ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

A retrospective case review was conducted of 3 cases with umbilical venous catheterization(UVC) related pericardial effusions in the Neonatal Intensive Care Unit of Zhongnan Hospital of Wuhan University from December 2020 to April 2022.All 3 cases were preterm infants with gestational ages of 33 + 4, 31 and 27 + 6 weeks, respectively.UVC was inserted routinely in 24 hours after birth.Three neonates developed tachycardia or bradycardia, dyspnea, decreased oxygen saturation and muffled heart sound at the 1 st to 4 th day after catheterization.Echocardiography indicated pericardial effusion, so the 3 neonates underwent pericardiocentesis and drainage.Among the 3 neonates, 2 cases improved and have good prognosis, 1 case died.UVC can cause pericardial effusion, which occurs mostly in the early stage after catheterization.Pericardial effusion and tamponade should be considered when patients show unexplained sudden clinical deterioration after catheterization, such as dyspnea, cyanosis, tachycardia or bradycardia, etc.Once diagnosed, umbilical vein catheter should be removed in time and pericardiocentesis and drainage should be performed for decompression.Early diagnosis and intervention can effectively improve the prognosis.

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Heart Valve Diseases ; Heart Valve Prosthesis ; Humans ; Hypereosinophilic Syndrome/complications* ; Mitral Valve ; Thrombosis/etiology*