1.Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.
Jia-Ying HU ; Zhen-Zhe LIN ; Li DING ; Zhi-Xing ZHANG ; Wan-Ling HUANG ; Sha-Sha HUANG ; Bin LI ; Xiao-Yan XIE ; Ming-De LU ; Chun-Hua DENG ; Hao-Tian LIN ; Yong GAO ; Zhu WANG
Asian Journal of Andrology 2025;27(2):254-260
Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans
;
Male
;
Azoospermia/diagnostic imaging*
;
Deep Learning
;
Testis/pathology*
;
Retrospective Studies
;
Adult
;
Ultrasonography/methods*
;
Sperm Retrieval
;
Sertoli Cell-Only Syndrome/diagnostic imaging*
2.High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.
Xiaojuan CHAO ; Mengwei NIU ; Shaogui WANG ; Xiaowen MA ; Xiao YANG ; Hua SUN ; Xujia HU ; Hua WANG ; Li ZHANG ; Ruili HUANG ; Menghang XIA ; Andrea BALLABIO ; Hartmut JAESCHKE ; Hong-Min NI ; Wen-Xing DING
Acta Pharmaceutica Sinica B 2024;14(1):190-206
Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.
3.Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cra-nial Sutures in Northern Chinese Han Adults
Xuan WEI ; Yu-Shan CHEN ; Jie DING ; Chang-Xing SONG ; Jun-Jing WANG ; Zhao PENG ; Zhen-Hua DENG ; Xu YI ; Fei FAN
Journal of Forensic Medicine 2024;40(2):128-134,142
Objective To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation(MPR),and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population.Methods The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected.Volume reconstruction(VR)and MPR were performed on the skull,and 160 cranial suture tomography images were generated for each sample.Then the MPR images of cranial sutures were scored according to the closure grading criteria,and the mean closure grades of sagittal suture,coronal sutures(both left and right)and lambdoid sutures(both left and right)were calculated respectively.Finally taking the above grades as independent variables,the linear regression model and four machine learning models for age estimation(gradient boosting regression,support vector regression,decision tree regression and Bayesian ridge regression)were established for northern Chinese Han adults age estimation.The accu-racy of each model was evaluated.Results Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest.All four machine learning models had higher age estimation accuracy than linear regression model.The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years.Conclusion The combination of skull CT-MPR and machine learning model can be used for age esti-mation in northern Chinese Han adults,but it is still necessary to combine with other adult age estima-tion indicators in forensic practice.
4.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
5.Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia.
Yi WANG ; Qiu Ying GAO ; Hui WANG ; Ding ZHANG ; Ying GAO ; Ying Di MIAO ; Xin Hui ZHAI ; Xing Xing HU ; Xin Li RU ; Wei Hua ZHANG
Chinese Journal of Hematology 2023;44(10):800-804
Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.
Male
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Humans
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Adult
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Middle Aged
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Female
;
Receptors, Chimeric Antigen/genetics*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
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Immunotherapy, Adoptive
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
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Cell- and Tissue-Based Therapy
6.Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.
Yue GAO ; Chun-Jie LIU ; Hua-Yi LI ; Xiao-Ming XIONG ; Gui-Ling LI ; Sjors G J G IN 'T VELD ; Guang-Yao CAI ; Gui-Yan XIE ; Shao-Qing ZENG ; Yuan WU ; Jian-Hua CHI ; Jia-Hao LIU ; Qiong ZHANG ; Xiao-Fei JIAO ; Lin-Li SHI ; Wan-Rong LU ; Wei-Guo LV ; Xing-Sheng YANG ; Jurgen M J PIEK ; Cornelis D DE KROON ; C A R LOK ; Anna SUPERNAT ; Sylwia ŁAPIŃSKA-SZUMCZYK ; Anna ŁOJKOWSKA ; Anna J ŻACZEK ; Jacek JASSEM ; Bakhos A TANNOUS ; Nik SOL ; Edward POST ; Myron G BEST ; Bei-Hua KONG ; Xing XIE ; Ding MA ; Thomas WURDINGER ; An-Yuan GUO ; Qing-Lei GAO
Protein & Cell 2023;14(6):579-590
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans
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Female
;
Blood Platelets/pathology*
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Biomarkers, Tumor/genetics*
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Ovarian Neoplasms/pathology*
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China
7.The role of Huaiqihuang Granules in the long-term management of bronchial asthma in young children: a multicenter real-world study
Huimin WANG ; Jinghui MU ; Chuanhe LIU ; Changshan LIU ; Ying WANG ; Zhiying HAN ; Xin SUN ; Xing CHEN ; Shuhua AN ; Dolikon MUZAPAR ; Aiping LU ; Min WANG ; Yan CHENG ; Xiaomei YIN ; Hanmin LIU ; Hong WANG ; Shan HUA ; Li DONG ; Ying HUANG ; Yi JIANG ; Jianxin XIONG ; Shenggang DING ; Wei WANG ; Shunying ZHAO ; Yuzhi CHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(4):286-290
Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.
8.Mechanism of Bushen Zhuyun Prescription on Improving Luteal Function of Brown Norway Rats Based on MAPKs Signaling Pathway
Xing-ran TANG ; Hui-fang ZHOU ; Hua FENG ; Yu-jie SHANG ; Yi-zhen YUAN ; Ya-xin DAI ; Yin-yin DING
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(12):78-85
ObjectiveTo investigate the possible mechanism of Bushen Zhuyun prescription (BSZYP) to reduce the level of ovarian apoptosis in Brown Norway (BN) rats with luteal phase deficiency (LPD). MethodFifty SPF female BN rats were randomly divided into a model group, a dydrogesterone group (0.002 g·kg-1), and a low (4.5 g·kg-1), a medium (9 g·kg-1), and a high-dose (18 g·kg-1) BSZYP groups, with ten rats in each group. The rats were administrated with corresponding drugs by gavage, once a day for three estrus cycle. Western blot was used to detected the protein expression levels of c-Jun NH2 terminal kinase (JNK), extracellular signal-regulated kinase (ERK), phosphorylated-ERK (p-ERK), phosphorylated-JNK (p-JNK), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated-p38 MAPK (p-p38 MAPK ), B-cell lymphoma (Bcl-2), and Bcl-2 associated X protein (Bax) in ovary. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of ERK, JNK, p38 MAPK, Bax, and Bcl-2 in ovary. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum progesterone (P) and estradiol (E2) levels. Hematoxylin-eosin (HE) staining was used to observe the ovarian tissue morphology. ResultCompared with the model group, the recovery of estrus cycle of rats in all BSZYP groups had statistical significance after 1-circle administration (P<0.05). The ovarian tissue morphology in the low-dose BSZYP group was improved, and that in the medium and high-dose BSZYP groups was significantly improved with clear follicle, less vesicular follicle and atretic follicle, and more granular layers. The number of luteum, especially the fresh luteum, in the medium and high-dose groups was increased with smooth edge and large volume. The mRNA expression level of Bcl-2 was increased in all-dose BSZYP groups, while the mRNA expression level of Bax was significantly decreased in all-dose BSZYP group (P<0.05, P<0.01). The mRNA expression levels of JNK and p38 MAPK were significantly decreased in the high-dose BSZYP group (P<0.01), and the mRNA expression levels of ERK were increased in the low and medium-dose BSZYP groups (P<0.05). The protein expression level of Bcl-2 was significantly increased in the medium and high-dose BSZYP groups (P<0.01), and the protein expression level of Bax was significantly decreased in the all-dose BSZYP groups (P<0.01). No significant difference was observed in the protein expressions of JNK, ERK, and p38 MAPK in the BSZYP groups. The protein expression levels of p-ERK in the ovarian tissues of rats were significantly inoreased in the medium and high-dose BSZYP group (P<0.01), p-JNK, and p-p38 MAPK in the ovarian tissues of rats were significantly decreased in the medium and high-dose BSZYP group (P<0.01). The level of E2 was increased in all-dose BSZYP groups (P<0.05, P<0.01), and the level of P in the medium-dose BSZYP group was increased (P<0.05). ConclusionBSZYP improved the serum sex hormones, restored the estrous cycle, reduced atretic follicle and vesiculation, and maintained luteal morphology and function of BN rats, so as to improve luteal function and treat luteal phase deficiency. The mechanism of BSZYP may be related to reduce the level of ovarian tissue apoptosis in BN rats by regulating MAPKs signaling pathway.
9.Expression and Significance of PD-1 and ICOS in Patients with Primary Immune Thrombocytopenia.
Zi FU ; Wen QU ; Zong-Hong SHAO ; Hua-Quan WANG ; Li-Min XING ; Xi-Feng DONG ; Zhao-Yun LIU ; Xiao-Na LI ; Yang ZHANG ; Shao-Xue DING
Journal of Experimental Hematology 2022;30(4):1170-1175
OBJECTIVE:
To investigate the expression of programmed death receptor-1 (PD-1) and inducible costimulator (ICOS) on the surface of CD8+ T cells in peripheral blood of patients with primary immune thrombocytopenia (ITP), and explore the roles of PD-1 and ICOS in the occurrence and development of ITP.
METHODS:
A total of 28 ITP patients treated in Tianjin Medical University General Hospital from September to December 2020 were selected, including 13 patients with newly diagnosed ITP, 15 patients with chronic ITP, and 22 healthy volunteers were recruited as control group. Flow cytometry was used to detect the expression levels of PD-1 and ICOS, and evaluate their correlation with clinical indicators.
RESULTS:
The percentage of CD8 + T cells in ITP patients of chronic group was higher than that of the newly diagnosed group and the control group (P<0.05). The expression level of PD-1 on CD8+ T cells in ITP patients of newly diagnosed group and chronic group were significantly lower than that of the control group (P<0.05), while the expression level of ICOS were significantly higher (P<0.05). In ITP patients, PD-1 was negatively correlated with platelet count (r=-0.4942, P<0.01), but positively with ICOS (r=0.4342). PD-1 and ICOS were both negatively correlated with lymphocyte count (rPD-1=-0.4374; rICOS=-0.4492).
CONCLUSION
In ITP patients, the unbalanced expression of PD-1 and ICOS may interfere with the immune homeostasis of the body, which can be used as a therapeutic target for ITP patients.
CD8-Positive T-Lymphocytes/metabolism*
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Flow Cytometry
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Humans
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Inducible T-Cell Co-Stimulator Protein/metabolism*
;
Platelet Count
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Programmed Cell Death 1 Receptor/metabolism*
;
Purpura, Thrombocytopenic, Idiopathic
10.Summary of the 17th Chinese Symposium on Burn Medicine and the 2022 Congress of Burn Medicine Branch of China International Exchange and Promotion Association for Medical and Healthcare, and the 12th Academic Conference on Burn and Plastic Surgery in Five Provinces and One City in Southwest China.
Hua Rong DING ; Jin Jin JIA ; Yu MO ; Wei Feng HE ; Gao Xing LUO ; De Hui LI ; Guang Ping LIANG
Chinese Journal of Burns 2022;38(9):897-898
The 17th Chinese Symposium on Burn Medicine and the 2022 Congress of Burn Medicine Branch of China International Exchange and Promotion Association for Medical and Healthcare, and the 12th Academic Conference on Burn and Plastic Surgery in Five Provinces and One City in Southwest China was successfully held in green city Nanning, from August 25th to 27th, 2022. The conference theme was "Burn treatment and wound repair", received nearly 200 submissions, nearly 1 100 online and offline registered delegates, and nearly 300 offline attendees. The meetings were held in one main venue and three branch venues, with combination of speaking offline and live and recorded broadcast, as well as whole process synchronous live broadcasting. During the meeting, key issues about burn treatment and wound repair were discussed, with warm academic atmosphere.
Burns/surgery*
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China
;
Delivery of Health Care
;
Humans
;
Plastic Surgery Procedures
;
Surgery, Plastic

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