Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Objective To study the expression of lipoic acid synthase(LIAS)in the liver and kidney of Leprdb/db mice with deficient leptin receptor. Methods Eight 10-week old male Leprdb/ +mice and Leprdb/dbmice were included in this study. The body weight of rats in the two groups was measured. Fasting blood glucose(FPG)was measured with blood glucose test strips for all mice after fasting for 8 hours. Blood samples were obtained from the abdominal aorta and the animals were sacrificed. The liver and kidney were weighed. The right lobe of liver and the left kidney samples were fixed in 4% paraformaldehyde for pathological examination. Serum samples were separated and the sereum contents of CHO, TG,HDL and LDL were detected. The mitochondria of liver and kidney tissues were extracted with a mitochondrial isolation kit, and the protein was extracted. The expression of LIAS protein was detected by western blot. Results Histopathological observation showed that the liver and kidney tissues of Leprdb/ +mice have intact and clear structure. But the liver tissue of Leprdb/dbmice showed fatty degeneration, the kidney tissue showed glomerular hypertrophy, basement membrane thickening, mesangial area widened, including mesangial cells and mesangial matrix increased. The GLU,CHO,TG,LDL and AST of Leprdb/dbmice were significantly increased compared with those of Leprdb/ +mice(P<0.05). Compared with Leprdb/ +mice,the LIAS protein expression was significantly increased in the liver and kidney mitochondria of Leprdb/dbmice(P<0.05). Conclusions There is impaired glucose and lipid metabolism in the Leprdb/dbmice which has defect leptin receptor,and the expression of LIAS protein in liver and kidney of the Leprdb/dbmice is higher than that of Leprdb/ +mice.

Objective To establish an efficient method of genotyping for Leprdb/ +mouse offsprings by TaqMan probe quantitative fluorescence PCR. Methods Genome DNA was extracted from tails of 228 Leprdb/ +mouse offsprings. PCR primers and TaqMan probes were designed according to the mutation sites of Lepr gene(rs1801133). Real time PCR assay was applied and SNP loci were typed with SDS software. The genotyping of 2-month old Leprdb/dbmice was validated by the phenotype and Hardy-Weinberg equilibrium test was performed. Results 228 samples were detected by the established TaqMan fluorescence quantitative PCR assay. 64 mice were of GG genotype, with a genotype frequency of 0.1929. 123 mice were of GT genotype, with a genotype frequency of 0.5395. 41 mice were of TT genotype, with a genotype frequency of 0.2807. Compared with the phenotype typing,the sensitivity of the TaqMan fluorescence quantitative PCR was 97.56% and the specificity was 99.47%. Conclusions TaqMan probe quantitative fluorescence PCR assay is a simple and efficient method,and can be used to detect the genotype of Leprdb/ +mouse offsprings.

Objective To observe the feasibility of posterior internal fixation with pedicle screw rod system for upper cervical vertebra injury. Methods 16 patients with upper cervical vertebra injury accepted posterior pedicle screw system internal fixation were reviewed. Results Venous plexus behind C2 damaged in operation in a case, who needed a microscope for hemostasis. No complication, such as neurological symptoms worse, cerebrospinal fluid leakage, hematoma and infection of incision happened post operation. The neurological symptoms improved 81.8% in all the 7 cases who complained before operation. No complication was found in the follow-up 3 to 18 months after discharge. Their activities of upper cervical was basically unaffected. Conclusion Posterior internal fixation with pedicle screw rod system can provide stable support for patients with upper cervical injury.