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.

Dermacentor abaensis(D.abaensis)is a tick species distributed only in Qinghai,Gansu,and other provinces of China.It is more harmful because it can carry pathogens such as Borrelia burgdorferi and Piroplasm.However,morphological descriptions and image data for this tick spe-cies are still insufficiently detailed,and data related to molecular markers such as COX 1 and ITS2 are still missing.The ticks were collected from the body surface of yaks in Diebu County,Gannan Tibetan Autonomous Prefecture,Gansu Province.The morphological characteristics of various parts of the ticks were carefully observed using a stereomicroscope ultra-depth-of-field system.At the same time,the total DNA of the tick body wall was extracted,then the primers for COX 1 and ITS2 genes were designed,and PCR amplification was performed before sequencing.The sequen-cing results were compared with related sequences in GenBank for homology analysis,and the phy-logenetic tree was constructed to provide a basis for accurate identification of this tick species.The results showed that the female ticks were subrounded.The basic capituli were rectangular in shape.The porose area was ovoid in shape,cornua short and blunt,palps thick and short,with a slightly pointed front end.A slightly rounded scutum,and the enamel color was slightly lighter towards the back.The cervial groove was short,and in deeply concave.The festoon was obvious.The peritreme was in comma-shaped.The trailing edge was slightly curved.The genital opening had a ala.The anus was located in the posterior quarter of the middle of the abdomen,and there is a semicircular anal groove surrounded.Male ticks were slightly elongated ovoid,with no porose area.The entire surface was covered with enamel color except the cornua.The genital opening was opposite to the coxall,and there is no ala.The anal groove was deeper,and the external spur of the coxa Ⅳ was narrower and longer.All other body characteristics are similar to those of female ticks.Based on the comparative analysis of COX 1 and ITS2 gene sequences and the construction of phylogenetic tree,it was found that D.abaensis is more closely related to Dermacentor nuttalli and Dermacentor marginatus than other Dermacentor spp.The results suggested that D.abaensis have unique mor-phological and molecular marker characteristics,and the combination of the two characteristics will make it easier to rapidly and accurately identify this tick species.

Objective To explore the clinical efficacy of the new transumbilical laparoscopy and the conventional three-port method in the treatment of unilateral huge(≥15 mm)indirect inguinal hernia.Methods A retrospective analysis was conducted on the clinical data of 213 children with unilateral huge(≥15 mm)indirect inguinal hernia admitted to the hospital from July 2020 to August 2023.According to different surgical methods,the children were divided into the three-port group(107 cases,undergoing three-port laparoscopic high ligation of hernia sacs)and the new group(106 cases,undergoing new transumbilical laparoscopic surgery).The surgical indicators of the two groups of children,the face,legs,activity,cry,consolability(FLACC)score,parents'satisfaction with the appearance of the incision,testicular volume,postoperative complications and recurrence rate(within 1 year after surgery)were compared.Results The intraoperative blood loss and the number of incisions in the new group were less than those in the three-port group,while the incision length,operation time,postoperative incision healing time and hospital stay were shorter than those in the three-port group.The differences were statistically significant(P<0.05).At 6,12,24 and 48 hours after the operation,the FLACC score of the new group was lower than that of the three-port group,and the difference was statistically significant(P<0.05).The satisfaction rate of parents of children in the new group with the appearance of the incision was 100.00%,which was higher than 88.79%in the three-port group,and the difference was statistically significant(P<0.05).The volume of the affected testicle in both groups before the operation was smaller than that of the healthy side,and the volume of the affected testicle one year after the operation was larger than that before the operation.The differences were statistically significant(P<0.05).One year after the operation in the new group,there was no statistically significant difference in the testicular volume between the healthy side and the affected side(P>0.05).There was no statistically significant difference in the total incidence of complications and overall recurrence rate between the two groups(P>0.05).Conclusion Compared with the conventional three-port method,the new transumbilical laparoscopic surgery has the characteristics of convenient operation,less trauma,less pain,faster postoperative recovery and a beautiful incision.It has more advantages when applied in the treatment of unilateral huge indirect inguinal hernia≥15 mm.

Dermacentor abaensis(D.abaensis)is a tick species distributed only in Qinghai,Gansu,and other provinces of China.It is more harmful because it can carry pathogens such as Borrelia burgdorferi and Piroplasm.However,morphological descriptions and image data for this tick spe-cies are still insufficiently detailed,and data related to molecular markers such as COX 1 and ITS2 are still missing.The ticks were collected from the body surface of yaks in Diebu County,Gannan Tibetan Autonomous Prefecture,Gansu Province.The morphological characteristics of various parts of the ticks were carefully observed using a stereomicroscope ultra-depth-of-field system.At the same time,the total DNA of the tick body wall was extracted,then the primers for COX 1 and ITS2 genes were designed,and PCR amplification was performed before sequencing.The sequen-cing results were compared with related sequences in GenBank for homology analysis,and the phy-logenetic tree was constructed to provide a basis for accurate identification of this tick species.The results showed that the female ticks were subrounded.The basic capituli were rectangular in shape.The porose area was ovoid in shape,cornua short and blunt,palps thick and short,with a slightly pointed front end.A slightly rounded scutum,and the enamel color was slightly lighter towards the back.The cervial groove was short,and in deeply concave.The festoon was obvious.The peritreme was in comma-shaped.The trailing edge was slightly curved.The genital opening had a ala.The anus was located in the posterior quarter of the middle of the abdomen,and there is a semicircular anal groove surrounded.Male ticks were slightly elongated ovoid,with no porose area.The entire surface was covered with enamel color except the cornua.The genital opening was opposite to the coxall,and there is no ala.The anal groove was deeper,and the external spur of the coxa Ⅳ was narrower and longer.All other body characteristics are similar to those of female ticks.Based on the comparative analysis of COX 1 and ITS2 gene sequences and the construction of phylogenetic tree,it was found that D.abaensis is more closely related to Dermacentor nuttalli and Dermacentor marginatus than other Dermacentor spp.The results suggested that D.abaensis have unique mor-phological and molecular marker characteristics,and the combination of the two characteristics will make it easier to rapidly and accurately identify this tick species.

Objective:To analyze the morphology and molecular biology of Rhodococcus erythropolis isolated from blood culture, and clarify its microbiological characteristics, clinical diagnosis and treatment. Methods:Strain F1069 was isolated and cultured. Then, it was analyzed by morphology, physiological tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS), 16S rRNA gene sequencing, and whole-genome sequencing analysis.Results:The colonies of Rhodococcus erythropolis were light yellow, moist, round, and raised, and had neatly-edged margins after being cultured for 48 h. They could turn orange-red after a prolonged cultivation time. The strain was gram-positive bacillus without spores and was negative in acid-fast staining. The strain was identified as Rhodococcus erythropolis by MALDI-TOF MS, and the result was confirmed by 16S rRNA gene sequencing. The F1069 strain contained the RbpA resistance gene and multiple virulence genes. Conclusions:Cases of Rhodococcus erythropolis infection are rare. The diagnosis of such cases depends on the pathogen detection results, especially molecular biology methods. A definitive diagnosis enables rapid guidance for clinical anti-infection treatment.

Objective To explore the clinical efficacy of the new transumbilical laparoscopy and the conventional three-port method in the treatment of unilateral huge(≥15 mm)indirect inguinal hernia.Methods A retrospective analysis was conducted on the clinical data of 213 children with unilateral huge(≥15 mm)indirect inguinal hernia admitted to the hospital from July 2020 to August 2023.According to different surgical methods,the children were divided into the three-port group(107 cases,undergoing three-port laparoscopic high ligation of hernia sacs)and the new group(106 cases,undergoing new transumbilical laparoscopic surgery).The surgical indicators of the two groups of children,the face,legs,activity,cry,consolability(FLACC)score,parents'satisfaction with the appearance of the incision,testicular volume,postoperative complications and recurrence rate(within 1 year after surgery)were compared.Results The intraoperative blood loss and the number of incisions in the new group were less than those in the three-port group,while the incision length,operation time,postoperative incision healing time and hospital stay were shorter than those in the three-port group.The differences were statistically significant(P<0.05).At 6,12,24 and 48 hours after the operation,the FLACC score of the new group was lower than that of the three-port group,and the difference was statistically significant(P<0.05).The satisfaction rate of parents of children in the new group with the appearance of the incision was 100.00%,which was higher than 88.79%in the three-port group,and the difference was statistically significant(P<0.05).The volume of the affected testicle in both groups before the operation was smaller than that of the healthy side,and the volume of the affected testicle one year after the operation was larger than that before the operation.The differences were statistically significant(P<0.05).One year after the operation in the new group,there was no statistically significant difference in the testicular volume between the healthy side and the affected side(P>0.05).There was no statistically significant difference in the total incidence of complications and overall recurrence rate between the two groups(P>0.05).Conclusion Compared with the conventional three-port method,the new transumbilical laparoscopic surgery has the characteristics of convenient operation,less trauma,less pain,faster postoperative recovery and a beautiful incision.It has more advantages when applied in the treatment of unilateral huge indirect inguinal hernia≥15 mm.

Objective:To analyze the morphology and molecular biology of Rhodococcus erythropolis isolated from blood culture, and clarify its microbiological characteristics, clinical diagnosis and treatment. Methods:Strain F1069 was isolated and cultured. Then, it was analyzed by morphology, physiological tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS), 16S rRNA gene sequencing, and whole-genome sequencing analysis.Results:The colonies of Rhodococcus erythropolis were light yellow, moist, round, and raised, and had neatly-edged margins after being cultured for 48 h. They could turn orange-red after a prolonged cultivation time. The strain was gram-positive bacillus without spores and was negative in acid-fast staining. The strain was identified as Rhodococcus erythropolis by MALDI-TOF MS, and the result was confirmed by 16S rRNA gene sequencing. The F1069 strain contained the RbpA resistance gene and multiple virulence genes. Conclusions:Cases of Rhodococcus erythropolis infection are rare. The diagnosis of such cases depends on the pathogen detection results, especially molecular biology methods. A definitive diagnosis enables rapid guidance for clinical anti-infection treatment.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

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.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.