OBJECTIVE To investigate the efficacy and safety of aerosol inhalation of polycolistin B in the treatment of severe pneumonia combined with mechanical ventilation， and to provide a reference of real-world data for clinical drug therapy. METHODS A retrospective cohort study was conducted to analyze the clinical data of 87 patients with severe pneumonia combined with mechanical ventilation at the First Affiliated Hospital of Shandong First Medical University from January 2021 to February 2023. According to route of administration， all patients were divided into combined group （24 cases， receiving aerosol YXH2021ZX013） inhibition of polycolistin B combined with intravenous dripping） and routine group （63 cases， intravenous dripping of polycolistin B alone）. The differences in efficacy （mortality，clinical response rate and bacterial clearance rate）and safety （elevated serum creatinine， bronchospasm and skin pigmentation） were compared between two groups； the influential factors of primary outcome index as mortality were analyzed through univariate analysis and multivariate Logistic regression analysis. RESULTS In terms of efficacy， there were no statistical differences in mortality（37.50% vs. 41.27%， P＝0.749）， clinical response rate （54.17% vs. 55.56%， P＝0.907） and bacterial clearance rate （45.83% vs. 44.44%， P＝0.907） between the two groups. In terms of safety， the incidence of bronchospasm in the combined group was significantly higher than that of the routine group （12.50% vs. 0， P＝0.028）， but the differences in incidence of elevated serum creatinine and skin pigmentation between two groups were not statistically significant （P＞0.05）. Univariate analysis showed that the moralities were higher in the case of infected with Acinetobacter baumannii， Klebsiella pneumoniae and combined use of quinolones （P＜0.05）； multivariate Logistic regression analysis showed that infection with A. baumannii （OR＝3.36， P＝0.014） and combined use of quinolones （OR＝3.54， P＝0.013） were independently associated with mortality （P＜0.05）. CONCLUSIONS For severe pneumonia patients with mechanical ventilation， intravenous dripping of polycolistin B combined with aerosol inhalation does not show superior efficacy compared with intravenous dipping of polycolistin B alone， but significantly increases the incidence of bronchospasm. Infection with A. baumannii and combined use of quinolones are independent risk factors for the increase of mortality.

Objective To analyze the risk factors and clinical prognosis of acute kidney injury (AKI) early after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation or combined heart-lung transplantation were retrospectively analyzed, and they were divided into the AKI group (n=104) and non-AKI group (n=51) according to the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of AKI early after lung transplantation was summarized. The main indexes of recipients were collected. The risk factors of the occurrence of AKI early after lung transplantation were subjected to univariate and multivariate analysis. The clinical prognosis of lung transplant recipients was evaluated and the survival curve was delineated. Results The incidence of AKI early after lung transplantation was 67.1%(104/155), including 47 recipients with stage 1 AKI, 34 recipients with stage2 AKI and 23 recipients with stage 3 AKI, respectively. Sixteen recipients required continuous renal replacement therapy (CRRT) early after lung transplantation. Preoperative complication with diabetes mellitus, preoperative complication with pulmonary hypertension, intraoperative mean arterial pressure (MAP) < 60 mmHg, intraoperative massive blood transfusion, and treatment with excessive therapeutic concentration of tacrolimus (Tac) within postoperative 1 week were the independent risk factors for the occurrence of AKI early after lung transplantation. Up to the end of follow-up, 66 recipients (42.6%) died, including 50 recipients in the AKI group and 16 recipients in the non-AKI group. The cumulative survival rate in the AKI group was significantly lower than that in the non-AKI group (40% vs. 66%, P < 0.05). With the increase of AKI severity, the cumulative survival rate of lung transplant recipients was decreased. Conclusions AKI develops early after lung transplantation with high incidence and poor clinical prognosis. Preoperative complication with diabetes mellitus and pulmonary hypertension, intraoperative MAP < 60 mmHg and massive blood transfusion, and treatment with excessive therapeutic concentration of Tac within postoperative 1 week are the independent risk factors for the occurrence of AKI early after lung transplantation.

Acute cellular rejection (ACR) is a common complication after lung transplantation, which is mainly caused by the immune response of T lymphocytes recognizing the major histocompatibility complex on the cellular surface of grafts. It is currently considered as the main pattern of acute rejection. ACR is not only a direct cause of death of recipients, but also a high-risk factor for chronic rejection after lung transplantation. Nevertheless, it is a challenging task to deliver the diagnosis and treatment of ACR following lung transplantation. In this article, new progresses on the risk factors, pathogenesis, diagnosis and treatment of ACR in lung transplant recipients were summarized, aiming to improve the diagnostic and treatment efficiency of ACR and prolong the survival of recipients.

Objective To analyze the dynamic changes and the influencing factors of T lymphocyte subsets in recipients with stable graft status within 1 year after lung transplantation. Methods Clinical data of 41 recipients with stable graft status after allogeneic lung transplantation were analyzed. The absolute value and ratio of T lymphocyte subsets in peripheral blood from recipients were measured by flow cytometry before operation, 2 weeks and each month (within 1 year) after operation, respectively. The effects of age, gender, body mass index (BMI), surgical method, incidence of primary graft dysfunction (PGD) after operation, and primary disease upon the absolute values of T lymphocytes were evaluated. Results Within 1 year after lung transplantation, the absolute values of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes and CD4⁺/CD8⁺ ratio were changed over time (all P < 0.001). Compared with preoperative values, there was no statistical significance in the absolute values of CD3⁺ and CD3⁺CD4⁺T lymphocytes at 12 months after operation (P=0.659, 0.109), whereas the absolute value of CD3⁺CD8⁺T lymphocytes was increased (P=0.02) and the CD4⁺/CD8⁺ ratio was decreased (P < 0.001). Age, gender, BMI, surgical method and incidence of PGD after operation exerted no significant effect on the dynamic changes of absolute values of CD3⁺CD4⁺ and CD3⁺CD8⁺T lymphocytes (all P > 0.05). Primary disease before lung transplantation exerted no effect on the changes of CD3⁺CD4⁺T lymphocytes, whereas the postoperative absolute value of CD3⁺CD8⁺T lymphocytes was higher in recipients with infectious lung diseases (P < 0.05). Conclusions The absolute values of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes in recipients with stable graft status after lung transplantation are relatively low in the early stage after lung transplantation, then gradually restore, and stabilize at 6 months after operation. Dynamic changes are not associated with age, gender, BMI, surgical method and incidence of PGD after operation of recipients.

Objective:To explore the clinical manifestations and imaging features of nocardia infection (NI) after lung transplantation and boost the diagnosis and treatment of NI.Methods:From January 2018 to December 2019, basic profiles, clinical manifestations, laboratory examinations, imaging features and treatment outcomes of 5 lung transplant recipients with a diagnosis of NF were retrospectively analyzed and summarized with the relevant literatures. There were 4 males and 1 female with a median age of 66(26-69) years. 3 patients were single-lung transplantation, 2 patients were bilateral-lung transplantation. The median time from an initial diagnosis of NI to lung transplant surgery was 6(5-19) months. Common symptoms included fever, cough with yellow phlegm and shortness of breath. Laboratory findings showed lymphopenia, significantly high C-reactive protein levels, a slight elevation of procalcitonin, hypoproteinemia and anemia. The major manifestations of high-resolution computed tomography (CT) included multiple nodules, consolidation, cavitation and pleural effusion.Results:Five strains of N. farcinica were identified from bloodstream infection ( n=2) and pulmonary infection ( n=3). After with a combined therapy of two sensitive agents, all patients improved and were discharged from hospital. During follow-ups, one patient died and the remainders were cured. Conclusions:Nocardia infection occurs in lung transplant recipients mostly within 1 year post-operation. There are non-specific symptoms and imaging features of multiple nodules and consolidation. Combination therapy of sensitive agents is indicated for lung transplant recipients with NI.

Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.

Objective:To study the effects of hypertensive disorders of pregnancy (HDP) on the birth weight (BW) differences in twins.Method:From January 2011 to January 2020, twins delivered in our hospital were retrospectively analyzed. The twins born to HDP mothers were the HDP group and those born to healthy mothers were the control group. The maternal and neonatal data of the two groups were collected and the effects of HDP on the BW differences were analyzed.Result:The age of the mothers, the proportion of mothers of older ages and more-than-once delivery in HDP group (418 cases) were significantly higher than the control group (499 cases) [(31.4±5.3) years vs. (30.4±3.8) years, 26.6% (111/418) vs. 12.6% (63/499), 20.6% (86/418) vs. (15.0% (75/499)] ( P<0.05). The gestational age (GA) of newborns in the HDP group (836 cases) was significantly lower than the control group (998 cases) [(35.1±2.2) weeks vs. (36.7±1.2)]( P<0.05). The proportion of twins with GA <34 weeks in the HDP groups was significantly higher than the control group [24.2% (101/418) vs. 3.8% (19/499)] ( P<0.05). Cesarean section was the main delivery mode in both groups. The BW differences of the twins in the HDP group were larger than the control group [22.4% (9.1%, 31.9%) vs. 13.1% (5.8%, 19.6%)]. Significantly more twins in the HDP group showed ≥30% BW difference than the control group [28.7% (120/418) vs. 3.8% (19/499)] ( P<0.05). The incidences of BW discordant in twins (BWDT) in the HDP group was significantly higher than the control group [BWDT≥15%:61.5% (257/418) vs. 38.3% (191/499), BWDT≥20%: 51.4% (215/418) vs. 25.3% (126/499)] ( P<0.05).Among twins with GA of 34~37 weeks, the BW of the bigger infants and the smaller infants in the HDP group were all lower than the control group and the percentage of BW difference was significantly higher than the control group ( P<0.05). Conclusion:HDP may influence the intrauterine growth of the twins, aggravate the BW differences and increase the incidences of BWDT. It is necessary to make better prenatal management of HDP and closely monitor the intrauterine growth of the fetuses.

Growth plate,the developmental center of endochondral osteogenesis,can be divided morphologically and functionally into a resting zone,a proliferative zone,a prehypertrophic zone and a hypertrophic zone.Injuries to growth plate often lead to bone growth defects including limb length discrepancy and angulation deformity in children.Currently,their orthopedic corrective surgeries are invasive and limitedly effective and no effective biotherapy has been available.Previous studies on animal models of growth plate damage have investigated the related cellular and molecular events in the repair of damaged growth plates in the 4 distinct inflammatory,fibrogenic,osteogenic and remodeling phases.Related molecules involved in the regulation of the above processes,such as inflammatory cytokines tumor necrosis factor alpha,mitogenic platelet-derived growth factor and bone morphogenetic protein,are found to participate in the regulation of growth plate injury.Exploration of the mechanisms may provide new targets for biotherapy.In addition,development of cartilage tissue engineering,especially application of mesenchymal stem cells,also provides potential interventions for growth plate injury.

Objective:To explore the significance of US lung allocation score (LAS) in Chinese lung transplant recipients.Methods:The clinical data were analyzed for 173 lung recipients from May 2005 to March 2018. The LAS of each patient was calculated by an online LAS calculator of Organ Procurement and Transplantation Network (OPTN).Results:The mean age was (56.49±12.64) years and the mean LAS (56.63±18.39)(32.79-90.70). The underlying diseases were chronic obstructive pulmonary disease (COPD, n=62), interstitial lung disease (n=85), bronchiectasis (n=11), pulmonary arterial hypertension (n=8) and others (n=7). And the value of LAS was (47.85±15.22) vs. (61.89±18.63) vs. (56.58±18.91) vs. (55.23±10.74) vs. (72.45±16.41). LAS of COPD patients was significantly lower than that of interstitial lung disease ( P<0.001). Mean LAS was the highest in endotracheal intubation or ECMO group (79.15±7.95), then non-invasive ventilation group (48.42±11.58) and lowest in oxygen inhalation group (44.11±8.81)( P<0.001). Recipients were divided into three groups of LAS <50 for low-risk, 50-75 for moderate-risk and >75 for high-risk. Survivals at 90 days and 1 year were 90.5% vs. 81.8% vs. 71.1% and 85.4% vs. 74.4% vs. 57.8% ( P=0.002). Conclusions:LAS can not only reflect the urgency of recipients waiting for lung transplantation but also predict postoperative period. LAS score should be employed for selecting suitable lung transplant recipients in China and the optimal LAS lies between 30 and 75.

Objective:To explore the diagnosis and treatment strategies of primary ciliary dyskinesia (PCD).Methods:A 37-year-old male recipient who had repeated cough and sputum from childhood, with shortness of breath after activity and progressive development, the number of hospitalizations per year was ≥6 times, the MRC score was 2~3 diagnosed with primary ciliary dyskinesia through medical examination and multidisciplinary consultation, and received allogeneic double lung transplantation after medical treatment failure. Search related domestic and foreign literatures to explore and analyze the etiology, pathogenesis, clinical manifestations and imaging features, diagnosis and treatment of PCD.Results:PCD is an autosomal hereditary disease. Due to abnormal skeletal structure and/or functional development, clinical manifestations are mostly chronic sinusitis, bronchiectasis, otitis media and infertility. Chest imaging showed situs inversus totalis, right heart and diffuse cystic bronchiectasis infection with bronchial wall thickening, diagnosis depends on clinical manifestations, saccharin test, nasal nitric oxide test, high-speed video microscopy analysis, transmission electron microscopy, genetic testing and immunofluorescence.Conclusions:Lung transplantation is the only effective treatment for end-stage PCD. It not only saves patients' lives, but also significantly improves their quality of life.