Photo-Induced Disproportionation-Mediated Photodynamic Therapy: Simultaneous Oxidation of Tetrahydrobiopterin and Generation of Superoxide Radicals.

We herein present an approach of photo-induced disproportionation for preparation of Type-I photodynamic agents. As a proof of concept, BODIPY-based photosensitizers were rationally designed and prepared. The photo-induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4 ), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2 - ⋅). One of our Type-I photodynamic agents not only self-assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2 ), with a half-maximal inhibitory concentration (IC50 ) of 0.96 µM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors.

Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.@*METHODS@#Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.@*RESULTS@#Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter -42 bp to -28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Ultra-Small Nano-Assemblies as Tumor-Targeted and Renal Clearable Theranostic Agent for Photodynamic Therapy.

It is a challenge to design photosensitizers to balance between the tumor-targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. Herein, an ultra-small nano-photosensitizer 1a with excellent tumor-specific accumulation and renal clearance is reported. It is formed from the self-assembly of compound 1 bearing three triethylene glycol (TEG) arms and two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal-to-background ratio reaching as high as 11.5 after tail intravenous injection. The ultra-small size of 1a with an average diameter of 5.6 nm allows its fast clearance through kidney. Self-assembly also endows 1a with an 18.2-fold enhancement of reactive oxygygen species generation rate compared to compound 1 in organic solution. Nano-PS 1a manifests an excellent photodynamic therapy efficacy on tumor-bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor-targeting ability.

Supramolecular Photosensitizer Enables Oxygen-Independent Generation of Hydroxyl Radicals for Photodynamic Therapy.

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical (•OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic •OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivo antitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.

Research progress in anti-reflux reconstructions and mechanism after proximal gastrectomy / 中华胃肠外科杂志

The electrophysiological activity of the gastrointestinal tract and the mechanical anti-reflux structure of the gastroesophageal junction are the basis of the anti-reflux function of the stomach. Proximal gastrectomy destroys the mechanical structure and normal electrophysiological channels of the anti-reflux. Therefore, the residual gastric function is disordered. Moreover, gastroesophageal reflux is one of the most serious complications. The emergence of various types of anti-reflux surgery through the mechanism of reconstructing mechanical anti-reflux barrier and establishing buffer zone, and the preservation of, the pacing area and vagus nerve of the stomach, the continuity of the jejunal bowel, the original gastroenteric electrophysiological activity of the gastrointestinal tract, and the physiological function of the pyloric sphincter, are all important measures for gastric conservative operations. There are many types of reconstructive approaches after proximal gastrectomy. The design based on the anti-reflux mechanism and the functional reconstruction of mechanical barrier, and the protection of gastrointestinal electrophysiological activities are important considerations for the selected of reconstructive approaches after proximal gastrectomy. In clinical practice, we should consider the principle of individualization and the safety of radical resection of tumor to select a rational reconstructive approaches after proximal gastrectomy.

Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics / 中国中药杂志

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

Clinical study of the relationship between cellular adhesion molecules and left ventricular geometry and function in patients with obstructive sleep apnea syndrome and prehypertension / 中华超声影像学杂志

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

Engineering and application of Komagataella phaffii as a cell factory / 生物工程学报

Nowadays, engineered Komagataella phaffii plays an important role in the biosynthesis of small molecule metabolites and protein products, showing great potential and value in industrial productions. With the development and application of new editing tools such as CRISPR/Cas9, it has become possible to engineer K. phaffii into a cell factory with high polygenic efficiency. Here, the genetic manipulation techniques and objectives for engineering K. phaffii are first summarized. Secondly, the applications of engineered K. phaffii as a cell factory are introduced. Meanwhile, the advantages as well as disadvantages of using engineered K. phaffii as a cell factory are discussed and future engineering directions are prospected. This review aims to provide a reference for further engineering K. phaffii cell factory, which is supposed to facilitate its application in bioindustry.

A novel CRISPR/Cas9-hLacI donor adapting system for dsDNA-templated gene editing / 生物工程学报

During the gene editing process mediated by CRISPR/Cas9, precise genome editing and gene knock-in can be achieved by the homologous recombination of double-stranded DNA (dsDNA) donor template. However, the low-efficiency of homologous recombination in eukaryotic cells hampers the development and application of this gene editing strategy. Here, we developed a novel CRISPR/Cas9-hLacI donor adapting system (DAS) to enhance the dsDNA-templated gene editing, taking the advantage of the specific binding of the LacI repressor protein and the LacO operator sequence derived for the Escherichia coli lactose operon. The codon-humanized LacI gene was fused as an adaptor to the Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus lugdunensis Cas9 (SlugCas9-HF) genes, and the LacO operator sequence was used as the aptamer and linked to the dsDNA donor template by PCR. The Cas9 nuclease activity after the fusion and the homology-directed repair (HDR) efficiency of the LacO-linked dsDNA template were firstly examined using surrogate reporter assays with the corresponding reporter vectors. The CRISPR/Cas9-hLacI DASs mediated genome precise editing were further checked, and we achieved a high efficiency up to 30.5% of precise editing at the VEGFA locus in HEK293T cells by using the CRISPR/SlugCas9-hLacI DAS. In summary, we developed a novel CRISPR/Cas9-hLacI DAS for dsDNA-templated gene editing, which enriches the CRISPR/Cas9-derived gene editing techniques and provides a novel tool for animal molecular design breeding researches.

Supramolecular photodynamic agents for simultaneous oxidation of NADH and generation of superoxide radical.

Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare Type-I PSs is of great importance, but remains a challenge. Here, we report a supramolecular strategy for the preparation of Type-I photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors to the existing Type-II PSs. As a proof-of-concept, three electron acceptors were designed and co-assembled with a classical PS to produce quadruple hydrogen-bonded supramolecular photodynamic agents. The photo-induced electron transfer from the PS to the adjacent electron acceptor occurs efficiently, leading to the generation of a strong oxidizing PS+• and an anionic radical of the acceptor, which further transfers an electron to oxygen to form O2-•. In addition, these photodynamic agents induce direct photocatalytic oxidation of NADH with a turnover frequency as high as 53.7 min-1, which offers an oxygen-independent mechanism to damage tumors.

A host-guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator.

Type-I photosensitizers (PSs) generate cytotoxic oxygen radicals by electron transfer even in a hypoxic environment. Nevertheless, the preparation of type-I PSs remains a challenge due to the competition of triplet-triplet energy transfer with O2 (type-II process). In this work, we report an effective strategy for converting the conventional type-II PS to a type-I PS by host-guest complexation. Electron-rich pillar[5]arenes are used as an electron donor and macrocyclic host to produce a host-guest complex with the traditional electron-deficient type-II PS, an iodide BODIPY-based guest. The host-guest complexation promotes intermolecular electron transfer from the pillar[5]arene moiety to BODIPY and then to O2 by the type-I process upon light-irradiation, leading to efficient generation of the superoxide radical (O2 -˙). The results of anti-tumor studies indicate that this supramolecular PS demonstrates high photodynamic therapy efficacy even under hypoxic conditions. This work provides an efficient method to prepare type-I PSs from existing type-II PSs by using a supramolecular strategy.

Circularly polarized luminescence from helical N,O-boron-chelated dipyrromethene (BODIPY) derivatives.

We report N,O-boron-chelated dipyrromethene derivatives exhibiting circularly polarized luminescence (CPL) in the red/near-infrared region, both in solution and the aggregated state. The CPL is originated from the helical chirality through intramolecular substitution of fluorine by an alkenolic substituent. The self-assembly of the fluorophores significantly enhances the |glum| values from 10-4 to 10-2.

Drug-coated balloon for in-stent restenosis in femoropopliteal segment: 1-year clinical outcomes from a multicenter study in China / 中华普通外科杂志

Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.

Risk factors of long-term mortality in patients with acute pulmonary embolism and the predictive value of echocardiography / 中华全科医师杂志

Objective:To investigate the risk factors of long-term mortality in patients with acute pulmonary embolism (APE) and to explore the predictive value of echocardiography.Methods:A total of 109 APE patients admitted in First Hospital of Shanxi Medical University between December 2010 and November 2014 were enrolled in this study. APE was diagnosed by computed tomography pulmonary angiography (CTPA) or ventilation-perfusion pulmonary scintigraphy. Transthoracic echocardiography (TTE) parameters and clinical parameters within 48 h of onset were collected. All the patients were treated with standard anticoagulation, thrombolysis, or thrombectomy. Regular follow-up was carried out, with the average follow-up period of (7.20±1.04) years. The patients were divided into survival group and fatal group according to their follow-up results. The echocardiographic parameters and primary biochemical laboratory parameters within 48 h after onset were compared between the survival group and the fatal group by t test or χ 2 test. Cox regression analysis was conducted to analyze the influencing factors of long-term prognosis of patients with APE. Survival analysis was performed in patients with echocardiographic assessment of right ventricular (RV) enlargement and/or dysfunction and without RV enlargement and/or dysfunction by Kaplan-Meier method, and the survival curves were plotted. The comparison between the two groups was performed by log-rank test. Results:The average follow-up period was (7.20±1.04) years. Fourteen patients were lost in the follow-up, and 95 patients were included in the final analysis, among whom 58 survived and 37 died with a fatality rate of 39.0%. Cox regression analysis showed that age ( HR=2.32, 95% CI:1.31-4.13, P=0.004), malignancy ( HR=6.49, 95% CI:2.32-18.14, P<0.001), right atrial (RA)/left atrial (LA) area ratio ( HR=2.01, 95% CI:1.16-3.48, P=0.013), RV enlargement and/or dysfunction ( HR=5.90, 95% CI: 1.45-23.94, P=0.013), Charlson comorbidity index (CCI) score ( HR=1.75, 95% CI: 1.04-2.96, P=0.035), low oxygen saturation ( HR=1.70, 95% CI:1.14-2.53, P=0.009) were independent risk factors associated with long-term mortality in patients with APE. Kaplan Meier survival curve analysis showed that the cumulative survival rates of patients with RV enlargement and/or dysfunction at 1, 3, 5 and 7 years were 92.8%, 66.7%, 59.4% and 52.2% respectively, and those without RV enlargement and/or dysfunction were 96.2%, 92.3%, 84.6% and 84.6%,respectively (log rank test, P=0.006). Conclusions:Patients with APE have high long-term mortality. Early echocardiographic RV enlargement and/or dysfunction, RA/LA area ratio, age, malignant tumor, CCI score and low oxygen saturation are independent risk factors related to long-term mortality in patients with APE. Ultrasound evaluation of patients with RV enlargement and/or dysfunction has a certain value in predicting long-term mortality in patients with pulmonary embolism.

BODIPY-Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen.

Developing Type-I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to design photosensitizers for generating reactive oxygen species by the Type-I process. Herein, we report a series of α,ß-linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2-. ) by the Type-I process upon light irradiation. The triplet formation originates from an effective excited-state relaxation from the initially populated singlet (S1 ) to triplet (T1 ) states via an intermediate triplet (T2 ) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2-. by inter-molecular charge transfer to molecular oxygen. The energy gap of T1 -S0 is smaller than that between 3 O2 and 1 O2 thereby precluding the generation of singlet oxygen by the Type-II process. The trimer exhibits superior PDT performance under the hypoxic environment.

A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus vectored vaccines expressing spike (S) protein have advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD) or dimeric tandem-repeat RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular (Th1-based) immune responses. AdC7-RBD-tr2 showed higher antibody responses compared with both AdC7-S and AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Analysis of hydroxylation and O-glycosylation on lysine sites in deer-hide gelatin / 中国中药杂志

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.

Enlightenment of COVID-19 epidemic on function and layout of China-Africa friendship hospital: from global health governance perspective / 中华医院管理杂志

The globalized epidemic of the COVID-19 forced the international community to reconsider the importance and urgency of global public health in world peace and development. The authors analyzed the COVID-19 epidemic prevention and control situation in Africa, and discussed the functions and layout of China-Africa friendship hospitals from the perspective of global health governance. It was suggested that the functions of China-Africa friendship hospitals should be positioned as the high-level medical centers in Africa, regional medical and disease control linkage centers, regional health technology training centers, regional telemedicine collaboration center, and regional health policy research center.Furthermore, the layout of China-Africa friendship hospitals should respond to China′s assistance in the construction of Africa′s center for disease control and China-Africa′s cooperation plan for promoting the " one belt and one road" construction, and work together with the medical team to build a new pattern of medical integration and health care system for African disease prevention and control and medical treatment.