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 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.

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 investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF).Methods:This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality.Results:The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR=1.28, 95% CI 1.01-1.61, P=0.038), cardiovascular mortality ( HR=1.48,95% CI 1.10-2.00, P=0.010), cardiovascular hospitalization ( HR=1.67,95% CI 1.35-2.07, P=0.008) and the composite endpoints ( HR=2.02,95% CI 1.71-2.38, P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR=1.44,95% CI 1.05-1.98, P=0.025), cardiovascular hospitalization ( HR=1.44,95% CI 1.09-1.90, P=0.010) and the composite endpoints ( HR=1.37, 95% CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR=2.56,95% CI 1.44-4.54, P=0.001). Conclusion:Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

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 study the estimated value of general pituitary hormone levels and "overall levels of pituitary hormone" in patients with pituitary adenoma.Methods Sixty-six patients presented with non-function pituitary adenomas,admitted to our hospital from January 2009 and April 2013,were chosen in our study.Pre-and post-operative hormonal levels and MR imaging data were collected.Patients were divided into two groups:macroadenoma (1 cm＜diameter＜3 cm) group and huge adenoma (diameter＞3 cm) group,and the patients were divided into subtotal resection group (resection rate＞60％) and partial resection group (resection rate＜60％).Self-made scale of "overall levels of pituitary hormone" was performed to assess the remnant pituitary function.The levels for 6 kinds of pituitary hormones and "overall levels of pituitary hormone" were compared between each two groups.Results (1) The levels of 6 kinds of pituitary hormones between the macroadenoma group (n=38) and huge adenoma group (n=28) showed no significant difference before surgery (P＞0.05);the per-operative "overall levels of pituitary hormone" were statistically different between the macroadenoma group (19.59±2.71) and huge adenoma group (18.07±2.00,P＜0.055);there were 13 patients (34.2％) from macroadenoma group and 17 (60.7％) from huge adenoma group having one or more kinds of pituitary hormones lower than normal levels,with significant difference (P＜0.05).(2) The levels of 6 kinds of pituitary hormones between subtotal resection group (n=57) and partial resection group (n=9) showed no significant difference after surgery (P＞0.05);the post-operative "overall levels of pituitary hormone" in the subtotal resection group were significantly higher than those in the partial resection group (P＜0.05);there were 34 patients (59.6％) from subtotal resection group and 2 (22.2％) from partial resection group having one or more kinds of pituitary hormones lower than normal levels,without significant difference (P＜0.05).Conclusions The "overall levels of pituitary hormone",in which 6 kinds of pituitary hormones are seen as a whole,can assess the remnant pituitary function in pituitary adenoma patients more accurately than evaluation of the 6 kinds of pituitary hormone levels separately.

Objective To explore the effect of nonfunctioning pituitary adenoma (NFPA)apoplexy on growth rate of residual tumor after transsphenoidal operation.Methods The follow-up MR imaging data of 57 patients with NFPA who had residual tumors after transsphenoidal operation,admitted to our hospital from May 2005 to May 2015,were analyzed retrospectively.The tumor volume doubling time (TVDT) of residual tumors,rapid growth rate and apoplexy/tumor size ration were calculated.The relations of tumor rapid growth rate with existence of adenoma apoplexy,course of adenoma apoplexy and apoplexy/tumor size ration were compared.Results There were 30 patients with NFPA apoplexy and 27 without adenoma apoplexy.Postoperative follow-up indicated enlarged residual tumors in 49 patients,and shrank ones in 8 patients.The mean TVDT was (1305.82±1685.32) d.The rapid growth rate of residual tumors in NFPA apoplexy group (56.67％) was not significantly increased as compared with that in non-NFPA apoplexy group (66.67％,P＞0.05).The rapid growth rate of subacute NFPA apoplexy group (81.82％) was significantly higher than that of chronic NFPA apoplexy group (36.84％,P＜0.05).The rapid growth rate of group of apoplexy/tumor size ration less than 12％ (40％) was not significantly different as compared with that of rapid growth rate of group of apoplexy/tumor size ration more than 12％ (66.67％,P＞0.05).Conclusions Adenoma apoplexy is one of the factors that affect the growth rote of residual tumors ofNFPA after transsphenoidal operation.For patients with NFPA apoplexy in subacute or chronic phase,if their symptoms are mild,they can be followed up regularly.

Objective Identify the mechanism of induced atrial arrhythmias after pulmonary vein isolation (PVI) in patients with paroxysmal atrial ifbrillation(PAF), and investigate its long-term prognosis. Methods All patients with PAF undergoing PVI and induction test afterwards between Feburary 2010 and October 2010 were included. The induction protocol was rapid pacing initiated at cycle length of 250 ms with progressive shortening in a decrement of 10 ms down to 180 ms or refractoriness. Isoproterenol of 2-4μg/min was administrated as well. Inducibility was deifned as induction of atrial arrhythmia lasting >1 min. The mechanism of induced tachycardia was identiifed by activation mapping and entrainment mapping under the guidance of CARTO system. All patients were followed up by 36 months. Results Forty-nine atrial tachycardia were induced in 39 (19.7%) patients, including 35 organized atrial tachycardia (OAT) and 14 atrial ifbrillation (AF). The LA diameter was signiifcantly larger in inducible group than non-inducible group (39.5±6.6 mm vs. 36.7±5.2 mm, P=0.004). Macroreentry was the most common mechanism in induced OATs (28, 80.0%), and mitral isthmus was the most common critical site (20, 40.8%), followed by cavo-tricuspid isthmus (12, 24.5%), PV (6, 12.2%), LA septum (4, 8.2%), superior vena cava (3, 6.1%) and LA roof (1, 2.0%). Conclusions The most common mechanism of induced tachycardia by IV isoproterenol and rapid pacing is MI and CTI dependent after PVI in PAF patients, which can be succssefully eliminated by liner ablation, not increasing long-term recurrence rate.

Objective To identify the electrophysiological charateristics and cause of ridge gap related reentry after MI ablation in atrial ifbrillation patients. Methods Activation and entrainment mapping was performed in 82 redo cases for OAT recurrence in whom MI was ablated during the index produre. Once ridge gap related reentry was conifrmed, detailed mapping was performed in MI and ridge region. In addition, in 36 cases undergoing MI ablation and fulfilling criterion for bidirectional block, differential pacing was repeated at the ridge to identify a ridge gap. Results Out of 82 redo cases for OAT recurrence in whom MI was ablated during the index produre, 7 (8.5%) was found to be ridge gap related reentry. TCL was (247.9±19.2) ms, and the left atrial endocardial activation time was (145.4±17.7) ms, accounting for (58.5±3.2)%of TCL. However, wide double potential was recorded along the previous ablated MI line where PPI was (34.3±6.6) ms longer than TCL, while PPI was signiifcantly shorter at the ridge[PPI-TCL (11.4±3.9) ms, P<0.001]. Tachycardia was terminated at the ridge in 6 cases and at the corresponding site in coronary sinus in 1 case. No recurrence was found during follow-up for (11.1±4.5) months. In addition, in 36 patients undergoing MI ablation in whom criterion of bi-directional block was fuliflled, conduction gap located at the ridge was found in 5 (13.9%) cases. Conclusions MI ridge gap related reentry is a distinctive OAT, in which the ridge was used as the critical isthmus, whereas the previous ablated MI line is not part of the reentry. MI pseudo-block due to the ridge gap may lead to this type of recurrent tachycardia.