Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To explore the strategy of how to select an effective flap for reconstruction of the surgical defect in clavicular region after resection of malignant tumour and care for the aesthetic appearance of the flap donor site.Methods:A retrospective observational study was conducted. Twenty-three patients with soft tissue malignant tumour in clavicle region were treated, from March 2017 to April 2023, in the Department of Burn and Plastic Surgery of Changde Hospital, Xiangya School of Medicine, Central South University (the First People’s Hospital of Changde). The patients were 13 males and 10 females, aged 21 to 72 years old. Ten patients were of dermatofibrosarcoma protuberans, 6 of fibrosarcoma, 3 of squamous cell carcinoma of skin, 3 of undifferentiated pleomorphic sarcoma and 1 of mucinous adenocarcinoma. Nine patients had the first surgery and 14 were with tumour recurrence and had previousely received one or more surgery in other hospitals. The tumour size ranged from 2.0 cm×4.5 cm×1.0 cm to 10.0 cm×16.0 cm×3.0 cm. After radical resection, the sizes of surgical defect ranged from 9.0 cm×12.0 cm to 16.0 cm×22.0 cm. All the clavicular soft tissue malignancies had radical resection, and the secondary surgical defects were further modified to reduce the short and long dimensions of the defects. Flaps were selected according to the short dimension, depth and skin elasticity of the flap donor site. Of the 23 patients, 3 were treated with free inguinal flaps, 9 with ipsilateral pedicled latissimus dorsi flaps or thoracodorsal artery perforator flaps, 5 with free deep inferior epigastric artery perforator flap (DIEPF), 5 with free anterolateral thigh flap (ALTF) and 1 with free rectus abdominis flap. The modified defects sized 5.0 cm × 11.0 cm-12.0 cm×19.0 cm after the suture of margin and base of the defects (defects were reduced and modified). The flap sizes were 7.0 cm×13.0 cm-14.0 cm×23.0 cm. After surgery, the wound healing was observed through the visits of outpatient clinic, and telephone and WeChat interviews. According to the nature of the tumours, the patients were regularly reviewed at outpatient clinic to determine the local recurrence and metastasis of the tumour.Results:One pedicled latissimus dorsi myocutaneous flap was found with a greater tension after surgery. After partial removal of sutures and dressing changes, the secondary suture was performed 1 week later and the wound healed smoothly. A postoperative venous crisis was discovered in a free ALTF. It was monitored and re-anastomosed within 24 hours after surgery, and the flap survived and the wound healed smoothly. Otherwise, the rest of flaps achieved good blood supply and the wounds at the recipient and donor sites healed in one stage. In the postoperative follow-up, all flaps in the clavicular region were found good in appearance with no obvious swelling, and the donor sites healed well without scar contracture or dysfunction. One patient with a squamous cell carcinoma died of lung metastasis at 13 months after surgery. The rest of patients were found no tumour recurrence and had completed postoperative follow-up.Conclusion:After radical resection of malignant soft tissue tumours in the clavicular region, appropriate flaps were selected according to the size (short diameter) and depth of the modified defects, as well as the skin elasticity and relaxation of the flap donor site, hence to facilitate the direct suture of the flap donor site. It not only effectively reconstructs the surgical defect in clavicular region, but also minimises the damage to the flap donor site and achieves an aesthetic appearance at the flap donor site.

Objective:To explore the repair methods and effects of refractory wounds in patients after spinal internal fixation operation .Methods:The study was a retrospective observational study. From November 2020 to October 2023, 10 patients with refractory wounds after spinal internal fixation operation were admitted to the Department of Burns and Plastic Surgery of Changde Hospital of Xiangya School of Medicine of Central South University. They were 3 males and 7 females, aged 35 to 68 years. There were 6 cases of thoracolumbar tuberculosis, 3 cases of thoracolumbar fracture, and 1 case of recurrent sacrococcygeal chordoma with skin, soft tissue, and bone defects after radical resection. The wound areas after debridement were 6.0 cm×1.5 cm to 27.0 cm×6.5 cm. The wound repair operation was decided to perform in the primary stage or in the secondary stage according to the wound situation. Two patients with type Ⅰ wounds were treated with debridement, direct suture, and continuous irrigation and drainage with catheter after operation. Eight patients with type Ⅱ wounds were repaired with local flaps (including rotation flap with dermis-fat flap at the end), muscle flaps, or muscle flaps combined with local flaps. The flap sizes were 10.0 cm×5.0 cm to 27.0 cm×14.0 cm, and the sizes of muscle flap were 8.0 cm×5.0 cm×4.0 cm to 17.0 cm×9.5 cm×2.0 cm. The wounds in flap donor areas were sutured directly. The wound treatment methods of patients with type Ⅱ wounds were recorded. The wound healing was observed after operation. The infection and recurrence of wounds, the retention of internal fixation materials, and spinal motor function were observed during follow-up.Results:Among patients with type Ⅱ wounds, there were 3 cases applied with local flaps (including 1 case with rotation flap with dermis-fat flap at the end), 3 cases with muscle flaps (including 1 case with latissimus dorsi muscle flap and 2 cases with erector spinal muscle flaps), and 2 cases with muscle flaps (1 case with latissimus dorsi muscle flap and 1 case with erector spinal muscle flap) combined with local flaps. Only 1 case with secondary defects after radical surgery of sacrococcygeal chordoma had poor wound healing which healed after dressing change, and the wounds of the remaining 9 cases all healed well. During the follow-up of 4 to 18 months, no infection or recurrence of local wounds developed in 10 patients, the internal fixation materials were not loosening, and there was no significant limitation in spinal motor function.Conclusions:For refractory wounds after spinal internal fixation operation, according to the wound type of patients, debridement, suture, irrigation, and drainage in the primary stage, or transplantation of local flaps, muscle flaps, muscle flaps combined with local flaps are performed in the primary stage or in the secondary stage. These methods are proved to have reliable therapeutic effects, not only repairing the wounds, but also retaining the internal fixation materials.

Objectives: This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods: We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients′ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m²) and weight uncontrolled group (ΔBMI≥-1 kg/m²), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months′ follow-up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results: There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1-year follow-up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate (OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

Objectives This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients′ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m2) and weight uncontrolled group (ΔBMI≥-1 kg/m2), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months′ follow?up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin?converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1?year follow?up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate ( OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

Objective To investigate associations of herpes simplex virus(HSV)infection with elevated high-sensitivity C-reactive protein(hsCRP)level and the development of atrial fibrillation(AF) in elderly individuals.Methods Through screening a total of 2,603 individuals,49 patients aged 60 years or over with AF and without structural heart diseases and known risk factors for AF were selected for data collection.Fifty-five elderly healthy control subjects were selected from a population based Chinese Arrhythmia Registry.Baseline characteristics,plasma antibody levels against HSV-1 and-2,and level of hsCRP were analyzed.Results Level of antibodies against HSV-1 was significantly higher in AF patients[(314.5±63.6)mg/L than in control subjects(216.0±50.7) mg/L,P＜0.01].Level of antibodies against HSV-2 was significantly higher in AF patients[(400.1±50.7) mg/L than in control subjects (306.3 ± 64.5) mg/L,P ＜ 0.01].Linear regression analysis demonstrated a positive correlation of plasma levels of hsCRP with both anti-HSV-1 and anti-HSV-2 IgG antibodies (r =0.291,0.188,all P ＜ 0.01).In multiple logistic regression analysis,HSV-1 and HSV-2 antibody levels were significantly associated with AF occurrence(OR =1.035 and 1.034,all P ＜0.01).The optimal cut-off point for predicting AF occurrence was 284.96 mg/L for anti-HSV-1 with sensitivity of 67.3％ and a specificity of 92.7％,and was 366.26 mg/L for anti-HSV-2 with a sensitivity of 67.3％ and a specificity of 85.5％,respectively.Conclusions The increased plasma levels of anti-HSV-1 and anti-HSV-2 antibodies are significantly associated with AF occurrence in elderly adults.

Objective To investigate the clinical effect of cefixime on the treatment for patients with acute bacterial enteritis and the influence on serum inflammatory factors .Methods A total of 92 cases with acute bacterial enteritis ,treated in our hospital from June 2015 to September 2016 ,were selected as the research object ,and randomly divided into cefixime group and cefaclor group , with 46 cases in each group .The cefixime group was given treatment of cefixime ,and cefaclor group was given treatment of cefa-clor ,for 5 to 7 consecutive days .Observation of clinical treatment effect was performed .Results On the first three days after treat-ment ,the number of diarrhea of cefixime group is lower than the one of cefaclor group ,and the difference was statistically significant (P<0 .05);after Day 3 of treatment ,the levels of CRP ,CER ,AAG ,IL-8 ,PCT ,TNF-alpha of cefixime group were lower than those of cefaclor group ,and the difference was statistically significant (P<0 .05);after Day 3 of treatment ,efficiency rate ,effective rate and invalid rate of cefixime group were 50 .0% ,47 .83% and 2 .17% ,respectively ;efficiency rate ,effective rate and invalid rate of cefaclor group were 32 .61% ,56 .52% and 10 .87% respectively ;the treatment effect of cefixime group is better than that of cefaclor group ,and the difference was statistically significant (P<0 .05) .Conclusion The clinical effects of cefixime on the treatment for patients with acute bacterial enteritis is better than that of cefaclor .

Objective The recurrence of perimitral atrial tachycardia is common after initial ablation of persistent atrial fibrillation (AF). The aim of the study is to explore a preferable ablation approach for perimitral atrial tachycardia in the redo ablation of persistent AF. Methods Seventy-four patients with perimitral atrial tachycardia after initial ablation for persistent AF were included in our study. Patients were distinguished into either the group of having ablation during tachycardia (Group A) or the group having ablation after cardioversion to sinus rhythm (Group B) according to the different ablation strategies. The procedural endpoints were pulmonary vein isolation and bidirectional conduction block of all the ablated lines. The primary endpoint of the study was freedom from atrial tachyarrhythmia recurrence during the follow-up period. Results There were statistical differences in baseline clinical data between the 2 groups. During the redo procedure, conduction recovery rate across the mitral isthmus (MI),cavotricuspid isthmus and left atial roofline were 100％, 40.5％ and 48.6％ respectively. The procedural time, fluoroscopy time, mapping time were longer in the patients of group A. During a mean follow-up of (16.9±6.3) months, 31 (72.1％) patients in group A and 21(67.7％) patients in group B maintained in sinus rhythm in the absence of antiarrhythmic durgs (P =0.771) . Conclusion In patients with perimitral atrial tachycardia after initial ablation for persistent AF,ablation in sinus rhythm is a more simplified method and as effective as ablation during tachycardia.

Objective Cryoballoon ablation of pulmonary vein (PV) ostia often induces a vagal response.This prospective study was designed to assess the effectiveness of prophylactic intravenous administration of atropine on hemodynamic impairment induced by cryoballoon ablation in patients with atrial fibrillation.Methods Twenty-five patients with paroxysmal atrial fibrillation undergoing cryoballoon ablation were prospectively enrolled and assigned to either the trial group on the control group.First twelve patients (the trial group) were administered 1 mg of atropine before deflation of the cryoballoon,while the following 13 patients (the control group) were given atropine only after the onset of the hemodynamic variation (decrease in heart rate and/or blood pressure).Treatment was considered effective when the hemodynamic variations were restored.Results In the trial group,three patients with transient hypotension did not require further supportive care throughout the procedures and one patient with hypotension required supportive management.In the control group,hypotension,bradycardia and mixed bradycardia with hypotension requiring supportive care occurred in six,three,and three patients,respectively.Overall,the rate of marked vagal responses was significantly lower when prophylactic atropine was administrated (4/12 vs.12/13 patients,P ＜ 0.01).Conclusions Atropine is effective in the prevention of all types of vasovagal responses induced by cryoballoon ablation in patients with atrial fibrillation.

Objective To investigate ablation characteristics of PVC/VT originating from left ventricle anterior papillary muscles.Methods This study included 10 patients of PVC/VT originating from left ventricle anterior papillary muscles from January 2015 to June 2016 in Beijing Anzhen Hospital.Electrophysiological mapping and radiofrequency ablation were completed using three-dimensional anatomical mapping system combined with three-dimensional intracardiac ultrasound technology.ECG and abaltion target diagram characteristics as well as the special anatomy were explored.Results All the 10 patients were successfully ablated and followed up for 12 months.One patient had recurrence within 12 months and no complications were recorded.The target sites localized at the tip (n =1),middle portion(n =4)or the base (n =5) of the LV-APM.Among 7 patients,the target sites were located at the anterior septal papillary muscle and in 3 patients were located in the free papillary muscle.9 patients were successfully ablated via anterograde trans-septal catheterization after the failure of retrograde approach.Premature QRS wave time were 152.80 ± 11.72 ms and 6 patients presented sharp potential at the targets during PVC/VT.Conclusions PVC/VT originating from left ventricle anterior papillary muscles have similar ECG and diagram characteristics that is different from which originating from left anterior fascicle.It is recommended to get the target via transseptalpuncure approach.Ablation target could be clearly positioned by three-dimensional intracardiac ultrasound technology.