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.

Oral submucous fibrosis (OSF) is a chronic disease that produces scars, tissue fibrosis, and precancerous lesions. Epidemiological studies have shown that chewing betel nut is the most significant risk factor for OSF. Many studies have also indicated that habits such as chewing and smoking tobacco and drinking alcohol increase the risk of OSF, which is widely recognized as an oral precancerous lesion or a potentially malignant oral disorder. Pathological characteristics include chronic inflammation, excessive collagen deposition in the connective tissues below the oral mucous epithelium and local inflammation in the lamina propria or deep connective tissues. OSF patients have a 7%~30% chance of developing oral cancer. Submucosal local injection of triamcinolone and tanshinone was mainly used for the treatment of oral submucosal fibrosis. This treatment improves mouth opening and alleviates the burning sensation in OSF, and the treatment efficacy was as high as 93%. The article will discuss the occurrence, development, diagnosis and treatment of oral submucous fibrosis for clinical management by the medical community.

Oral and maxillofacial/head and neck squamous cell carcinoma (HNSCC), is the sixth most common cancer in the world. To present, management of tumors of the oral cavity and the head and neck has evolved into an increasingly complex specialty , demanding expertise not only in various surgical disciplines, but also in allied specialties such as radiation oncology, medical oncology, endocrinology, nuclear medicine, diagnostic radiology, pathology, and maxillofacial prosthodontics. Surgery has been the mainstay of therapy for cancers in the oral cavity and the head and neck for more than a century. With the introduction of ionizing radiation in the latter half of the 20th century, radiotherapy became an important modality used either independently or in combination with surgery. Although initially chemotherapy was used primarily with palliative intent, it is now used as part of curative treatment approaches when combined with radiation, producing significant responses in patient with squamous cell carcinoma of the oral cavity and the head and neck. Similarly, biological or targeted agents are also evolving to become part of standard therapy. Accordingly understanding and implementing multidisciplinary management strategies are cornerstones for achieving optimal therapeutic outcomes.

Objective:To explore the clinical application and curative effect of brachytherapy of denture applicators with 125I seeds in the treatment of palatal malignant tumor. Methods:Thirty patients with palatal malignant tumor who underwent surgical resection in Shandong Provincial Hospital from February 2012 to January 2020, and brachytherapy was performed with applicator additional 125I seeds 2 weeks after surgery. All patients were followed up for treatment effect and adverse reactions. Results:All patients wore 125I seeds denture base denture applicator well, no 125I seeds displacement and loss. 30 patients had 10-60 months of follow-up, among which 1 patient received palliative treatment with 125I seeds denture applicator alone died after 10 months of follow-up; 1 patient with adenoid cystic carcinoma recurred after 2 years of follow-up and underwent surgical treatment again; the rest patients did not see tumor recurrence or metastasis. The side effects, pronunciation and chewing function were improved in patients ( P<0.05). Conclusions:For patients with palatal malignant tumor, postoperative 125I seeds denture applicator can effectively prevent tumor recurrence and metastasis, reduce complications, and improve the quality of life.

The role of multidisciplinary collaborative diagnosis and treatment (MDT) in improving the prognosis of colorectal cancer, lung cancer, breast cancer and other tumors has been proven, but the research of oral cancer MDT is still in the exploratory stage and has not formed a complete conceptual system and operating mode. Oral squamous cell carcinoma (OSCC) is one of the main malignant tumors of the head and neck, with a 5-year survival rate of less than 50%. This article mainly elaborates on the difficulties of oral cancer treatment, the advantages of MDT, and the progress of oral cancer MDT.

Streptococcus salivarius K12 is a kind of bacteria that settled in the mucosal epithelium of human mouth and nasopharynx shortly after human birth. It is found that Streptococcus salivarius K12 is a probiotic beneficial to human health. Many studies have confirmed that Streptococcus salivarius K12 has bioactive effects against oral and oropharyngeal inflammation and infection, dental caries, halitosis and oral epithelial damage. This paper reviews the research progress of Streptococcus salivarius K12 in the prevention and treatment of oral and oropharyngeal diseases.

Objective:To investigate the application value of totally laparoscopic trans-abdominal-hiatal approach in the radical resection of Siewert type Ⅱ adenocarcinoma of esophago-gastric junction (AEG).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 45 patients with Siewert type Ⅱ AEG who were admitted to the Affiliated Hangzhou First People′s Hospital, Zhejiang University School of Medicine from May 2017 to December 2020 were collected. There were 28 males and 17 females, aged from 35 to 85 years, with a median age of 64 years. All patients underwent radical resection of AEG by totally laparoscopic trans-abdominal-hiatal approach with gastrointestinal anastomosis using proximal gastrectomy with double-tract anastomosis or total gastrectomy with esophagojejunointestinal anastomosis and digestive reconstruction using transdiaphragmatic-hiatal superior overlap esophagojejunostomy. Observation indicators: (1) surgical and postoperative situations; (2) postoperative histopathological examination; (3) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect survival of patients and tumor recurrence and metastasis up to March 2021. Measurement data with normal distribution were presented as Mean± SD and measure-ment data with skewed distribution were presented as M(range). Results:(1) Surgical and post-operative situations: all 45 patients underwent radical resection of AEG by totally laparoscopic transabdominal-hiatal approach successfully, including 35 cases undergoing total gastrectomy with esophagojejunointestinal anastomosis and 10 cases undergoing proximal gastrectomy with double-tract anastomosis. The total operation time, time of lower mediastinal lymph node dissection, time of superior overlap esophagojejunostomy, volume of intraoperative blood loss, time for initial out-of-bed activities, time to first flatus, time to initial liquid diet intake, time to drainage tube removal of the 45 patients were (235±32)minutes, (25±8)minutes, (45±10)minutes, (70±13)mL, (20±8)hours, (2.3±0.2)days, (2.6±0.8)days and (6.2±1.1)days, respectively. Eleven of 45 patients under-went postoperative complications and none of patient died during perioperative period. The post-operative duration of hospital stay of 45 patients was (10±3)days. (2) Postoperative histopatho-logical examination: all 45 patients had negative upper surgical margin. The length of proximal margin, tumor diameter, total number of lymph lodes harvested and number of lower mediastinal lymph nodes harvested were (2.5±0.5)cm, (2.9±0.8)cm, 35.0±4.0 and 2.4±0.8, respectively. Patholo-gical examination showed adenocarcinoma in all 45 patients with pTNM staging as 5 cases of stage ⅠB, 8 cases of stage ⅡA, 21 cases of stage ⅡB and 11 cases of stage ⅢA. (3) Follow-up and survival situations: 45 patients were followed up for 3 to 46 months, with a median follow-up time of 26 months. During follow-up, 8 of 45 patients died. Of the 37 patients survived, 3 cases underwent liver metastasis and 3 cases underwent bone metastasis, lung metastasis or peritoneal metastasis respec-tively.Conclusion:Total laparoscopic transabdominal-hiatal approach is safe and feasible in the treatment of Siewert type II AEG with a satisfactory clinical efficacy.

Objective:To investigate the effect of nurse-led multiple disciplinary team-based intervention in the prevention of venous thromboembolism in paitents undergoing general surgery.Methods:A total of 118 patients who underwent general surgery in the Tianjin First Central Hospital from May 2017 to October 2018 were divided into study group and control group by random digits table method, with 59 cases in each group. The control group received routine thrombosis prevention nursing, the study group carried out nurse-led multiple disciplinary team-based intervention. The condition of lower limbs deep venous hemodynamic was detected by color Doppler ultrasonography at 3 days after surgery, the levels of D-dimer, thrombelastograph coagulation analyzer (TEG) coagulation parameters were also measured at after 24 hours of admission and postoperative day 3, respectively.Results:The vein blood stasis rate was 94.9% (3/59) in the study group, 79.7% (12/59) in the control group, the venous blood flow of the lower 1imbs in the study group was better than that in the control group ( Z value was 2.477, P<0.05). At 3 days after surgery, the levels of D-dimer were (5.26±1.42) mg/L in the study group, (6.36±1.58) mg/L in the control group, D-dimer was decreased in study group compared to the control group, the difference was statistically significant ( t value was 3.991, P<0.05). Coagulation reaction time(R) value and solidification angle(Angel), maximum thrombus intensity(MA), composite coagulation index(CI) levels were (5.30±0.91) min, (69.64±21.93) deg, (65.40±13.76) mm and (1.23±0.20) in the study group, those index were (4.41±0.75) min, (76.64±16.02) deg, (70.98±13.39) mm, (2.09±0.36) in the control group, R value were increased and Angel, MA, CI levels were decreased in the study group compared to the control group ( t value was 2.001-15.997, P<0.05). Conclusions:Nurse-led multiple disciplinary team-based intervention improves the lower limbs deep venous hemodynamic and coagulation function, as well as reduce the incidence of venous thromboembolism.

To evaluate therapeutic effect of combined injection of salvizanolic acid B with triamcinolone acetonide on the treatment of the soft palate with oral submucous fibrosis.
 Methods: Salvizanolic acid B combined with triamcinolone acetonide was consecutively applied once a week for 30 weeks for 33 patients with middle and later periods of oral submucous fibrosis. The response rate of color change in the soft palate and the increase of capillary vessels (determined by degree I-IV visual analog scale) were evaluated at the 12th, 24th, and 36th months after 30 weeks treatment.
 Results: Thirty-three patients were fulfilled the study without obvious adverse reactions and they were followed up for 24 months, while 31 patients were followed up for 36 months. The color change in the soft palatal mucus and the increase of capillary vessels at the 36th month follow-up after treatment were significantly better than those at the 12th month (P=0.004).
 Conclusion: Combined injection of salvizanolic acid B with triamcinolone acetonide in the treatment of the soft palate with oral submucous fibrosis is effective.
Glucocorticoids ; Humans ; Oral Submucous Fibrosis ; drug therapy ; Palate, Soft ; Treatment Outcome ; Triamcinolone Acetonide ; therapeutic use

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.