Objective:To explore the trends and outcomes for heart transplantation (HT) in elderly recipients and further examine the related risk factors.Methods:Between June 2004 and December 2021, retrospective review was conducted for the relevant clinical data and age distribution of 1044 HT recipients aged ≥18 year at Fuwai Hospital. The study population was assigned into two groups of elder (≥60 year, n=877) and non-elder (<60 year, n=157). Subgroup analysis was made between recipients aged <65 year (n=107) and those aged ≥ 65 year (n=50) in elder group. Baseline demographic profiles, clinical data, in-hospital and one-year post-transplant mortality and long-term survival were compared between two groups. Then a further comparison of long-term survival was conducted among the groups of non-elder, elder aged <65 year and elder aged ≥65 year. Cox proportional risk regression and multivariate Logistic regression models were utilized for examining the relevant risk factors for cumulative survival rate and short-term mortality. Kaplan-Meier analysis was employed for plotting survival curves and Log-rank test for comparison. Multivariate Cox proportional risk regression model was utilized for examining the relevant risk factors for cumulative survival rate and multivariate Logistic regression model for analyzing the relevant risk factors for short-term mortality. After adjusting for other confounding factors, the impact of recipient age on survival post-HT was determined.Results:The number of elderly HT recipients spiked annually at our center while average age of adult recipients and average age of elderly recipients have remained relatively constant. The median follow-up period was 6.5 years. Regarding baseline data, statistically significant differences existed in ratio of males [84.7%(113/157) vs 77.5%(687/877)], hypertension history [20.4%(32/157) vs 8.9%(79/877)], smoking history [47.1%(74/157) vs 36.1%(320/877)], diabetic history [33.8%(53/157) vs 14.7%(130/877)], preoperative ICD/CRT/CRT-D implantation [28.0%(44/157) vs 18.0%(160/877)], value of creatinine [(105.3±25.3) vs (96.8±35.0) μmol/L], IMPACT score [(6.9±2.4) vs (4.2±2.9) point], serum total bilirubin [19.7(13.6, 30.3) vs 23.7(15.8, 36.8) μmol/L], mean pulmonary arterial pressure [(26.0±10.3) vs (29.7±11.0) mmHg (1 mmHg=0.133 kPa)] and ischemic duration [(274.7±105.6) vs (296.0±120.4) min] (all P<0.05). No significant inter-group difference existed in in-hospital mortality [4.5%(7/157) vs 4.7%(42/887)] or 1-year mortality [5.7%(9/157) vs 6.5%(58/887)] ( P=0.88, P=0.70); in-hospital mortality and 1-year postoperative mortality of recipients aged ≥65 years 10.0%(5/50) and 14.0%(7/50) were both higher than those aged <65 year [1.9%(2/107), 1.9%(2/107)]. The differences were both statistically significant ( P=0.02, P<0.01). Kaplan-Meier survival analysis indicated that long-term survival rate was lower in elder group than that in non-elder group and the difference was statistically significant ( P=0.046). Long-term survival rate of elders aged ≥65 year was lower than that of non-elders aged <65 year and the difference was statistically significant ( P<0.01). Regression analysis indicated that age of recipient ≥65 year, preoperative creatinine ≥133 μmol/L, preoperative total bilirubin ≥25.65 μmol/L and preoperative support of extracorporeal membrane oxygenation (ECMO) were independent risk factors for short/long-term mortality post-HT. Conclusion:Although long-term prognosis of elderly recipients is slightly worse than that of non-elderly ones, in-hospital mortality and one-year postoperative mortality are similar between two groups. For elderly recipients with fewer comorbidities and better preoperative status, they should not be excluded from HT based solely upon age. The long-term prognosis of recipients aged ≥65 year remains poor and HT decisions should be made carefully.

Objective To investigate the improvement of oxygenation after the treatment of prone position in patients with severe acute respiratory distress syndrome (ARDS) caused by pneumocystis jirovecii pneumonia (PJP) after kidney transplantation. Methods Clinical data of 5 cases of moderate and severe ARDS caused by PJP after kidney transplantation were analyzed retrospectively, and clinical characteristics, treatment regimen and prognosis were summarized. Results Clinical manifestations of 5 patients were fever, dry cough, chest tightness, shortness ofbreath,sweating and fatigue, and body temperature fluctuated between 38 ℃ and 39 ℃, percutaneous arterial oxygen saturation(SpO₂) was gradually decreased, and respiratory distress symptoms were worsened. Pulmonary CT scan showed diffuse ground-glass shadow. After transfer to intensive care unit (ICU), immunosuppressive drugs were terminated, and all patients were given with compound sulfamethoxazole, caspofungin, low-dose glucocorticoids against pneumocystis jirovecii (PJ), oxygen therapy and other symptomatic supportive treatments. Four patients diagnosed with severe ARDS upon admission to ICU were treated in a prone position. One patient with moderate ARDS was not kept in a prone position. At 1 d after treatment in a prone position, partial pressure of arterial oxygen (PaO₂) and oxygenation index were increased, whereas alveolar-arterial oxygen difference (A-aDO₂) was decreased compared with before treatment (allP<0.05). Compared with 1 d after treatment, SpO₂, PaO₂ and oxygenation index were all increased, while A-aDO₂ was decreased at 4 d after treatment (all P<0.05). Box diagram showed that oxygenation index showed an overall upward trend after prone-position treatment, whereas A-aDO₂ showed an overall downward trend. The length of ICU stay of 5 patients was 14 (8, 29) d. All patients in a prone position did not develop complications, such as skin pressure sore, tube detachment and tube displacement, etc. Among 5 patients, 4 patients were mitigated, and 1 patient died of septic shock and multiple organ failure. Conclusions For both conscious and intubated patients, a prone position may significantly improve oxygenation and prognosis of patients with severe ARDS caused by PJP after kidney transplantation. Early diagnosis and accurate and standardized treatment play a pivotal role in enhancing cure rate.

Objective To summarize the incidence of cardiac allograft vasculopathy (CAV) after heart transplantation and the effect on the long-term survival of recipients. Methods Clinical data of 1 006 heart transplant recipients were retrospectively analyzed. Of 48 CAV patients, 4 cases were not included in this analysis due to lack of imaging evidence. A total of 1 002 recipients were divided into the CAV group (n=44) and non-CAV group (n=958) according to the incidence of CAV. The incidence of CAV was summarized. Clinical data of all patients were statistically compared between two groups. Imaging diagnosis, coronary artery disease, drug treatment and complications, postoperative survival and causes of death of CAV patients were analyzed. Results Among 1 006 heart transplant recipients, 48 cases (4.77%) developed CAV. Compared with the non-CAV group, the proportion of preoperative smoking history, preoperative hypertension history, coronary artery disease and perioperative infection was significantly higher in the CAV group (all P < 0.05). Among 44 patients diagnosed with CAV by imaging examination, 24 cases were diagnosed with CAV by coronary CT angiography (CTA), 4 cases by coronary angiography (CAG), and 16 cases by coronary CTA combined with CAG. Among 44 patients, the proportion of grade Ⅰ CAV was 45% (20/44), 30% (13/44) for grade Ⅱ CAV and 25% (11/44) for grade Ⅲ CAV, respectively. All patients received long-term use of statins after operation, and 20 patients were given with antiplatelet drugs. Among 44 CAV patients, 11 patients underwent percutaneous coronary intervention, 6 cases received repeated heart transplantation, and 8 patients died. Kaplan-Meier survival analysis demonstrated that there was no significant difference in the long-term survival rate between the CAV and non-CAV groups (P > 0.05), whereas the survival rate of patients tended to decline after the diagnosis of CAV (at postoperative 6-7 years). The long-term survival rates of patients with grade Ⅰ, grade Ⅱ and grade Ⅲ CAV showed no significant difference (P > 0.05). Even for patients with grade Ⅰ CAV, the long-term survival rate tended to decline. Conclusions CAV is a common and intractable complication following heart transplantation, and the long-term survival rate of patients after the diagnosis of CAV tended to decline. Deepening understanding of CAV, prompt prevention, diagnosis and treatment should be delivered to improve the long-term survival rate of patients after heart transplantation.

Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo. To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti-H. pylori efficacy in the classical H. pylori-infected mice model. Therefore, the study provides a "comprehensive attack" strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.

OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.

OBJECTIVE To study the improvement effects of Huorongcaohuangqi （HRCHQ） admixture decoction on mesangial proliferative glomerulonephritis （MsPGN）model rats and its mechanism . METHODS Totally 70 rats were divided into sham operation group （n＝10）and modeling group （n＝60）according to body weight . Sham operation group underwent sham operation，and MsPGN model was induced by immunological method （Freund’s adjuvant+BSA+lipopolysaccharide ）in modeling group. After successfully modeling ，50 rats were randomly divided into model group ，HRCHQ high -dose，medium-dose and low - dose groups （4.05，2.03，1.02 g/kg），Benazepril hydrochloride tablet group （20 mg/kg），with 10 rats in each group . Sham operation group and model group were given distilled water intragastrically ；other groups were given relevant medicine intragastrically 15 mL/kg，once a day ，for consecutive 5 weeks. After last administration ，the contents of total protein ，albumin and urea nitrogen were determined in the serum of rats . The expressions of transforming growth factor β1（TGF-β1）and tumor necrosis factor α（TNF-α）in renal tissue were detected by immunohistochemistry ；the expression of complement C 3 in renal tissue was detected by immunofluorescence . The phosphorylation level of phosphatidylinositol 3 kinase/protein kinase B/glycogen synthase kinase 3β（PI3K/Akt/GSK-3β） signal pathway related proteins and expression level of fibronectin （FN） in renal tissue were detected by Western blot . RESULTS Compared with model group，the serum contents of total protein and albumin were increased significantly in HRCHQ high -dose group （P＜0.05 or P＜0.01）. The serum content of urea nitrogen ， the E-mail：Houxia_75@163.com expressions of TGF -β1，TNF-α，FN and complement C 3，and the phosphorylation levels of PI 3K，Akt and GSK 3β protein were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS HRCHQ can improve MsPGN by reducing the proliferation of mesangial cells and inhibiting the activity of PI 3K/ Akt/GSK3β signaling pathway .

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Objective:To evaluate the accuracy of glomerular filtration rate (GFR) assessed from the renal dynamic imaging method (Gates method) with 99Tc m-diethylene triamine pentoacetic acid (DTPA) in the heart transplant population. Methods:From September 2017 to June 2018, 34 patients with advanced heart failure who were prepared for surgery (30 males, 4 females; age: (45±14) years; heart transplant group) and 41 patients with normal heart function (19 males, 22 females; age: (50±17) years; control group) in Fuwai Hospital were respectively enrolled. GFRs of all patients were measured using Gates method (gGFR) and dual plasma sample method (DPSM; dGFR) with 99Tc m-DTPA. The accuracy of Gates method for detecting GRF was verified by using DPSM as the reference. Seventeen patients in heart transplant group underwent 99Tc m-DTPA renal dynamic imaging for Gates and DPSM results repeatedly after the surgery. The single kidney (left and right) functions (dGFRL and dGFRR) of DPSM were obtained according to the results of Gates method. Pearson correlation analysis and paired t test were used to analyze the data. Results:The gGFR in heart transplant group was higher than dGFR ((66.49±15.66) vs (49.16±13.24) ml·min -1·1.73 m -2; t=6.728, P<0.01), and there was a moderate correlation between them ( r=0.467, P<0.01). No difference between gGFR and dGFR in control group was observed ((65.35±26.28) vs (62.22±21.37) ml·min -1·1.73 m -2; t=1.268, P=0.212), and there was a good correlation between them ( r=0.799, P<0.01). The difference between 2 correlation coefficients was statistically significant ( z=-2.44, P<0.05). Serum creatinine decreased, while dGFR, dGFRL and dGFRR increased after the surgery, suggesting the improved renal function. Conclusions:The renal dynamic imaging method (Gates method) with 99Tc m-DTPA has less accuracy in the heart transplant patients. Combination of DPSM and Gates method can provide the precise total GFR and assess single kidney GFR, and may serve as a tool to monitor the renal function for the heart transplant patients in clinic.

Objective:To examine the prospective association of pubertal timing and tempo with depressive symptoms in adolescents.Methods:Since 2013, 2 084 students in grade 1-3 were selected from two primary schools in Bengbu, Anhui Province were selected by using convenience sampling method to establish the adolescence pubertal development cohort. Followed up for 6 years, physical examination, secondary sexual development evaluation (testicular volume for boys and breast development for girls) and depressive symptoms were evaluated biennially. Non-linear growth model was used to estimate pubertal timing and tempo for boys and girls respectively. Depressive symptoms were interviewed by using the Short Mood & Feeling Questionnaire (SMFQ) at baseline and Mood & Feeling Questionnaire (MFQ) during follow-up for students in grade 1-2. Children Depression Inventory (CDI) was used for students in grade 3 at baseline and during follow-up. Depressive symptom scores were standardized by using the Z-score method. Multivariate linear regression model was used to analyze the predictive effects of modeling pubertal timing and tempo on depressive symptoms of adolescence boys and girls. Results:There were 1 909 students with complete questionnaire and puberty development information, including 1 052 boys (59.19%) and 857 girls (43.81%), with average age about (13.94±0.87) years and 91.60 percent follow-up rate. The average modeling pubertal timing of girls (11.25 years) was earlier than that of boys (12.70 years), and the average pubertal tempo of girls about 1.47 Tanner stage/year was faster than that of boys about 1.28 Tanner stage/year. After controlling for depressive symptoms, maternal education and adverse childhood experiences at baseline and age, body mass index (BMI) classification and sleep time during follow-up, this predictive effect of pubertal timing and tempo on depressive symptoms was only significant among girls. Compared with girls with on time pubertal timing, girls in the delay timing group had a lower level of depressive symptoms (β=-0.19, 95% CI:-0.34,-0.01). Compared with girls in average pubertal tempo group, the fast tempo group associated with an increasing risk of depressive symptoms (β =0.23, 95% CI: 0.05, 0.40), while the slow tempo group associated with an decreasing risk of depressive symptoms (β =-0.21, 95％ CI:-0.39,-0.03). Insignificant effects were found in puberty timing and tempo on depressive symptoms of boys ( P>0.05). Conclusion:Fast pubertal tempo increases the risk of development of depressive symptoms of adolescent girls. There is no predictive effect of pubertal timing and tempo on depression symptoms of adolescent boys.

Objective:To examine the prospective association of pubertal timing and tempo with depressive symptoms in adolescents.Methods:Since 2013, 2 084 students in grade 1-3 were selected from two primary schools in Bengbu, Anhui Province were selected by using convenience sampling method to establish the adolescence pubertal development cohort. Followed up for 6 years, physical examination, secondary sexual development evaluation (testicular volume for boys and breast development for girls) and depressive symptoms were evaluated biennially. Non-linear growth model was used to estimate pubertal timing and tempo for boys and girls respectively. Depressive symptoms were interviewed by using the Short Mood & Feeling Questionnaire (SMFQ) at baseline and Mood & Feeling Questionnaire (MFQ) during follow-up for students in grade 1-2. Children Depression Inventory (CDI) was used for students in grade 3 at baseline and during follow-up. Depressive symptom scores were standardized by using the Z-score method. Multivariate linear regression model was used to analyze the predictive effects of modeling pubertal timing and tempo on depressive symptoms of adolescence boys and girls. Results:There were 1 909 students with complete questionnaire and puberty development information, including 1 052 boys (59.19%) and 857 girls (43.81%), with average age about (13.94±0.87) years and 91.60 percent follow-up rate. The average modeling pubertal timing of girls (11.25 years) was earlier than that of boys (12.70 years), and the average pubertal tempo of girls about 1.47 Tanner stage/year was faster than that of boys about 1.28 Tanner stage/year. After controlling for depressive symptoms, maternal education and adverse childhood experiences at baseline and age, body mass index (BMI) classification and sleep time during follow-up, this predictive effect of pubertal timing and tempo on depressive symptoms was only significant among girls. Compared with girls with on time pubertal timing, girls in the delay timing group had a lower level of depressive symptoms (β=-0.19, 95% CI:-0.34,-0.01). Compared with girls in average pubertal tempo group, the fast tempo group associated with an increasing risk of depressive symptoms (β =0.23, 95% CI: 0.05, 0.40), while the slow tempo group associated with an decreasing risk of depressive symptoms (β =-0.21, 95％ CI:-0.39,-0.03). Insignificant effects were found in puberty timing and tempo on depressive symptoms of boys ( P>0.05). Conclusion:Fast pubertal tempo increases the risk of development of depressive symptoms of adolescent girls. There is no predictive effect of pubertal timing and tempo on depression symptoms of adolescent boys.