Objective To compare the clinical characteristics of cirrhosis with or without portal vein thrombosis(PVT),and to analyze the therapeutic effect of transjugular intrahepatic portosystemic shunt(TIPS)in treating cirrhosis with or without PVT.Methods The clinical data of 193 patients with cirrhosis complicated by gastrointestinal bleeding,who received TIPS from October 2018 to October 2022,were retrospectively analyzed.According to the presence or absence of PVT before TIPS,the patients were divided into non-PVT group(n=118)and PVT group(n=75).After TIPS,the patients were followed up at one,3,6 months and every 6 months thereafter.The effect of PVT on the clinical characteristics of cirrhosis patients and on the therapeutic efficacy after TIPS were analyzed.Results The success rate of TIPS was 100％in both groups.The proportion of carrying out splenectomy or partial splenic artery embolization(PSE)in PVT group was 26.7％(20/75),which was obviously higher than 13.6％(16/118)in non-PVT group,the difference between the two groups was statistically significant(x2=5.192,P=0.023).In PVT group the preoperative Child-Pugh score,the model of end-stage liver disease(MELD)score and serum sodium model of end-stage liver disease(MELD-Na+)score were(8.1±1.9)points,(9.2±8.0)pointsand(9.2±8.0)points respectively,which in non-PVT group were(7.4±1.9)points,(7.7±5.8)points and(7.7±5.8)points respectively,the differences between the two groups were statistically significant(all P＜0.05).The incidence of overt hepatic encephalopathy in PVT group was 33.3％(25/75),which was strikingly higher than 19.5％(23/118)in non-PVT group,the difference between the two groups was statistically significant(P=0.030).No statistically significant differences in postoperative survival rate,rebleeding rate and stent dysfunction rate existed between the two groups(all P＞0.05).Conclusion For the treatment of cirrhotic patients with PVT complicated by gastrointestinal bleeding,TIPS is clinically safe and effective.In cirrhotic patients with PVT,the worse the liver function is,the higher the incidence of overt hepatic encephalopathy after TIPS will be.

Objective To compare and analyze the clinical characteristics and efficacy of transjugular intrahepatic portosystemic shunt(TIPS)in the treatment of liver cirrhosis with different portal vein thrombosis(PVT)grades.Methods A retrospective analysis was performed on 75 patients with liver cirrhosis and gastrointestinal bleeding who received TIPS.According to the Yerdel scale of PVT,the patients were divided into type Ⅰ(34 cases),type Ⅱ(25 cases)and type Ⅲ(16 cases).The patients were followed up 1,3,6 months after TIPS and every 6 months thereafter to compare the clinical data and the efficacy of TIPS in three types of PVT patients.Results The success rate of TIPS in three types of patients was 100％.There were differences in platelet to lymphocyte ratio(PLR)and proportion of different Child-Pugh grades among the three types of patients(P＜0.05).After TIPS,portal vein pressure was decreased compared with that before TIPS(P＜0.001).However,there were no significant differences in postoperative survival rate,rebleeding rate,over hepatic encephalopathy rate,stent dysfunction rate,thrombus complete recanalization rate and thrombus recurrence rate(P＞0.05).Conclusion The success rate of TIPS in three types of patients is higher,and the portal vein pressure is decreased significantly after TIPS,but there are no significant differences in the postoperative efficacy.Although the implementation of TIPS in cirrhotic PVT patients is challenging,it is still worth the effort to reshape the portal vein for the benefit of patients.

Objective To investigate the effect of altered oxidative stress system on liver function after partial splenic embolization(PSE).Methods Twenty-nine patients with liver cirrhosis and hypersplenism who received PSE were selected.Peripheral venous blood was drawn from the patients before and at 1 week,1 month,and 3 months after PSE,and the indexes of oxidative stress system factors including malondialdehyde(MDA),superoxide dismutase(SOD),advanced oxidiation protein products(AOPPs),and gluta-thione peroxidase(GSH-Px)were detected,as well as liver function indexes.Results There were positive correlation between SOD activity and total bilirubin(TBil)and model for end-stage liver disease(MELD)scores at 1 week postoperatively(TBil:r=0.725,P＜0.05;MELD:r=0.764,P＜0.05).There was positive correlation between GSH-Px activity and alanine aminotransferase(ALT)at 1 month postoperatively(r=0.777,P＜0.05),however,the AOPPs was negatively correlated with ALT and aspartate aminotransferase(AST)at 3 months postoperatively(ALT:r--0.900,P＜0.05;AST:r=-0.957,P＜0.05).Conclusion PSE can improve the body oxidative stress system and enhance the body's antioxidant response,and then improve the liver function.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

  Objective  Myocardial fibrosis is a potential mechanism of light-chain myocardial amyloidosis(AL-CA). This research aimed at exploring the correlation between multiparameter cardiac magnetic resonance (CMR) and myocardial fibrosis by relating the CMR myocardial tissue characteristics, the morphological and the functional parameters with gallium-68-labeledfibroblast activation protein inhibitor 04 positron emission tomography (⁶⁸Ga-FAPI PET).  Methods  We gave the patients diagnosed with AL-CA in Peking Union Medical College Hospital from August to December 2021 the examinations of CMR and ⁶⁸Ga-FAPI PET/CT. We recorded and analyzed the information on clinical manifestations and examinations of the patients.  Results  A total of 23 patients with AL-CA were included, 15 (65.2%)of which were male and the mean age was 58.3±6.5 years. Patients with high ⁶⁸Ga-FAPI-04 uptake had shown growth in myocardial extracellular volume (ECV), significantly higher than those in the negative group (P=0.047). In addition, patients' myocardial ECV was positively correlated with myocardial FAPI uptake (r=0.628, P=0.001;r=0.727, P < 0.001;r=0.661, P=0.001). Patients in the positive group showd reduced left ventricular (LV) ejection fraction (EF)(P < 0.001).LVEF (r=-0.798, P < 0.001;r=-0.794, P < 0.001; r=-0.795, P < 0.001) and right ventricular (RV)EF (r=-0.735, P < 0.001;r=-0.739, P < 0.001;r=- 0.684, P < 0.001) showd negatively correlated with myocardial FAPI uptake, LV circumferential strain (r=0.668, P < 0.001;r=0.708, P < 0.001;r=0.705, P < 0.001), LV longitudinal strain (r=0.629, P=0.001;r=0.635, P=0.001; r=0.597, P=0.003), and RV longitudinal strain (r=0.575, P=0.004; r=0.792, P < 0.001;r=0.673, P < 0.001) were negatively correlated with myocardial FAPI uptake.  Conclusions  FAPI-related fibroblast activation is concurrent with CMR-related abnormal myocardial interstitial characteristics that leads to the decreased function of the myocardial movement. Patients with increased FAPI uptake present with increased ECV, decreased EF, and decreased strain with morphological abnormalities.

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

Objective To make classification and segment measurement for the cases with tibiofibular and ankle fractures in parachuting landing, and investigate main classification types of parachuting fractures and fracture segments of high risk.Methods A total of 56 fracture cases in parachuting landing were collected, and the tibiofibula and ankle fractures were classified according to AO-OTA or Lauge-Hansen classification standards respectively based on their digital X-ray images. The medium plane between talus and tibia joint planes in ankle joint was defined as the reference plane. The highest and lowest injury points of tibia and fibula were marked respectively, and the fracture segment was defined between the highest and lowest point for statistical analysis.Results For tibiofibular and ankle fracture cases in parachuting landing, fracture at both tibia and fibula accounted for 80.4%. The major classification of tibiofibula fracture was 42-D/5.2 (45.8%) and 42-D/5.1 (16.7%). The major classification for ankle fracture was pronation-external rotation (PER, 59.4%) and supination-external rotation (SER, 37.5%). When tibiofibular and ankle fracture cases in parachuting landing occurred, the fracture segment of the tibia was mainly from 57 to 143 mm above the reference plane and from 6 mm below the reference plane to 24 mm above the reference plane, while the fracture segment of the fibula was 4-45 mm and 74-83 mm above the reference plane. Injury risks of all above segments were higher than 50%.Conclusions For protection of lower limbs in parachuting landing, the fracture at both tibia and fibula should be highly noticed. The ankle motion of PER and SER should be especially restricted in parachuting ankle protection.

The number of combination products is increasing, and the cutting-edge and innovative technologies are constantly being used. How to evaluate combination products become difficult points. This study team summarizes the supervision conditions of the combination products and analyzes the common problems of these products application from the perspective of technical review, in order to provide reference for Chinese manufacturers and investigators in these products registration.
Biomedical Technology

Neurofibromatosis type 1 combined with giant neurofibroma is very rare, and treatment is quite difficult. October 2019, a 23 year-old female patient of neurofibromatosis type 1 combined with giant neurofibroma at the shoulder and back was treated at the Department of Burn and Plastic surgery, the First People’s Hospital of Bijie Municipal. The giant neurofibroma was resected and the skin from the tumor surface was replanted to cover the wound. During the following period of 3 months, satisfactory results were achieved for both donor site and recipient site.

Neurofibromatosis type 1 combined with giant neurofibroma is very rare, and treatment is quite difficult. October 2019, a 23 year-old female patient of neurofibromatosis type 1 combined with giant neurofibroma at the shoulder and back was treated at the Department of Burn and Plastic surgery, the First People’s Hospital of Bijie Municipal. The giant neurofibroma was resected and the skin from the tumor surface was replanted to cover the wound. During the following period of 3 months, satisfactory results were achieved for both donor site and recipient site.