Ubiquitin-specific protease 1 (USP1) is one of the deubiquitinating enzymes which has received increasing attention in cancer research. USP1 is overexpressed in many types of cancer cells, and has been found to control tumorigenesis and progression by regulating various proteins associated with tumors, such as SIK2, GSK-3β, and Bcl-2. Knockdown or pharmacological inhibition of USP1 can effectively suppress tumors and is also expected to address the issues of cisplatin and poly ADP-ribose polymerase (PARP) inhibitor resistance. This review describes the structure and function of USP1 and the relationship between USP1 targets and tumors and systematically summarizes the structure-activity relationships of small molecule USP1 inhibitors disclosed from 2013 to 2023. Finally, this review discusses the challenges and opportunities in developing small molecule USP1 inhibitors.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

【Objective】To explore the clinical manifestation of COVID- 19 severe cases.【Methods】Clinical data of one severe case with COVID-19 including the clinical characteristic ，laboratory testing results，radiography，treatment，complication and outcome of the patient were retrospectively collected and analyzed.【Results】 The patient with COVID-19 was a 61-year old male，He suffered with underlying disease. His symptoms included fever，cough，myalgia， fatigue，and dyspnea. Laboratory testing results included normal WBC count，decreased lymphocyte cells，elevated LDH and hypoxemia. Radiography findings showed bilateral lung infiltration. His condition deteriorated after intensive treatment for one week. He was intubated and treated with mechanical ventilation because of complicating with severe acute respiratory distress syndrome（ARDS）.【Conclusion】COVID-19 is an emerging acute communicable disease，which lack specific and effective treatment. Most patients have a good prognosis but mortality in severe cases is high. More attention should be paid on the high risk of progression in COVID-19 cases.

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis,which can be done in juvenile rabbits.Passage-four bromodeoxyuridine (BrdU)-labeled ADSCs were cultured,assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability.Two-month-old,healthy male rabbits (1.2 to 1.4 kg,n=45) underwent ischemic induction and were randomly divided into five groups (group A:animal model control;group B:drilling;group C:drilling & ADSCs;group D:drilling & BMP-2;and group E:drilling & ADSCs & BMP-2).Magnetic resonance imaging (MRI),X-ray imaging,hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4,6 and 10 weeks after treatment.Approximately 90％ of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability.Similar results were observed in the rabbits in groups C and E at weeks 6 and 10.The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P＜0.01).Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P＜0.05).In summary,drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

In this study， an endophytic bacteria strain BZJN1 was isolated from Atractylodes macrocephala， and identified as Bacillus subtilis by physiological and biochemical tests and molecular identification. Strain BZJN1 could inhibit the growth of mycelia of Ceratobasidium sp. significantly， and the inhibition rate was more than 70%. The mycelium growth deformity with bulge as spherical and partially exhaustible in apex or central with microscopic observation. The inhibitory rates under 3% and 6% concentrations of the cell free fermentation were 22.7% and 38.7% expectively. The field test proved that the control efficacy of treatment of 1×10⁸ cfu·mL⁻¹ is 75.27% and 72.37% after 10 and 20 days. All the treatments of strain BZJN1 was able to promote the growth of A. macrocephala， the treatment of 1×10⁸ cfu·mL⁻¹ could able to increase the yield to 14.1%.
Atractylodes ; microbiology ; Bacillus subtilis ; physiology ; Basidiomycota ; pathogenicity ; Biological Control Agents ; Endophytes ; classification ; isolation & purification ; Plant Diseases ; microbiology ; prevention & control

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promis-ing anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were rand-omized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium

Acetates ; pharmacology ; Animals ; Disease Models, Animal ; Diving ; adverse effects ; Ear Canal ; injuries ; Nitrogen ; Oxygen ; Protective Agents ; pharmacology ; Rabbits

This study was aimed to evaluate impacts on immune regulation with spleen-strengthening and kidney-tonifying method among advanced malignant tumor patients. The enrolled advanced malignant tumor patients were randomly divided into the control group and the treatment group. The control group was treated with conventional treatment plan. The treatment group was treated with spleen-strengthening and kidney-tonifying Chinese herbs on the basis of conventional treatment plan for three months. Clinical effect, integral of clinical symptom (ICS), T-lym-phocyte subsets, and drug safety index were observed and detected before and after treatment. The results showed that the effective rate and response rate in the control group were 31.1% and 71.1%, respectively. And the effective rate and response rate in the treatment group were 54.2% and 85.4%, respectively. The treatment group was better than the control group (P< 0.05). Compared to the control group, the treatment group had obvious regulation on T-lymphocyte subsets. The improvement on ICS in the treatment group was better than the control group (P < 0.05). There was no obvious adverse reaction with the application of Chinese herbs. It was concluded that the spleen-strengthening and kidney-tonifying method can improve clinical effect, life of quality, and reduce adverse reaction a-mong advanced malignant tumor patients. Its mechanism may be through the regulation of immune function.

Objective To investigate the effect of lipopolysaccharide (LPS) on the expression of cycloxygenase-2 (COX-2) in human bronchial epithelial cells (BEAS-2B),and the role of p38 mitogen-activated protein kinase (MAPK) signal pathway in the expression of COX-2 induced by LPS.Methods Human BEAS2B cells were treated for 2 hours with different concentrations of LPS (0,0.1,1,10,100 mg/L),and the expression levels of COX-2 were monitored with RT-PCR and dose-effect experiment was performed accordingly.Human BEAS-2B cells were treated with 10 mg/L LPS for 0,2,6,12 and 24 hours,and the expression levels of COX-2 were monitored with RT-PCR and dose-effect experiment was also performed.BEAS-2B cells were pretreated with 20 μmol/L SB203580 (p38 MAPK inhibitor) for 1 hour,and then exposed to 10 mg/L LPS for 2 hours.Effect of SB203580 on the expression of COX-2 was detected with RT-PCR.Results COX-2 expression tended to increase,when different concentrations of LPS treated BEAS-2B cells for 2 hours,with the expression level being obviously dose-dependent.After BEAS-2B cells were treated for 2 hours with 10 mg/L LPS,COX-2 expression reached peak,then decreased,and finally came to the basal level at 24 h.And no statistical significance could be noted,when it was compared with that of the control group (P ＜ O.05).p38 MAPK inhibitor,SB203580,could partially inhibit COX-2 expression induced by LPS in BEAS-2B cells.Conclusions LPS could induce the COX-2 expression in BEAS-2B cells in a dose-dependent manner,and the COX-2 expression reaches the peak at 2 h.p38 MAPK is involved in the COX-2 expression induced by LPS in BEAS-2B cells.

Objective To investigate the effect of lipopolysaccharide (LPS) on the expression of cycloxygenase-2 (COX-2) in human bronchial epithelial cells (BEAS-2B),and the role of p38 mitogen-activated protein kinase (MAPK) signal pathway in the expression of COX-2 induced by LPS.Methods Human BEAS2B cells were treated for 2 hours with different concentrations of LPS (0,0.1,1,10,100 mg/L),and the expression levels of COX-2 were monitored with RT-PCR and dose-effect experiment was performed accordingly.Human BEAS-2B cells were treated with 10 mg/L LPS for 0,2,6,12 and 24 hours,and the expression levels of COX-2 were monitored with RT-PCR and dose-effect experiment was also performed.BEAS-2B cells were pretreated with 20 μmol/L SB203580 (p38 MAPK inhibitor) for 1 hour,and then exposed to 10 mg/L LPS for 2 hours.Effect of SB203580 on the expression of COX-2 was detected with RT-PCR.Results COX-2 expression tended to increase,when different concentrations of LPS treated BEAS-2B cells for 2 hours,with the expression level being obviously dose-dependent.After BEAS-2B cells were treated for 2 hours with 10 mg/L LPS,COX-2 expression reached peak,then decreased,and finally came to the basal level at 24 h.And no statistical significance could be noted,when it was compared with that of the control group (P ＜ O.05).p38 MAPK inhibitor,SB203580,could partially inhibit COX-2 expression induced by LPS in BEAS-2B cells.Conclusions LPS could induce the COX-2 expression in BEAS-2B cells in a dose-dependent manner,and the COX-2 expression reaches the peak at 2 h.p38 MAPK is involved in the COX-2 expression induced by LPS in BEAS-2B cells.