from January 2018 to September 2019 in Tungwah Hospital Affiliated to Sun Yat-sen University were retrospectively analyzed. The operative procedure used stylized operation steps: establishment of operating space, three-step method thyroidectomy, central lymph node dissection (CLND), close operating space.Results:Among 51 patients, 25 cases underwent unilateral thyroidectomy plus isthmic resection, 26 cases underwent total/near-total thyroidectomy, and 16 cases underwent preventive CLND. The recurrent laryngeal nerve (RLN) was exposed in all 51 cases, the external branches of the superior laryngeal nerve (EBSLN) was exposed in 35 cases, no procedure was converted into open neck incision thyroidectomy. Forty-two cases were followed up, 2 cases had postoperative hoarseness and unilateral recurrent laryngeal nerve paralysis, which were recovered 55 and 75 d after operation respectively. There was no bucking, voice blunt or permanent low calcium. One patient had abnormal sensation of neck skin after operation, and recovered gradually 3 months after operation.Conclusions:The stylized operation step in the SET can increase safety of surgery.

Objective:To analyse the long-term efficacy in childhood T-cell acute lymphoblastic leukemia (T-ALL) cases enrolled in the national protocol of childhood leukemia in China-acute lymphoblastic leukemia (NPCLC-ALL) 2008.Methods:Clinical data of 96 patients diagnosed as T-ALL and treated with NPCLC-ALL2008 protocol between January 2009 and December 2017 in the Department of Hematology-Oncology, the Children′s Hospital, Zhejiang University School of Medicine were analyzed retrospectively. Predictive value of minimal residual disease (MRD) monitored by flow cytometry was analyzed. Kaplan-Meier method was used for long-term survival analysis.Results:A total of 96 evaluable patients with newly diagnosed T-ALL were analysed, including 72 males and 24 females. The age was 9.5 (ranged from 1.0 to 16.0) years. The follow-up time was 5.7 (ranged from 1.0 to 9.7) years. Among 96 patients, 92 (96%) achieved complete remission. The 5-year event free survival (EFS) and overall survival (OS) rates were (61±6) % and (70±5) %, respectively. Relapse occurred in 18 cases and the 5-year cumulative incidence of relapse was (27±6) %. Twenty-four patients died. The 5-year OS rates of patients with MRD>5% on day 15 of induction therapy was significantly worse than those with MRD≤5% ((60±12) % vs. (72±6) %, χ 2=3.904, P=0.048) . The 5-year EFS and OS rates were obviously lower in patients with MRD>10% before the consolidation therapy ((50±35) %). The 5-year OS rates of patients with relapsed disease was significantly worse than those without ((26±13) % vs. (81±5) %, χ 2=18.411, P<0.01). The earlier the relapse, the worse the prognosis. The 5-year OS rates for patients relapsed within 6 months, within 3 years and more than 3 years, were (25±22) %, (30±14) % and (50±35) % respectively (χ 2=13.207, P<0.01). Conclusions:NPCLC-ALL2008 protocol is effective for childhood T-ALL. The MRD guided accurate risk stratification and individualized treatment can reduce the relapse and improve the survival rate of pediatric T-ALL.

Objective To retrospectively review the clinical characteristics and antimicrobial resistance profile of nosocomial bloodstream infections caused by Klebsiella pneumoniae in surgical patients for better use of antimicrobial agents.Methods The clinical data of the surgical patients who were diagnosed with K.pneumoniae-associated bloodstream infections in Tung Wah Hospital from January 2013 to June 2015 were reviewed and analyzed retrospectively.The diagnosis of bloodstream infections was based on national diagnostic criteria.The pathogens were routinely isolated and identified.Antimicrobial susceptibility testing was carried out by using Kirby-Bauer method.The data were analyzed by WHONET 5.6 software.Results A total of 78 surgical patients were identified with nosocomial bloodstream infections due to K.pneumoniae during this period,including primary bloodstream infections (12.8％,10/78) and secondary bloodstream infections (87.2％,68/78).These infections were mainly associated with surgical and invasive procedures.Nearly 40％ of the K.pneumoniae isolates were resistant to ceftriaxone,cefuroxime and piperacillin.ESBLs were produced in 43.6％ (34/78) of the K.pneumoniae isolates.The ESBLs-producing strains showed significantly higher resistance rates to various antibiotics than non-ESBLs-producing strains.Piperacillin-tazobactam,amikacin,imipenem,and meropenem still have good antibacterial activity against these K.pneumoniae isolates.However,imipenem-resistant strains are emerging.Conclusions Most of the bloodstream infections caused by K.pneumoniae were secondary to infections in other body sites in surgical patients.Hospital infection control measures should be strengthened.Meanwhile,the clinicians should take full advantages of microbiological laboratory to profile the pathogens and their susceptibility patterns,which is crucial for rational use of antibiotics.

Objective To observe the PML protein expression of hepatocellar carcinoma tissue and cells lines and As 2 O3 regulate its expression .Methods Immunohistochemistry was used to examine the PML protein expression of hepatocellar carcinoma tissue . Western blot analysis were used to observe PML protein expression of hepatocellar carcinoma tissue of 12 cases ,5 hepatocellar car-cinoma cell lines ,such as HuH7 ,HepG2 ,Hep3B ,SMMC-7721 ,MHC97H .Western blot analysis was used to detected the PML pro-tein expression of these hepatocellar carcinoma cell lines after 72-96 h treated with 0 .25 μg/mL of As2 O3 .Results Immunohisch-enmical staining showed that the PML protein was expressed in both cytoplasm and nucleus ,did not well-distributed in hepatocellar carcinoma cells .There was no significant differences of PML protein expressed among differently differentiated stages of hepatocel-lar carcinoma cells .Western blot analysis found that hepatocellar carcinoma tissues of 12 cases with hepatocellar carcinoma ex-pressed PML protein ,and there was significant difference of PML protein expressed among 12 cases suffer with hepatocellar carci-noma .hepatocellar carcinoma cell lines ,such as HuH7 ,HepG2 ,Hep3B ,SMMC-7721 and MHC97H all expressed PML protein ,and there was little difference of PML protein expressed among hepatocellar carcinoma cell lines .The PML protein expression of HuH7 ,HepG2 ,Hep3B ,SMMC-7721 and MHC97H cell after 72-96 h treated with 0 .25 μg/mL of As2O3 significant decreased . Conclusion Hepatocellar carcinoma tissue and cells may express PML protein ,and As2 O3 may regulate this protein expression as well .PML protein may be the target molecule of As2 O3 treating HCC .

Objective To evaluate the treatment effects of the olecranon comminuted fracture by the angle stability prin-ciple combined with support under the articular surface. Methods From November 2008 to June 2012, 13 patients (7 male and 6 female, aged from 20 to 77 years) suffered from olecranon comminuted fracture were treated with Synthes anatomy locking com-pression plate and screws combined with Kirschner wires supporting under the articular surface through the posterior median ap-proach. Fractures occurred in the left elbow in 9 and in the right elbow in 4. According to the Mayo classification, 11 cases were classified as Mayo type IIB and 2 as IIIB. According to the Schatzker-Schmeling classification, 2 fractures were type A2, 9 type C, and 2 type D. One patient with type C fracture also had type I coronoid fracture according to Regan and Morrey classification. The Mayo elbow performance index (MEPI) and the shortened disabilities of the arm shoulder and hand (Quick-DASH) were employed to evaluate the functions. All patients took the satisfaction survey and X-ray during the follow-up. Results All patients were fol-lowed-up for 8 to 41 months. The mean ROM of the elbow joint was 112° (range, 65°-140° ), and the mean rotation angle of the forearm was 170° (range, 150°-180°). The mean score for the MEPI was 96 (range, 85-100), excellent 12, good 1. The mean score for the Quick-DASH was 6.2 (range, 0-16.7). In the satisfaction survey, 8 patients were very satisfied, 4 satisfied, 1 common level. All patients took the X-ray during the follow-up and all of them had achieved fracture union completely with the mean time period as 12.7 weeks (range, 11-24 weeks). No cubitus varus, valgus, and instability were found in all patients. No complication, such as infection, ulnar nerve injuries and etc. was found. Five patients complained about mild discomfort caused by internal fixation at 3 months after surgery. Three of them were diagnosed as joint stiffness because of ROM within 100° . One case in 3 elbow stiffness patients developed osteoarthritis after eight months, but no pain during joint activity. Internal fixation was removed in one case;an-other young patient took the operation for removal of internal fixation and release of medial ligament;the third patient refused oper-ation. Conclusion Angle stability principle (Synthes anatomy locking compression plate and screws) combined with supporting under the articular surface (Kirschner wires) can achieve stable fixation in treating olecranon comminuted fracture. It may realize the early exercise of the elbow joint with excellent clinical results. Therefore, it may be an optional choice in clinical practice.

BACKGROUND:The most effective method for the treatment of acetabular fracture is open reduction and internal fixation, however, this treatment for some special types of acetabular fracture cannot get satisfactory prognosis, and is prone to complications, such as traumatic coxarthrosis and avascular necrosis of femoral head. OBJECTIVE:To evaluate the curative effect of open reduction and internal fixation and total hip arthroplasty in the treatment of special acetabular fracture. METHODS:Twelve cases of acetabular fracture were included, including seven cases of traffic accident wound, three cases of crush injury, and two cases of fal ing injury. The type of bone fracture:two cases of posterior wal fracture, two cases of posterior column and posterior wal fracture, one case of T shaped fracture, five cases of transverse and posterior wal fracture, and two cases of acetabular roof sexual fracture. Complications:one case was femoral head centric dislocation, five cases were latter dislocation, and three cases were caput femoris fractures. Before injury, three cases had coxarthrosis, and two cases were avascular necrosis of femoral head. Al the cases were treated with open reduction internal fixation and total hip arthroplasty, of which nine cases were treated with biological prosthesis, and three cases were treated with bone cement prosthesis. The time from hospitalization to surgery was 3-15 days, and average was 6 days. The patients were fol owed-up once every 2 months in 1 year after replacement, and the Harris score was used to evaluate the hip function recovery. RESULTS AND CONCLUSION:No surgical site and deep wound infection, joint dislocation, lower limb deep vein thrombosis, and death were found in these 12 cases. Among them, 11 cases were fol owed-up for a longtime;the fol ow-up was lasted for 6-82 months. The acetabular fracture was healed at 6-16 months after reduction without prosthesis loosening and sinking. The hip function was evaluated during final fol ow-up according to the Harris score:excellent in eight cases, good in two cases, poor in one case, and the excellent and good rate was 91%. Open reduction internal fixation and one-stage total hip arthroplasty can avoid long-term bed, get out of bed as soon as possible, and reduce complications, thus reconstruct the hip joint painlessly and good functional y.

ObjectiveTo discuss the more aesthetic and minimally invasive surgical approach of endoscopic thyroidectomy.Methods50 cases of endoscopic thyroidectomy via breast areola-axillary approach were retrospectively analyzed.Among these cases,12 received unilateral partial lobectomy,30 received unilateral total lobectomy and 8 received bilateral partial lobectomy.Results Endoscopic thyroidectomy was completed in all the patients.The intraoperative blood loss was ( 12.77 ± 20.12 ) ml.The operation time was (67.00 ± 21.28 )min.The postoperative hospital stay was (3.77 ± 0.50)days.Hoarseness occurred in 2 cases.All the 50 cases were followed up from 1 to 6 months and no other complication occurred.ConclusionEndoscopic thyroidectomy via breast areola-axillary approach is more aesthetic and minimally invasive; however,the operator needs an adaptive process for a better surgical view angle.

ObjectiveTo evaluate the application value of the emergency laparoscopic surgery in incarcerated inguinal hernia of children. MethodsManual reduction of incarcerated hernia was laparoscopic- assisted after anesthesia, high-ligation of hernia sac was done by one hole method of laparoscopic treatment.ResultsAll of 22 cases of pediatric incarcerated hernia were done, no complications occurred. Eighteen patients were followed up for 3 - 15 months, 9.3 months on average, without serious complications. ConclusionsThe emergency laparoscopic surgery in children of incarcerated inguinal hernia is safe and feasible,with smaller trauma, quicker recovery and smaller health risk.