An elderly female melanoma patient who experienced severe liver injury after treatment with pembrolizumab and axitinib,which improved with glucocorticoid therapy.Through medication analysis and adverse reaction scale evaluated,it was considered that severe liver injury was more closely related to the immune checkpoint inhibitor,pembrolizumab.After a comprehensive analysis of the relationship between liver injury and immunotherapy,as well as the benefits and risks of immunotherapy for patients,immunotherapy was rechallenged 40 days after discontinuation of pembrolizumab.Restarting treatment with pembrolizumab after immune-mediated hepatitis poses a risk of recurrence of hepatotoxicity.After reviewing related literature,it had been found that the incidence of severe hepatotoxicity caused by rechallenging treatment was low,and the overall safety was controllable.Pembrolizumab had brought therapeutic benefits to patients,with no further immune-mediated liver injury of 5 cycles medication.This case can provide a reference for rechallenging immunotherapy after immune-mediated hepatitis.

Objective:To evaluate the relationship between the mechanism of preoperative sleep deprivation aggravating postoperative cognitive dysfunction and theta oscillations in the hippocampal CA1 region in aged mice.Methods:Twenty-four SPF male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 3 groups ( n=8 each) by a random number table method: normal control group (group C), operation group (group S) and preoperative sleep deprivation + operation group (group SD+ S). The sleep deprivation model was established using the sleep deprivation rod method, and the sleep deprivation time was 24 h before operation. The sleep deprivation rod was set to rotate continuously at 6 rpm/min, and the direction was randomly reversed to force the mice to exercise to achieve the purpose of sleep deprivation. Group C received no treatment. Group S underwent exploratory laparotomy under isoflurane anesthesia. After sleep deprivation for 24 h, SD+ S group underwent exploratory laparotomy under isoflurane anesthesia. Y-maze and Morris water maze tests were used to evaluate postoperative cognitive function. The theta oscillations in the hippocampal CA1 region were observed and recorded by EEG electrodes in vivo. The animals were then sacrificed and brain tissues were obtained for determination of the density of dendritic spines in the hippocampal CA1 region. Results:Compared with group C, the number of crossing the original platform was significantly decreased, and the time of staying at the original platform quadrant and time of exploring the novel arm were shortened, and the number of entries into the novel arm was reduced, the density of dendritic spines in the hippocampal CA1 region was reduced, and the percentage of theta oscillation power was decreased during the Y maze test in group S ( P<0.05). Compared with S group, the number of crossing the original platform was significantly decreased, and the time of staying at the original platform quadrant and time of exploring the novel arm were shortened, and the number of entries into the novel arm was reduced, the density of dendritic spines in the hippocampal CA1 region was reduced, and the percentage of theta oscillation power was decreased during the Y maze test in SD+ S group ( P<0.01). Conclusions:The mechanisms by which preoperative sleep deprivation exacerbates postoperative cognitive dysfunction may be related to reduction in theta oscillations in the hippocampal CA1 region of aged mice.

Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

As a novel mode of cell death, pyroptosis plays an important role in nonalcoholic fatty liver disease (NAFLD), and the research on pyroptosis may help to explore new therapeutic targets for NAFLD. This article reviews the advances in pyroptosis from the research background and mechanism of pyroptosis and the role of pyroptosis in NAFLD and elaborates on the pyroptosis execution molecules such as GSDME and caspase-11 and the function of inflammasomes including AIM2.

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

Lung transplantation is an effective treatment for end-stage lung diseases in children, and the only treatment for children with no response to conservative treatment.However, merely a few transplantation centers at home and abroad can provide lung transplantation at present.The mortality of pediatric lung transplantation is high, and it is difficult for donor matching.Besides, it has many complications.In recent years, pediatric lung transplantation has made positive progress and technological breakthroughs in many aspects.In this article, research progress in pediatric lung transplantation at home and abroad was reviewed.

Objective:To investigate the effect of different strategies on auricle reconstruction in microtia with very low hairline according to the skin condition of retroauricular mastoid region and the degree of temporal bone development.Methods:The clinical data of patients with very low hairline congenital microtia admitted to the Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2014 to June 2019 were retrospectively analyzed. Surgical plan: the patients with moderate temporal bone development and thin and poor elasticity skin were treated with retroauricular skin expansion combined with laser hair removal; the patients with moderate temporal bone development and thick and loose skin were treated with fasciocutaneous flap expansion combined with laser hair removal; the patients with poor temporal bone development were treated with temporal superficial fascia combined with Medpor frame for one-time reconstruction. All patients were followed up to investigate their satisfaction with the three-dimensional structure and subunit morphology of the reconstructed ear, and the complications were recorded.Results:A total of 68 patients, 55 males and 13 females, aged from 5 to 22 years old, with an average of 10.4 years old, were included in this study. Among them, 22 patients were treated with retroauricular skin expansion combined with laser hair removal, 41 patients were treated with retroauricular fasciocutaneous flap expansion combined with laser hair removal, and 5 patients were treated with temporoparietal superficial fascia combined with Medpor frame for one-stage reconstruction. The follow-up ranged from 10 to 24 months (average 13 months). The three-dimensional structure and local subunits of 66 cases of reconstructed ears were in good shape, and the operation area recovered well without obvious scar hyperplasia and chest deformity. Among them, 6 patients remained a small amount of hair after laser hair removal treatment, and the satisfactory effect was achieved after re-hair removal treatment. The satisfaction rate of patients was 97.1% (66/68). Two cases of auricle reconstruction by retroauricular skin expansion combined with laser hair removal showed cartilage exposure after operation, and recovered with temporoparietal fascial flap after. No subcutaneous hematoma, poor skin graft survival, cartilage absorption, deformation and other complications occurred in all cases.Conclusions:According to the skin condition and temporal bone development degree of patients with very low hairline, different treatment schemes can obtain better auricle shape, improve postoperative patient satisfaction and reduce complications.

Objective:To investigate the clinical effect of two-stage auricular reconstruction combined with Bonebridge implantation in the treatment of congenital microtia.Methods:The clinical data of 52 patients with congenital microtia and hearing impairment were retrospectively analyzed. The patients were admitted to the Plastic Surgery Hospital of Chinese Academy of Medical Sciences and Beijing Tongren Hospital Affiliated to Capital Medical University from June 2017 to August 2019. There were 35 males and 17 females, aged 6-12 years. All patients received the two-stage surgery. The first stage surgery was Nagata’s technique described as follows: rib cartilage harvest and framework implantation. The second stage surgery combined auricle elevation with Bonebridge implantation. Postoperative follow-up was conducted to evaluate the effect of the operation through auricular morphology and auditory evaluation. The auricular morphology was subjectively evaluated by the patient and the patient’s family members. The audiometric evaluation mainly included the comparisons of the pure tone audiometry results and speech recognition rate of the patients before and after the operation. SPSS 19.0 software was used for data analysis. The measurement data were showed as Mean±SD, and the comparison results were analyzed by paired t test. P<0.05 was considered statistically significant. Results:After follow-ups of 3-10 months, with an average of 6 months, the spatial three-dimensional structure and local subunit morphology of the reconstructed ears were satisfactory in 47 patients (90.4%). Four patients had obvious scarring or keloid in retroauricular region, which affected the aesthetic outcome. The results of pure tone audiometry at 3 weeks after surgery showed that the postoperative air conduction threshold was (38.8±7.2) dB HL, which decreased by (33.6±6.2) dB HL compared to that before surgery (72.4±9.0) dB HL, and the difference was statistically significant ( t=38.13, P<0.001). The speech recognition rate was increased by 24%-67%, which was improved from 31.9% before surgery to 85.0% after surgery. The difference was statistically significant ( t=-40.15, P<0.001). Conclusions:Auricular reconstruction and Bonebridge implantation were carried out in one stage of surgery, so that the patients with congenital microtia could obtain good auricular morphology and improve their hearing significantly.

Objective:To investigate the clinical effect of two-stage auricular reconstruction combined with Bonebridge implantation in the treatment of congenital microtia.Methods:The clinical data of 52 patients with congenital microtia and hearing impairment were retrospectively analyzed. The patients were admitted to the Plastic Surgery Hospital of Chinese Academy of Medical Sciences and Beijing Tongren Hospital Affiliated to Capital Medical University from June 2017 to August 2019. There were 35 males and 17 females, aged 6-12 years. All patients received the two-stage surgery. The first stage surgery was Nagata’s technique described as follows: rib cartilage harvest and framework implantation. The second stage surgery combined auricle elevation with Bonebridge implantation. Postoperative follow-up was conducted to evaluate the effect of the operation through auricular morphology and auditory evaluation. The auricular morphology was subjectively evaluated by the patient and the patient’s family members. The audiometric evaluation mainly included the comparisons of the pure tone audiometry results and speech recognition rate of the patients before and after the operation. SPSS 19.0 software was used for data analysis. The measurement data were showed as Mean±SD, and the comparison results were analyzed by paired t test. P<0.05 was considered statistically significant. Results:After follow-ups of 3-10 months, with an average of 6 months, the spatial three-dimensional structure and local subunit morphology of the reconstructed ears were satisfactory in 47 patients (90.4%). Four patients had obvious scarring or keloid in retroauricular region, which affected the aesthetic outcome. The results of pure tone audiometry at 3 weeks after surgery showed that the postoperative air conduction threshold was (38.8±7.2) dB HL, which decreased by (33.6±6.2) dB HL compared to that before surgery (72.4±9.0) dB HL, and the difference was statistically significant ( t=38.13, P<0.001). The speech recognition rate was increased by 24%-67%, which was improved from 31.9% before surgery to 85.0% after surgery. The difference was statistically significant ( t=-40.15, P<0.001). Conclusions:Auricular reconstruction and Bonebridge implantation were carried out in one stage of surgery, so that the patients with congenital microtia could obtain good auricular morphology and improve their hearing significantly.

Objective:To explore the epidemiologic characteristics and the possible risk factors of microtia in China. Meanwhile, the significant variables related to severe cases are integrated into a predictive nomogram.Methods:A total of 593 patients with congenital microtia from July 2015 to July 2018 were included. Patients conforming to congenital microtia with or without associated malformations were enrolled in this study, and patients with clear chromosomal syndromes were excluded. Questionnaire surveys were conducted among the parents to collect the demographic information and risk factors for exposure during perinatal period. Using Chi-Square and Fisher’s tests to statistically analyze the frequencies of variables. Univariate and multivariate logistic regression analysis were used to select variables related to severe cases for constructing nomogram. Concordance index (C-index), calibration plot, Hosmer-Lemeshow test, and receiver operating characteristics (ROC) curve were used to assess the nomogram model.Results:Of the patients, 456 (76.9%) were male and 137 (23.1%) were female. Right side was involved in 329 cases (55.5%), left side in 217 cases (36.6%) and both sides in 47 cases (7.9%). Among them, 16 cases were familial and the rest were sporadic. Multiple deformations were in 392 cases (66.1%). Maternal illness in early pregnancy( OR=2.205, 95% CI: 1.020-4.020)and parternal drinking history( OR=2.221, 95% CI: 1.329-3.677)were independent risk factors for severe microtia. While mother aged from 26 to 35 years old ( OR=0.507, 95% CI: 0.281-0.913; OR=0.258, 95% CI: 0.125-0.531) and father living in plain area( OR=0.512, 95% CI: 0.288-0.913)may be protective factors. All the significant predictors were combined into a predictive nomogram. The C-index was 0.703(95% CI: 0.646-0.760). The calibration plotshowed good performance of the nomogram, and the model passed Hosmer-Lemeshow goodness-of-fit test ( χ2=4.512, P=0.808). ROC curve analysis revealed a high sensitivity and specificity. Conclusions:The majority of microtia patients are male, sporadic, occur on right side, and often associated with other malformations. This nomogram predicting severe microtia based on multiple parental risk factors was with good discrimination and accuracy, which could provide scientific guidance for individualized prevention in clinical practice.