Abstract Asthma is a well-characterized heterogeneous disease marked by airway remodeling and chronic airway inflammation. Clinically, the treatment of asthma primarily relies on hormonal drugs. However, the long-term use of these medications can lead to significant side effects. Mitophagy is a biological process that selectively transports damaged mitochondria to lysosomes for degradation. Recent research has revealed the crosstalk between mitophagy and asthma. Accordingly, taking mitophagy as an entry point, summarizing the key molecular mechanisms and regulators of mitophagy in asthma will facilitate the development of novel intervention targets and strategies for asthmatic treatment.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

In order to explore MYB transcription factors related to developmental processes and secondary metabolism in Morinda officinalis, we analyzed MoMYB expression based on transcriptome data from three tissues (root, stem and leaf). We used this analysis to provide a theoretical foundation for regulating the metabolism of M. officinalis. RNA-seq data along with the five databases including PFAM and plantTFDB and others were used to screen and classify MoMYB, including GO functional annotation and classification, subcellular localization, signal peptide prediction, conserved motif discovery, and comparative phylogenetic analysis. RT-qPCR was carried out to detect tissue-specific expression differences of MoMYB genes. According to transcriptome data, 109 MoMYB sequences were identified and divided into four classes, containing 51 sequences related to R2R3-MYB. Subcellular localization analysis indicated that a majority of sequences were located in nucleus. Blast2GO analysis showed that 109 MoMYB sequences were classified into three major functional ontologies including molecular function (112), biological processes (76) and cellular components (239). The R2-MYB conserved motif of 51 R2R3-MYB sequences possessed three significantly conserved tryptophan residues, whereas a phenylalanine replaced the first tryptophan in R3-MYB. The results of multiple sequence alignment and phylogenetic analysis revealed that the R2R3-MYB was distributed in all subgroups, apart from the S10, S19 and S21 subgroups. RT-qPCR indicated that several R2R3-MYB genes were differentially expressed among the three tissues, and this finding was consistent with transcriptome data. The 109 MoMYB sequences were annotated and divided into different classes, which lays the foundation for further study on MYB transcriptional factors in M. officinalis.

Objective To analyze the clinical features and NDP gene variants in patients with Norrie disease and familial exudative vitreoretinopathy,(FEVR).Methods Sixteen patients who were diagnosed as FEVR and 3 patients who were diagnosed as Norrie disease underwent detailed ocular examinations in Beijing Tongren Hospital from 2012 to 2018.Peripheral venous blood was drawn from patients and their family members for extration of genomic DNA.All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments.This study was approved by Joint Committee on Clinical Investigation of Beijing Tongren Hospital,and patients information and venous blood collection were done after the informed consents were obtained.Results Four unreported NDP gene mutations were detected in one FEVR patient and 3 Norrie disease patients:c.217T＞C (p.S73P),c.2T＞C (p.M1),c.194G＞T (p.C65F) and c.384C＞G (p.C128W).One patient who was clinically diagnosed as FEVR had no symptom but the avascular zone on the bilateral peripheral retina.The three Norrie disease patients who were clinically diagnosed as Norrie disease all appearred to have bilateral congenital blindness,mass in the vitreous and retinal detachment,and one in the three Norrie disease patient had evident mental retardation.Conclusions The results of this paper extend NDP gene mutation spectrum,and NDP gene is further confirmed to be the casuse of Norrie disease.

Objective Few studies have paid attention to time-zero renal biopsy in living kidney transplantation so far. This article aimed to investigate the risk factors of latent pathologic changes in living donors by time-zero renal biopsy (TO-RBx) and the predictive value in the allograft function of recipients early after living kidney transplantation.Methods We retrospectively analysed the clinical data of 89 renal transplant recipients and living donors who received TO-RBx at Nanjing General Hospital from January 2008 to December 2016. According to the 2007 Banff criteria, the common pathologic changes in living donors such as latent glomeruloscerosis (GS), tubular atrophy (CT), interstitial fibrosis (CI), arteriolar hyaline thickening (AH) and vascular fibrous intimal thickening (CV) were scored. To analyze the influencing factors for different pathological changes and evaluate its predictive value in the allograft function of recipients in 1, 3, 6 months after living renal transplantation.Results Of all the TO-RBx specimens, 23 cases (25.84%) with GS (21 were mild change, 1 was moderate change and 1 was severe change), 33 cases (37.08%) with CT/CI changes (30 were mild change and 3 were moderate change) and 37 cases (41.57%) with AH/CV changes (36 were mild change and 1 was moderate change). GS was related to the donor age (P=0.042); CT/CI changes were related to donor age, gender and systolic pressure (P=0.019；0.006；0.01); arterial changes were related to donor gender and blood triglyceride level (P=0.029；0.049). Within 3 and 6 months after living donor renal transplantation, the eGFR of renal transplant recipients with GS lesions \[(65.96±17.17), (69.52±19.1)mL/min·1.73m2\] were significantly lower than the groups without lesions \[(76.91±18.98), (79.52±18.91)mL/min·1.73m2\] (P＜0.05).Conclusion Time-zero renal biopsy has significance in terms of predicting the allograft function in 6 months after transplantation. It can guide the formulation and adjustment of postoperative immunosuppressive regimens for recipients. Besides, it can also detect the latent pathologic changes in living donors and is one of the important evidence for establishing a personalized follow-up plan for donors after surgery. This method is practical in clinical.

Objective: To explore the effect and specific mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis, and aim to provide a new idea on treating the disease with traditional Chinese medicine based on syndrome differentiation. Methods: A total of 60 C57BL/6J male rats were included in the study. The model of Qi deficiency and blood stasis was established in 60 rats by using multiple-factor stimulation. About 10 rats were randomly taken to verify whether the model establishment was successful and the rest of 50 rats were divided into 5 groups with 10 rats each: blank control group, cisplatin group, low dose group, medium dose group and high dose group. The blank control group was treated with normal saline, and cisplatin group was treated with cisplatin while the other three groups were treated with lung-tonifying and expectorant decoction at different doses. The volume change in transplanted tumor, tumor inhibition rate, apoptosis rate, and expression of Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 in 5 groups were compared. Results: The rapidest growth rate of transplanted tumor volume was observed in blank control group and the slowest in cisplatin group. The growth rate was gradually decreased with the increasing dose of lung-tonifying and expectorant decoction, and the difference in growth of tumor volume among groups was statistically significant (P < 0.05). The cisplatin group showed the highest tumor inhibition rate, with dose-dependent increase (P < 0.05). The apoptosis rate in low dose group was higher than blank control group but lower than high dose group (P < 0.05). The apoptosis rate in medium dose group was significantly higher than blank control group (P < 0.05). The apoptosis rate in high dose group was significantly higher than control group (P < 0.05). The positive expression rates of Bcl-2 and Bax in all groups showed statistically significant difference (P < 0.05), while expression of cleaved caspase-3 and cleaved caspase-9 in 5 groups was significantly different, with dose-dependent increase (P < 0.05). Conclusions: The lung-tonifying and expectorant decoction inhibits the proliferation of tumor cells by inducing and activating the cell apoptosis in treatment of lung cancer with Qi deficiency and blood stasis, probably with good clinical therapeutic effect.

Bipolar Disorder ; blood ; immunology ; metabolism ; Depressive Disorder ; blood ; immunology ; metabolism ; Humans ; Proteomics

The study of hemodynamics, which refers to dynamics inside the blood circulation, mainly includes the flow rate, flow resistance, pressure, shear stress, disturbed flow, as well as their associations in between. Therefore, with its important significance in the clinical treatments of vessel curvature, arterial stenosis or occlusion, pathological artery branches and aneurism, study about hemodynamics is essential to human health. Currently, extensive researches on hemodynamics have been conducted with respect to artery bypass, coronary arterial stenosis, abdominal aortic aneurysm, atherosclerosis, cerebral aneurysm and swirling flow. With the development of such research on hemodynamics, surgical planning and interventional therapy have improved rapidly. The influence mechanism of hemodynamic parameters, including pressure, flow resistance, flow rate, wall shear stress, blood viscosity, flow separation, turbulent flow, vortex on the post-operation complications could be deeply explored with the help of more and more clinical apparatus and have gained some achievements.

OBJECTIVETo evaluate the learning curve of complete mesocolic excision(CME) for colon cancer.

METHODSClinical data of 75 cases in whom CME was performed by a group of surgeons in the Department of Gastrointestinal Surgery, Peking University People's Hospital from November 2009 to June 2011 were reviewed. The patients were divided into three groups(groups A, B, C, 25 cases in each group) by operative chronologic sequence.

RESULTSThere were no significant differences in age, sex, preoperative staging, cancer location, operation history of abdomen, ASA among the three groups(P>0.05). The operative time in group A was (205.4 ± 53.2) min and decreased to (180.4 ± 29.7) min in group B and (169.8 ± 41.3) min in group C (P<0.05). The postoperative hospital stay decreased from (17.8 ± 10.9) d in group A to(12.9 ± 4.1) d in group B and(11.0 ± 3.5) d in group C(P<0.05). The postoperative complication rate decreased from 32%(8/25) in group A and 36%(9/25) to 8%(2/25) in group C. The specimen quality was superior in group C compared to group A (WEST grade C above were 20 and 11 respectively, P<0.05). There were no significant differences in intraoperative bleeding, time to first flatus, postoperative fasting time, number of retrieved lymph nodes among the three groups(P>0.05).

CONCLUSIONFrom the learning curve of CME, surgeons can learn CME skill after performing 25 cases.

Adult ; Aged ; Aged, 80 and over ; Colectomy ; education ; methods ; Colonic Neoplasms ; surgery ; Female ; Humans ; Learning Curve ; Male ; Mesocolon ; surgery ; Middle Aged ; Retrospective Studies ; Young Adult