ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

Diabetic retinopathy (DR), a neurovascular complication of diabetes, presents a multifaceted pathogenesis that encompasses numerous biological processes and molecular mechanisms. Endoplasmic reticulum stress (ERS) plays a critical role in the maintenance of cellular homeostasis, and diabetic neuromicroangiopathy is driven by high glucose, which activated ERS through the promotion of protein misfolding, oxidative stress, and disturbances in calcium homeostasis. ERS activates the unfolded protein response, thereby influencing the onset and progression of DR through modulating mitochondria-associated endoplasmic reticulum membranes, autophagy, apoptosis, microvascular function, oxidative stress, and inflammation pathways. Currently, the principal interventions against ERS comprise the modulation of the ERS signalling axis and its interactions with associated pathological processes such as autophagy, oxidative stress, and inflammation, through pharmacological and molecular mechanisms. These interventions are directly or indirectly shown to inhibit persistent ERS and are demonstrated to ameliorate DR. With the in-depth study of ERS and the research and development of various drugs for ERS, it is expected to bring novel insights and strategies for DR management in the future.

AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in-hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im-proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu-mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi-bition of ferroptosis.

Diabetic retinopathy (DR), a neurovascular complication of diabetes, presents a multifaceted pathogenesis that encompasses numerous biological processes and molecular mechanisms. Endoplasmic reticulum stress (ERS) plays a critical role in the maintenance of cellular homeostasis, and diabetic neuromicroangiopathy is driven by high glucose, which activated ERS through the promotion of protein misfolding, oxidative stress, and disturbances in calcium homeostasis. ERS activates the unfolded protein response, thereby influencing the onset and progression of DR through modulating mitochondria-associated endoplasmic reticulum membranes, autophagy, apoptosis, microvascular function, oxidative stress, and inflammation pathways. Currently, the principal interventions against ERS comprise the modulation of the ERS signalling axis and its interactions with associated pathological processes such as autophagy, oxidative stress, and inflammation, through pharmacological and molecular mechanisms. These interventions are directly or indirectly shown to inhibit persistent ERS and are demonstrated to ameliorate DR. With the in-depth study of ERS and the research and development of various drugs for ERS, it is expected to bring novel insights and strategies for DR management in the future.

AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in-hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im-proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu-mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi-bition of ferroptosis.

Objective:To describe the treatment of the first carpometacarpal arthritis in Eaton Ⅱ, Ⅲ combining the hemi excision of trapezium with tendon ball and evaluate its clinical efficacy.Methods:Data of patients with the first carpometacarpal arthritis who were treated by hemi excision of trapezium and tamponade of the tendon ball from March 2013 to October 2018 were retrospectively analyzed. Twelve patients were all females with an average age of 55±2.8 years (range, 48-61 years). There were 3 cases of left thumbs and 9 cases of right. The study was only researched with primary osteoarthritis patients, preoperative imaging Eaton stages, including 8 cases inⅡstage, 4 cases in Ⅲ stage. Postoperative X-ray examination was performed, and the subsidence rate of the first metacarpal bone was evaluated according to height of arthroplasty. Preoperative and postoperative pain was evaluated according to visual analogue scales (VAS) score and DASH score. Preoperative and postoperative finger movement was evaluated according to the changes in preoperative and postoperative grip and pinch force.Results:The average follow-up period was 12±4.8 months (range, 6-17 months). The mean score of VAS after operation was 1.2±1.0 which was lower than 6.3±1.5 before operation ( t=13.4, P=0.0001); DASH score after operation was 26.2±9.6 which was lower than 48.9±13.0 before operation ( t=5.7, P=0.0001); Grip force after operation was 25.5±6.8 kg which was higher than 15.0±2.9 kg before operation ( t=7.3, P=0.0001); Pinch force after operation was 3.2±0.8 kg which was higher than 2.1±0.4 kg before operation ( t=3.6, P=0.0045), and all of these four above data has statistic difference. At the latest postoperative follow-up, the height index of arthroplasty was 0.299±0.022, and there was no significant change ( F=1.337, P=0.276) when compared with 0.306±0.021 before surgery and 0.313±0.024 after surgery. After the operation, 2 patients presented with incision redness and swelling and exudation. It was considered that local hematoma in the intra-articular operation could not be completely absorbed. After several dressing changes, the redness and swelling subsided and the exudation was controlled. Conclusion:Preserving the proximal joint surface of trapezium and tamponading tendon ball, could reduce the subsidence rate of the first metacarpal bone and alleviate the pain of the first carpometacarpal joint, thus may effectively improve the joint function. It has a significant effect on the treatment of Eaton Ⅱ,Ⅲ stage of the first carpometacarpal arthritis.

Objective: To investigate the feasibility and clinic outcome of the turbocharging technique in repairing large defect with free perforator flap. Methods: From January 2017 to December 2018, 6 patients with defect of over length or large size were repaired with free perforator flaps, anterolateral thigh(ALT) flap in 3 cases and deep inferior epigastric artery perforator(DIEP) flap in 3 cases in Department of Hand Surgery, Ningbo No.6 Hospital. There were 4 males and 2 females, aged from 29 to 54 years old, with an average age of 41 years old.It was found that the size of the flap beyond the perforasome, while multiple perforators in the flaps were not from the same pedicle. The turbocharging technique was applied in the operation. The distal perforator of the flap was anastomosed with the proximal pedicle branch. The flap size ranged from 20 cm×8 cm to 25 cm×12 cm. The donor sites were closed directly for 3 cases and skin grafting for 3 cases. Results: All the flaps survived successfully, no distal necrosis occurred. The patients were followed up for 3 to 12 months, with an average of 9 months. All flaps survived well with satisfactory appearance and pliable texture. The healing of skin graft was satisfactory in 3 cases in donor site. No graft skin contracture occurred. The donor sites closed directly in 3 cases had linear scar in donor site, no obvious contracture occurred. The flap sensation returned to S2-S3. Conclusions If the size of the flap is super long or large, beyond the perforasome, while multiple perforators in the flaps were not from the same pedicle, the application of turbocharging technique can avoid partial necrosis of the flap and improve the survival rate of the flap, which is an ideal alternative.

Objective To evaluate the effect of enteral immune nutrition on the occurrence of acute kidney injury(AKI) in sepsis patients. Methods A retrospective study was conducted, 80 patients with sepsis admitted and treated in the intensive care unit (ICU) of Quzhou People's Hospital from January 2015 to December 2016 were enrolled, and according to different treatment programs, they were divided into an immune nutrition group and a standard nutrition group, each group 40 cases. The two groups received an equal amount of calories and nitrogen in enteral nutrition (EN). After treatment, the changes of serum total protein (TP), albumin (Alb), prealbumin (PA), hemoglobin (Hb), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL-6, IL-10), infection site, length of stay in ICU, mortality in ICU, AKI incidence, AKI staging, etc in the two groups were observed. Results ① After treatment, the nutritional indicators TP, Alb, PA, Hb levels were significantly increased, the serum inflammatory factors CRP, TNF-α, IL-6 were obviously decreased and IL-10 was markedly increased in the two groups compared with those before treatment (all P < 0.05), the changes in the immune nutrition group were more obvious than those in the standard nutrition group [TP (g/L): 60.84±5.90 vs. 58.32±6.11, Alb (g/L): 33.95±3.83 vs. 31.79±3.44, PA (g/L): 0.24±0.04 vs. 0.21±0.03, Hb (g/L): 117.47±16.15 vs. 112.50±15.71, CRP (mg/L): 53.04±23.76 vs. 82.33±37.09, TNF-α (ng/L): 20.29±17.74 vs. 29.63±18.43, IL-6 (ng/L): 50.74±28.55 vs. 80.32±31.67, IL-10 (ng/L): 41.09±24.65 vs. 40.86±24.73]; ② The length of stay in ICU (days: 10.54±4.33 vs. 14.80±5.19), ICU mortality [15.00% (6/40) vs. 32.50% (13/40)] and the incidence of AKI [22.50% (9/40) vs. 47.50% (19/40)] of immune nutrition group were significantly lower than those of standard nutrition group (all P < 0.05); There were 9 cases of AKI mainly at stage I andⅡ (8 cases) in the immune nutrition group, while in the standard nutrition group there were 19 cases with AKI mainly at stageⅢ (11 cases). Conclusion The enteral immune nutrition can effectively reduce the incidence of AKI in sepsis patients, and the mechanism may be related to the immune nutritional preparation can inhibit the expressions of pro-inflammatory factors such as TNF-α, IL-6, etc.

Objective To explore the clinical value of the dual-low-dose with low tube voltage for head and neck CTA. Methods One hundred and sixty patients who were clinically suspected head and neck vascular disease underwent CTA procedure were propective selected, and whose body mass index (BMI) was also lower than 25 kg/m2. Forty cases were randomly selected as conventional group(120 kV,150 mAs, iodine 320 mg/ml), the other 120 cases were as the low dose group. The low dose group divided into three subgroups according to the random number table method, which were low iodine group (37 cases;120 kV,150 mAs, iodine 270 mg/ml), low tube voltage group (42 cases;100 kV,150 mAs, iodine 320 mg/ml) and low iodine and tube voltage group (41 cases;100 kV,150 mAs, iodine 270 mg/ml). The carotid bifurcated CT value, standard deviation (SD), signal-to-noise ratio (SNR), iodine intake and effective radiation dose (ED) of the four groups were recorded,all data undertook statistical analysis useing one-way ANOVA. Meanwhile, the subjective image quality score was applied to evaluate the image quality, and the differences among groups were compared by Wilcoxon signed ranks test. Results The image quality score were (2.85±0.19),(2.33 ± 0.34),(2.26 ± 0.32),(2.87 ± 0.22) in the four groups, and there was no statistical difference between groups(P>0.05).The carotid bifurcated CT value were respectively (380±30),(314±27),(514±52) and (425±28) HU in conventional, low iodine, low tube voltage and dual-low-dose groups, and the iodine intake were (18.85±2.10), (15.75±1.78), (18.53±1.98), (15.62±1.92) g, the ED of the four groups were (1.74±0.14), (1.73± 0.11), (1.32 ± 0.08) and (1.35 ± 0.09) mSv, the difference were all statistically significant (P<0.01). Furthermore, the iodine intake and the effective radiation dose in dual-low-dose group were significantly lower than the conventational group. Conclusions Head-and-neck CTA with dual-low-dose scan can provide same quality images as using 100 kV and high dose iodine contrast agent, and which also significantly reduced the ED and iodine intake greatly. Thus, this scanning program has great clinical value.

Objective To observe the survival rate of free flaps and incidence of vascular crisis following the perforator flap transfer in end-to-side microvascular anastomosis compared with the traditional method and investigate the scientificity and practicability of this scheme.Methods From February, 2012 to October, 2013, 152 cases of free flaps (including superficial illiac circumflex perforator flap, lateral arm flap, peroneal perforator flap, and anterolateral thigh flap) were performed.The end-to-side anastomosis were performed in 72 cases while end-to-end anastomosis in 80 cases;All patients were followed up for 6-24 months.The occurrence of vascular crisis in all cases were observed and recorded.The results of the two groups were conducted statistical analyzed.Results The average anastomosis time for end-to-side anastomosis (21.3 ± 3.8 min) was significantly higher than the end-to-end anastomosis (14.4 ± 3.2 min) (P ＜ 0.05).The incidence of anastomotic vasospasm after end-to-side anastomosis (5.6％) was significantly lower than traditional method (16.3％) (P ＜ 0.05).There was no significant difference in the survival rate of the free flaps between the end-to-side anastomosis group (97.2％) and the traditional group postoperatively (96.3％) (P ＞ 0.05).Conclusion Although anastomosis times were increased in the end-to-side group, this technique showed lower spasm rate and similar flap survival rate.Therefore, this technique is a reliable and technically feasible method and should be considered first as a choice when facing vessel discrepancy and for preserving the recipient artery and vein system.