Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Objective:To evaluate the imaging features of CT scan in patients with COVID-19.Methods:Clinical data of 56 patients with COVID-19 from January 17 to 19, 2020 admitted to Wenzhou Central Hospital and the Second Affiliated Hospital of Wenzhou Medical University were retrospectively reviewed. The clinical manifestations, lung imaging characteristics and treatment outcomes of patients with different severity were analyzed with SAS software.Results:Fever (92.8%, 52/56), dry cough (75.0%, 42/56) and asthenia (58.9%, 33/56) were the first symptoms in most of the patients; some patients also had shortness of breath (25.0%, 14/56) and pharyngeal pain (10.7%, 6/56). Chest high-resolution CT scan showed that in 42 moderate patients, ground glass-like high-density shadows in the lung were observed in 30 cases (71.4%) ; localized plaque consolidation shadows and bronchial inflation signs were observed in 10 cases (23.8%). In 12 severe patients, 11 had high-density patches involving multiple lung lobes (≥3). In 2 critically ill patients the patches and stripes involving the entire lung were observed; and cord-like high-density shadow, local consolidation and fibrosis were also shown.Conclusion:The multiple ground-glass changes outside the lungs are early imaging manifestations of COVID-19 patients. The increase in pulmonary lobe consolidation and fibrosis may indicate the disease progression, and the degree of lung consolidation and fibrosis is closely related to the disease severity.

Objective: To summarize the clinical anatomical features and surgical technique of the submental artery perforator flap (SMAPF), and to evaluate the outcome and value of the flap for oral cavity reconstruction after cancer ablation. Methods: A total of 56 patients with oral cancer were included in this study. The modified SMAPF excluded the anterior belly of the digastric muscle and submental fatty tissue. The primary sites of malignancy were buccal mucosa (n=24), tongue (n=21), mandibular gingiva (n=6), mouth floor (n=3), soft palate (n=2). Results: The flap size varied from 3 cm×5 cm to 5 cm×12 cm. Four flaps presented mild venous congestion, which was salvaged with conservative measures such as acupuncture and blood letting. Overall flap survival rate was 100%. The SMAPF with septocutaneous perforator was used in 49 cases and with musculocutaneous perforator in seven cases. External jugular vein and internal jugular vein provides venous drainage were applied in half cases respectively. All the patients showed a good recovery of tongue mobility and mouth opening with a follow-up of 3-41 months. Local recurrence was detected in one patient 4 months after operation. Conclusions The SMAPF is a reliable flap for oral cavity reconstruction with outstanding functional and aesthetic outcomes.

Objective To evaluate the clinical repair effects of the reconstruction of different vermilion tubercle after primary cleft lip repair.Methods According to the tight lip deformity and dif ferent degrees of defect of the vermilion tubercle and exposing the gums and the crown of the anterior incisors,178 patients after primary repair of the cleft lip from Department of Oral and Maxillofacial Surgery of Xiangya Hospital,Central South University were classified into the tight lip deformity and four grades of whistling deformities.According to different deformities and defects,the different operative techniques were used as follows:classic Abbé flap and modified Abbé flap were used for tight lip deformity;the bilateral advanced myomucosal flaps of lip were used for the grade Ⅰ;modified Abbé flap was used for repairing the grade Ⅱ and the grade Ⅲ whistling deformities;for grade Ⅳ whistling deformity,we mainly used classic Abbé flap.The follow-up after operation was performed,all patient's Cupid's bow,Cupid's bow peak,the vermilion tubercle and the height and width of the upper lip were observed.The scarring of the upper lip was also observed.Results The follow-up after operation was performed from six months to ninteen years,all the 187 patient's anatomical structures of the upper lip were nearly normal after recovery.The all patients showed an obvious Cupid's bow,Cupid's bow peak,the vermilion tubercle and the height and width of the upper lip.The relation of the upper lip and lower lip was harmonious.The scarring of the upper lip was not obvious 2 years after operation.Conclusions The different repair methods are chosen to repair different deformity and defect that has an important clinical value.

Objective To explore the indication,technology and clinical significance of laparoscopic choledocholithotomy and primary suture in treatment of choledocholithiasis.Methods 78 patients with choledocholithiasis were divided into two groups receiving respectively laparoscopic choledocholithotomy and T-tube drainage treatment,and laparoscopic choledocholithotomy and primary suture after common bile duct exploration.The time of operation,postoperative hospital stay and complications were analyzed and compared.Results Bile leakage occurred in 2 cases in the primary suture group and 3 cases in the T-tube drainage group;No residual stones or biliary stricture was found in either groups.The time of operation,postoperative complications were not statistically different (P ＞ 0.05).The difference in postoperative hospital stay and GI function recovery time between the two groups was statistically significant (P ＜ 0.05).Conclusion In well selected cases,the primary suture of common bile duct after laparoscopic choledocholithotomy is feasible and safe.

Objective:To introduce a new style of platysma myocutaneous flap and to evaluate its application value in the restoration of oral-maxiofacial defects.Methods:Platysma myocutaneous flap with apron incision was used for the restoration of oral-maxiofacial defects after oral lesion ablation in 15 cases from January,2014 to September,2015.The platysma muocutaneous flap was harvested with a U shaped apron incision.The skin above the flap pedicle was preserved.The platysma pedicle was widened to ensure the flap survival.All the patients were followed up form 4 to 33 months.Results:Of the 15 platysma myocutaneous flaps,12 survived completely and 3 had partial flap necrosis.The total survival rate of the flaps at the recipient site of buccal mucosa,tongue and alveolar was 8/9,1/3 and 3/3 respectively.Additionally,there were 2 cases of disturbed wound healing in the neck.Except for 1 case of carcinoma of gingiva which had apparent cervical scar and 1 case of tongue carcinoma which had limited tongue mobility,the other cases showed a satisfactory recovery of oral-maxillofacial contour and fucnction.Conclusion:Compared with the traditional platysma myocutaneous flap,the platysma myocutaneous flap with apron incision can provide a larger skin paddle,and is suitable for the restoration of small and medium sized buccal mucosa and alveloar defects,but not for tongue defect.

Objective To evaluate orthotopic splenectomy and pericardial devascularization for the treatment of portal hypertension.Methods The modified anterior approach splenectomy includes dissection of the peri-splenic vessels and ligments before division of short gastric vessels.During pericardial devascularization,the dessection panel was close to the esophagus and the stomach,leaving intact both the anterior and posterior vagus trunks.Results 63 patients underwent this modified operation.The free portal pressure decreased from (38 ±4) cmH2O to(28 ±4)cmH2O.The average blood loss was (530 ± 37)ml.There was no mortality,nor perioperative gastric paralysis and portal venous thrombosis.By 12-36 months follow-up,there was no pancreatic leakage,hepatic coma and recurrence of bleeding.Intrahepatic portal venous thromboses were detected in 4 cases at the sixth postoperative months.Conclusions This modified splenectomy plus selective pericardial devascularization carries less bleeding and is safe and effective for the treatment of portal hypertension.

Objective To investigate the management of difficult recipient vessel preparation in microsurgical reconstruction for oral and maxillofacial defects with free flaps and to assess the clinical outcome.Methods A total number of 739 patients with oral and maxillofacial defects underwent consecutive free flap reconstruction with 761 free flaps from May,2012 to May,2015.There were 37 patients who could not find or lack of proper recipient vessels for microvascular anastomosis during operation.Among them,22 were recurrent oral cancer after tumor ablation,10 of them undrewent post-operative radiotherapy;5 were second primary oral cancer,7 diagnosed with osteoradionecrosis,and 3 suffered from oral and maxillofacial defect and deformity caused by trauma or inflammation.Forty free flaps including 23 anterolateral thigh flaps (ALT),10 fibular flaps and 7 radial forearm flaps were harvested.Methods and techniques used during the operation,instant patency rate after anastomosis,the overall survival rate of free flaps,and post-operative complications were recorded.Results Ninety-one anastomoses were performed between 87 pairs of vessels in 37 patients.Fifty recepient vessels were located on ipsilateral side of neck,and the most frequently used recipient vessels were those preserved or not being damaged in former operation and radiation,former transferred free flap vascular pedicles and residual ends of the ligated vessels.Thirty-seven recepient vessels were found on the contralateral side of neck.Thirty-one cases of long-pedicle flap harvesting,2 cases of vein and artery grafting,4 cases of vessel transposition,5 cases of phleboplasties,9 cases of end-to-side anastomoses,and 1 case of flow-through technique were applied in recipient vessels preparation alone or in combination.The patency rate of anastomosis during operation was 100％ and the overall survival rate of free flaps was 97.5％.Conclusion Recurrent oral cancer after tumor ablation,second primary oral cancer,osteoradionecrosis and deformity caused by trauma and inflammation are the main reasons of unsuitable recipient vessel conditions in microsurgical reconstruction for oral and maxillofacial defects.Methods including long-pedicle flap harvesting,venous grafting,vessel transposition,phleboplasty,end-to-side anastomosis and flow-through technique applied alone or in combination are still reliable choices for management of neck difficult recipient vessel preparation and anastomosis.

Objective To assess the clinical application value of phleboplasties combined with microvascular anastomotic device in venous anastomosis with diameter discrepancy in head and neck defects reconstruction.Methods Sixty-six pairs of veins with significant diameter discrepancy were anastomosed in head and neck reconstructive surgeries with free flaps.Forty of them were anastomosed with microvascular anastomotic device (the coupler group) after phleboplasties including lateral incision, Y-T enlargement and wedge excision while the other 26 pairs of veins were conventionally sutured (the sutured group).Diameter of each vein, anastomosis time, post-operative vascular crisis, flap survival and complications related to the microvascular anastomotic device were recorded.Results The average anastomosis time of the coupler group was (4.78 ± 1.14) min for lateral incision, (5.16 ± 2.07) min for Y-T enlargement and (11.09 ± 3.21) min for wedge excision, and all of them were significantly shorter than that of the sutured group.In the sutured group, all flaps survived except for 2 veins with poor blood flow were cut and re-anastomosed during the operation;1 flap with venous crisis within 72 hours after the operations was explored and replaced with the pectoralis major myocutaneous flap.All veins in the coupler group were successfully anastomosed in a single coupling procedure without anastomotic impatency, blood leak, vessel tearing and ring shedding.No vascular crisis occurred postoperatively.One patient underwent cervical haematoma 5 hours after the operation, and the flap blood supply was unaffected after the haematoma was removed.All flaps in the coupler group survived completely.Patients in both two groups were followed up 6 to 18 months.All flaps healed perfectly and no obvious surgical complications or microvascular anastomotic device rejection happened.Conclusion When anastomoses are carried out using microvascular anastomotic device between veins of different size, phleboplasties including lateral incision., Y-T enlargement and wedge excision can not only reduce the size discrepancy and the anastomosis time, but also ease the difficulty level and guarantee the patency of the venous anastomoses.Wedge excision enjoys the advantage of haemodynamics, and obstruction of venous reflux hardly occurred for size reduction.It should be considered preferentially when external jugular veins are used as the anastomotic vein of the recipient sites in head and neck reconstruction.

OBJECTIVETo evaluate the feasibility and outcomes of chimeric deep circumflex iliac artery perforator flap (DCIAPF) applied in the simultaneous reconstruction of the oromandibular defect.

METHODSSix patients underwent simultaneous oromandibular reconstruction using DCIAPF following segmental mandibulectomy in Xiangya Hospital from March 2014 to July 2014. The skin paddle was designed to be centered on the pre-operative perforator mapping. Retrograde dissection was performed through the underlying abdominal wall to raise the skin paddle. The pedicle was isolated from the groin, and the iliac crest was cut. The deep iliac circumflex vessels were dissected until the skin paddle was reached. Finally, the donor site was strictly sutured layer by layer to avoid ventral hernia.

RESULTSThe skin paddles ranged from 3.5 cmx5.0 cm to 7.0 cmx 10.0 cm. The length of the bone components was 5.0 cm to 11.0 cm. All donor sites closed primarily without skin grafting. DCIAPF was harvested successfully in five patients, except for one patient whose perforator originated from the superficial iliac circumflex vessels. An additional pair of anastomoses was performed. All iliac flaps survived. However, slight skin-edge necrosis and exfoliation caused by flap thinning occurred in one patient and healed after pruning and dressing change. The heights of all alveolar ridges were significantly restored, and no serious donorsite complication was observed during the three to six months' follow-up.

CONCLUSIONDCIAPF is a reconstructive option for mandibular defects because of its adequate bone tissue and rich blood supply. Satisfactory alveolar ridge restoration greatly facilitates future denture retention. DCIAPF also has a great degree of mobility between the skin paddle and the bone component when appliedin composite oromandibular defect reconstruction.

Humans ; Iliac Artery ; Ilium ; Mandible ; surgery ; Maxillofacial Abnormalities ; surgery ; Perforator Flap ; Reconstructive Surgical Procedures ; methods ; Skin