BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

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 investigate the effects of precautionary high-flow oxygen therapy on preventing hypoxemia in patients with Stanford type A aortic dissection after intubation.Methods Totally 90 hospitalized patients with Stanford type A aortic dissection in our hospital were enrolled in this study.Forty-five patients were recruited in the control group from January to April 2017,and the common mask-type nebulizer was used for oxygen inhalation.From May to October in 2017,45 patients were recruited in the experimental group.The parameters of highflow oxygen therapy in the experimental group were set as oxygen concentration (FiO2) 40％～60％,oxygen flow rate 35～60 L/min.Then after 72h's therapy,normal mask oxygen therapy was provided as replacement therapy.Results Oxygenation index and oxygen partial pressure were increased in the experimental group than those in the control group,the rate of respiration and carbon dioxide partial pressure were decreased than those in the control group,and the differences were statistically significant(P＜0.05).The scores of oral nasal dryness symptom and sore throat symptom in the experimental group were lower than those in the control group in 24 h,48 h,72 h during therapy,and the differences were statistically significant (P＜0.05).The incidence of hypoxemia and the incidence of secondary intubation were lower in the experimental group than those in the control group(P＜0.05).Conclusion Precautionary high-flow oxygen therapy for patients with Stanford type A aortic dissection can increase PaO2/FiO2,PaO2,reduce PaCO2,respiratory rate,reduce respiratory symptoms,reduce the incidence of hypoxemia,and secondary intubation.

Objective To evaluate the influence of SOCS3 conditional ablation in macrophage polarization and functional recovery after spinal cord injury in mice.Methods The Socs3fVfl Nes cre mice were used to obtain nervous-system-restricted SOCS3 deletion models as experimental group (n=40),and littermate Socs3fl as control group (n=40).Mice (n=35) in each group were underwent T10 spinal cord compressing injury (the left 5 were as sham-operated controls);on the third,7th and 14th d of injury,injured tissues from 15 mice of each group were harvested;immunofluorescence was performed to detect the changes of M2a and M2c phenotypic marker Arginase1 and M1 and M2b phenotypic marker CD86;on the first,third,7th and 14th d of injury,injured tissues from the left 20 mice from each group were harvested;fluorescent quantitative real time-PCR was used to detect the macrophage phenotypic markers (Arginasel,CD206,iNOS and CD32),SOCS3 and STAT3 gene expressions;the above data from the sham-operated controls were used as base data.BMS scale was used to evaluate the motor functions of posterior limbs and bodies on the first,third,7th and 14th d of injury.Results The behavioral assessments of the experimental group were superior on the third,7th and 14th d of injury as compared with those of control group (P＜0.05).Immunofluorescence showed that as compared with the controls,the Socs3fVfl Nes cre mice had a predominance in distribution and population of Arginasel-positive macrophages in spinal cords on the third,7th and 14th d of injury;in contrast,the control group showed superiority of CD86 expression on the 7th and 14th d,with significant differences (P＜0.05).Similarly,fluorescent quantitative real time-PCR analysis demonstrated that gene expression of A rginase I on the 7th d of injury,that of CD206 on the 7th and 14th d of injury,and that of STAT3 on the third,7th,and 14th d of injury were significantly increased,whereas that of CD32 on the 14th d of injury and SOCS3 on the first and third d of injury were significantly reduced in the experimental group,as compared with those in the control group (P＜0.05).Conclusion SOCS3 conditional knockout can promote the formation of M2 macrophage,as well as good functional recovery after spinal cord injury in mice.

OBJECTIVETo study the effects of a Gold Belt (GB, a traditional Chinese herbal medicine) combined with methyl-prednisolone (MP) on the motor function and brain-derived neurotrophic factor (BDNF) expression in rats with contusive spinal cord injury (SCI).

METHODSThirty adult female SD rats were randomly divided into 5 equal groups, namely the sham-operated group, SCI group, SCI with MP treatment group (MP group, with intramuscular injection of 50 mg/kg MP within 8 hours after SCI and then dosage reduced 10 mg/kg daily), SCI with GB treatment group (GB group, with intragastric gavage of GB 50 mg/kg once daily for 7 days), and combined GB and MP treatment group. The Basso, Beattie and Bresnahan (BBB) locomotor scale was used to evaluate the hindlimb motor function of the rats on days 1, 3, 7, 14, 21 and 28 after the injury. After the last evaluation the rats were sacrificed for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of spinal cord.

RESULTSBDNF were distributed mainly in neurons in the spinal cord grey matter ventral horn and dorsal horn of the rats. The number of BDNF-positive neurons and BBB scores in the combined treatment group were significantly higher than those in the other 4 groups (P<0.05).

CONCLUSIONGB combined with MP produces better therapeutic effects for treating SCI than GB or MP used alone, and such effects are probably related with enhanced BDNF expression in the spinal cord.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Methylprednisolone ; pharmacology ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; metabolism

Objective To evaluate the alveolar bone thickness and root length changes of anterior teeth with cone-beam computed tomography(CBCT).Methods CBCT scans were taken for 12 skeletal Class Ⅲ patients who accepted the improved corticotomy(IC) procedures during pre-surgical orthodontics.The CBCT data in T1(the maxillary dental arch was aligned and leveled) and T2(extraction space closure) were superimposed and the alveolar bone thickness at root apex level and root length measurements were done.Results From T1 to T2,the buccal alveolar bone thickness for the upper lateral incisors increased from (1.89±0.83) to (2.47± 1.02) mm (P＜0.05),and for central incisors and for canines from (2.32±0.71) to (2.68 ± 1.48) mm and from (2.28 ± 1.08) to (2.41 ± 1.40) mm,respectively.According to Sharpe Grading System,the root resorption grade for 69 teeth of 72 was located in Grade 1,two teeth in Grade 2,one tooth in Grade 3.Conclusions The improved corticotomy had the potential to increase the buccal alveolar bone thickness and the root resorption in most teeth was in Grade 1 according to Sharpe grading system.

Objective To investigate the effect of the fibronectin extra domain A on the aggressiveness of salivary adenoid cystic carcinoma (SACC) cells,via the clustered regularly interspaced short palindromic repeats (CRISPR)/associated proteins (Cas) system.Methods One sgRNA was designed to target the upstream of the genome sequences of extra domain A(EDA) exon and the downstream.Then the sgRNA was linked into plasmid PX-330 and transfected into SACC-83 cells.PCR and DNA sequence were used to testify the knockout cells,and the monoclones of EDA absent SACC cells were selected (A+C-2,A+C-6,B+C-10).CCK-8 cell proliferation and invasion was then tested in control group and the experimental group.Results The sgRNA was successfully linked into PX-330 plasmid.Part of adenoid cystic carcinoma cells' SACC-83 genomic EDA exon was knocked out,and the knockdown efficiency was above 70％,but the total amount of fibmnectin did not change significantly.Three monoclones of EDA absent SACC-83 cells were successfully selected with diminished migration and proliferation.Conclusions The CRISPR/Cas9 system was a simplified system with relatively high knockout efficiency and EDA knockout could inhibiting SACC cell's mobility and invasiveness.

Objective To study the effects of a Gold Belt (GB, a traditional Chinese herbal medicine) combined with methyl-prednisolone (MP) on the motor function and brain-derived neurotrophic factor (BDNF) expression in rats with contusive spinal cord injury (SCI). Methods Thirty adult female SD rats were randomly divided into 5 equal groups, namely the sham-operated group, SCI group, SCI with MP treatment group (MP group, with intramuscular injection of 50 mg/kg MP within 8 hours after SCI and then dosage reduced 10 mg/kg daily), SCI with GB treatment group (GB group, with intragastric gavage of GB 50 mg/kg once daily for 7 days), and combined GB and MP treatment group. The Basso, Beattie & Bresnahan (BBB) locomotor scale was used to evaluate the hindlimb motor function of the rats on days 1, 3, 7, 14, 21 and 28 after the injury. After the last evaluation the rats were sacrificed for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of spinal cord. Results BDNF were distributed mainly in neurons in the spinal cord grey matter ventral horn and dorsal horn of the rats. The number of BDNF-positive neurons and BBB scores in the combined treatment group were significantly higher than those in the other 4 groups (P<0.05). Conclusion GB combined with MP produces better therapeutic effects for treating SCI than GB or MP used alone, and such effects are probably related with enhanced BDNF expression in the spinal cord.

Objective To study the effects of a Gold Belt (GB, a traditional Chinese herbal medicine) combined with methyl-prednisolone (MP) on the motor function and brain-derived neurotrophic factor (BDNF) expression in rats with contusive spinal cord injury (SCI). Methods Thirty adult female SD rats were randomly divided into 5 equal groups, namely the sham-operated group, SCI group, SCI with MP treatment group (MP group, with intramuscular injection of 50 mg/kg MP within 8 hours after SCI and then dosage reduced 10 mg/kg daily), SCI with GB treatment group (GB group, with intragastric gavage of GB 50 mg/kg once daily for 7 days), and combined GB and MP treatment group. The Basso, Beattie & Bresnahan (BBB) locomotor scale was used to evaluate the hindlimb motor function of the rats on days 1, 3, 7, 14, 21 and 28 after the injury. After the last evaluation the rats were sacrificed for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of spinal cord. Results BDNF were distributed mainly in neurons in the spinal cord grey matter ventral horn and dorsal horn of the rats. The number of BDNF-positive neurons and BBB scores in the combined treatment group were significantly higher than those in the other 4 groups (P<0.05). Conclusion GB combined with MP produces better therapeutic effects for treating SCI than GB or MP used alone, and such effects are probably related with enhanced BDNF expression in the spinal cord.

Objective: To observe the clinical effect in the treatment of toothache by puncturing Hegu(LI 4). Methods: Two hundred and seventy-eight cases of the patients were randomly divided into the treatment group (139 cases) and the control group (139 cases). The treatment group was treated by puncturing Hegu (LI 4) with electric stimulation and the control group, by puncturing Chenshan (BL 57) with electric stimulation, for 3 days as one course of the treatment,to grade pain and observe the anesthetic effect respectively. Results: There was no significant difference in the remarkable effective rate between the two groups before withdrawal of the needle in the treatment for one day (P＞0.05). In the other times, the remarkable effective rate was obviously higher in the treatment group than in the control group (P＜0.05). Conclusion:Acupuncture on Hegu (LI 4) is effective in treating toothache.