1.Advances in the Application of Forensic Microbiome Analysis in Tissue Source Inference
Hewen YAO ; Chaoran SUN ; Shuangshuang WANG ; Yuxiang ZHOU ; Zhirui ZHANG ; Feng SONG ; Haibo LUO
Journal of Sichuan University (Medical Sciences) 2025;56(5):1419-1426
Forensic microbiology,a pivotal discipline within forensic science,focuses on microorganisms as the primary subject of study and applies life science technologies to analyze microbial evidence in criminal and civil investigations.Tissue source inference plays a crucial role in forensic investigations,facilitating case assessment and crime scene reconstruction.The application of microbiome analysis in tissue source inference benefits from the tissue specificity and spatiotemporal stability of human microbial communities.This article provides a systematic review of recent advances in tissue source inference based on microbiome analysis,covering technological development,research trends,and practical applications.Finally,the challenges confronted in practice in forensic microbiology and the future prospects for its development are summarized.
2.Clinical evidence mapping on postoperative recurrence of endometrial polyps by traditional Chinese medicine
Zhirui SUN ; Lu XUE ; Liuxinyue CHEN ; Shaobin WEI
Journal of Clinical Medicine in Practice 2025;29(20):101-108,118
Objective To sort out the distribution characteristics of literature evidences on tradi-tional Chinese medicine interventions for postoperative endometrial polyps(EPs),understand the current application status of traditional Chinese medicine in improving the postoperative status and preventing recurrence in patients with endometrial polyps,explore potential research directions,and summarize the deficiencies.Methods Clinical studies on traditional Chinese medicine treatment for EPs were searched in databases including China National Knowledge Infrastructure(CNKI),Wan-fang Data Knowledge Service Platform(WanFang),VIP Chinese Journal Service Platform(VIP),Chinese Biomedical Literature Database(SinoMed),Chinese Clinical Trial Registry(CHICTR),PubMed,Cochrane Library,Web of Science,Embase,and Clinical Trials.gov(CT.gov).The Chinese Medical Journal Full-text Database was also supplemented for retrieval.The search period spanned from the establishment of each database to January 2025.The basic characteristics,outcome indicators,and methodological quality assessments of the included studies were presented in graphical form.Results A total of 150 articles were included,comprising 4 systematic reviews/Meta-analyses,146 clinical studies,and 0 expert consensuses or clinical pathways.The clinical studies were predominantly two-arm trials with sample sizes concentrated between 60 and 120 cases.Oral administration of traditional Chinese medicine decoctions was the primary intervention,with treatment durations mostly lasting 3 months.Outcome indicators mainly included clinical efficacy,recurrence rate,and menstrual condi-tions,among others.However,the evaluation criteria were inconsistent,and patients' quality of life was neglected.Randomized controlled trials exhibited biases in blinding implementation,randomiza-tion processes,and outcome reporting.Non-randomized controlled trials faced issues with imbal-anced sample sizes between groups.Observational studies demonstrated biases in measuring expo-sure factors.Systematic reviews/Meta-analyses showed deficiencies in methodological and reporting quality.Conclusion Traditional Chinese medicine demonstrates advantages in improving the post-operative status and preventing recurrence in patients with endometrial polyps.Subsequent research should enhance the quality of study design and implementation,adopt objective outcome indicators,standardize efficacy criteria for traditional Chinese medicine syndromes,and improve the evidence quality of evidence-based medicine research.
3.Clinicopathological features and prognosis of IgA nephropathy with renal arteriolosclerosis
Weiyi GUO ; Xiuping AN ; Lijun SUN ; Hongrui DONG ; Xiaoyi XU ; Wenrong CHENG ; Guoqin WANG ; Nan YE ; Zhirui ZHAO ; Hong CHENG
Chinese Journal of Nephrology 2023;39(3):209-214
The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.
4.Molecular characterization of mutations associated with resistance among 72 multidrug-resistant strains of Mycobacterium tuberculosis by whole genome sequencing
MU Cheng ; SUN Rui ; WANG Zhirui ; ZHAO Hui ; WANG Chunhua
China Tropical Medicine 2023;23(7):725-
Abstract: Objective To understand the characteristics of mutations associated with resistance among 72 multidrug-resistant tuberculosis (MDR-TB) strains using whole genome sequencing (WGS) and to evaluate the performance of WGS for predicting MDR-TB drug resistance. Methods The clinical strains isolated from patients who visited the outpatient department of Tianjin Center for Tuberculosis Control from January to September in 2020 were collected. Identification tests using p-nitrobenzoic acid (PNB) medium were performed. Drug susceptibility tests (proportion method) on L-J medium were performed. After excluding duplicate strains, 72 MDR-TB strains were selected for WGS. Data were analyzed by using online databases and the phenotypic drug susceptibility test results were compared with resistance profiles predicted by WGS. Results All of 72 MDR-TB strains belonged to linage 2, and there was no significant difference in rate of pre-extensive drug-resistant tuberculosis (pre-XDR-TB) between modern type and ancestral type (χ2=0.287, P=0.592). A total of 81 mutation types were found from resistance-related genes for 12 anti-tuberculosis drugs, and the common mutation types in different drug-resistant strains were: streptomycin (SM): rpsL Lys43Arg; isoniazid (INH): katG Ser315Thr; rifampicin (RIF): rpoB Ser450Leu; ethambutol (EMB): embB Met306Val; ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX): gyrA Asp94Gly; kanamycin (KAM), capreomycin (CAP), amikacin (AMK): rrs 1401a>g; para-aminosalicylic acid (PAS): folC Ile43Thr. Nine mutation types were found in 9 prothionamide (PTO)-resistant strains, one type for each strain. The sensitivity and specificity of WGS for predicting resistance to different drugs were SM: 98.15% and 88.89%, INH: 90.28% and -, RIF: 98.62% and -, EMB: 79.49% and75.76%, OFX: 97.30% and 85.71%, KAM: 85.71% and 98.46%, PAS: 27.27% and 95.08%, PTO: 81.82% and 60.66%, CAP: 60.00% and 98.51%, LFX: 97.22% and 83.33%, MFX: 97.30% and 85.71%, AMK:100.00% and 100.00%, respectively. Conclusion WGS is a rapid and promising method which has high consistency with the phenotypic drug sensitivity test. Therefore, it has good application prospects in predicting drug resistance in MDR-TB.
5.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.
6.Role of complement activation in the pathogenesis of severe cardiorenal injury in patients with primary malignant hypertension
Xiaoyi XU ; Lijun SUN ; Hong CHENG ; Hongrui DONG ; Guoqin WANG ; Zhirui ZHAO
Chinese Journal of Nephrology 2022;38(2):115-125
Objective:To investigate the role of complement activation in the pathogenesis of primary malignant hypertension (MHT) with nephrosclerosis complicated with severe cardiorenal injury.Methods:Data of MHT patients with nephrosclerosis proven by biopsy from January 2010 to December 2020 in the Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. The expressions of complement-related component C4d, C1q, complement factor H-related protein 5, C3c and C5b-9 were detected by immunohistochemical staining. According to whether the patients were complicated with acute heart failure (AHF) and/or acute kidney injury (AKI), they were divided into severe cardiorenal injury group and non-severe cardiorenal injury group. The differences of clinicopathological data between the two groups were compared. According to the degree of C4d deposition in renal tissues, patients were divided into C4d diffused deposition group and non-C4d diffused deposition group. The severity of cardiorenal injury and the pathological characteristics of thrombotic microangiopathy in renal tissues were compared between the two groups.Results:A total of 33 patients were enrolled in this study, of which 17 cases (51.5%) were complicated with severe cardiorenal injury; AHF occurred in 16 patients (48.5%), AKI occurred in 8 patients (26.7%), and AHF and AKI were combined in 7 patients (21.2%). Compared with non-severe cardiorenal injury group, patients in severe cardiorenal injury group had higher levels of baseline lactate dehydrogenase [326.0 (217.0, 366.0) IU/L vs 197.0 (165.0, 220.0) IU/L, Z=37.000, P=0.002] and hemoglobin [(143.6±24.0) g/L vs (106.4±24.7) g/L, t=38.500, P<0.001], lower levels of 12 h urinary incontinence osmolality [400.0 (342.5, 504.0) mmol/L vs 476.0 (432.3, 616.5) mmol/L, Z=72.000, P=0.021] and serum albumin [(36.2±9.4) g/L vs (43.2±6.2) g/L, t=6.423, P=0.017], and thicker left ventricular posterior wall [(14.0±2.1) mm vs (12.1±1.1) mm, t=6.552, P=0.018]. The immunohistochemical results of kidney tissue showed that the proportions of C4d and C5b-9 diffused deposition in severe cardiorenal injury group were significantly higher than those in non-severe cardiorenal injury group (5/16 vs 0/15, P=0.043; 12/16 vs 5/15, P=0.032). Compared with non-C4d diffused deposition group, C4d diffused deposition group had higher incidence of AHF (5/5 vs 10/26, P=0.018), poorer heart function, more severe ventricular remodeling, and shorter history of hypertension [2.0 (0, 12.0) months vs 48.0 (9.5, 84.0) months, Z=22.500, P=0.022]. Conclusions:The incidence of severe cardiorenal injury in MHT patients with nephrosclerosis is about 51.5%. The proportion of diffuse deposition of complement activated components in renal tissues in patients with severe cardiorenal injury is higher than that in patients with non-severe cardiorenal injury. Overactivation of complement may be involved in the pathogenic process of severe heart and kidney injury caused by MHT.
7.Development Status of Irreversible Electric Perforated Tumor Ablation Device.
Tianshuai HE ; Kun TAN ; Qianqian SUN ; Zhirui ZHANG ; Xue CHEN ; Yi LYU ; Rongqian WU
Chinese Journal of Medical Instrumentation 2021;45(6):655-661
This study firstly introduced the mechanism, benefits and applications of irreversible electroporation(IRE) for tumor ablation. In addition, this study also introduced the most advanced IRE systems cleared by FDA or CFDA and IRE research equipment. The clinically licensed IRE systems include the Nanoknife 3.0 of Angiodynamics, the Dophi
Electricity
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Electroporation
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Heart Rate
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Humans
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Neoplasms/therapy*
8.Effects of tumor treating fields (TTF) arrays on the radiation doses to glioblastoma
Lei HAN ; Xiaoyang HU ; Lei SUN ; Jianying ZHANG ; Han XIAO ; Chunxia NI ; Zhirui ZHOU ; Yang WANG
Chinese Journal of Radiological Medicine and Protection 2021;41(9):685-689
Objective:To preliminarily explore the effects of tumor treating fields (TTF) arrays on the dose distribution in the treatment of Glioblastoma (GBM) using combined radiotherapy and concurrent TTF.Methods:EDR2 and MatriXX plate ionization chamber were employed to measure the absorbed doses of tissues at different depths (< 1 mm, 3 mm, 5 mm, 1 cm, 1.5 cm, 3 cm, 5 cm, 10 cm, and 15 cm) in the case that TTF arrays and latex-free foam were attached and not attached on the surface. Then the absorbed doses were calculated, compared, and analyzed. For the volumetric arc therapy (VMAT) of 10 GBM patients, deep dose verification was performed using the Sun Nuclear ArcCheck 3D dose verification system and the D99%, Dmean, and D1% of tumors and OARs were assessed. Results:The surface dose increased by 173% in the case that TTF arrays and latex-free foam were attached to the surface compared with the case of the surface with nothing attached. The surface dose increased by 61.7% due to the attachment of low-density latex-free foam. The dose deviation gradually decreased with an increase in the depth and stabilized (about 4%) at a depth of greater than 1.5 cm. As indicated by the VMAT verification result, the D99%, Dmean, and D1% of PTV and CTV decreased by 1.1%-1.2% and the Dmean and D1% of OARs (i.e., brainstem, pituitary gland, optic chiasma, optic nerve, eyeball, and eye crystal) decreased by 0.7%-1.5% in the case that TTF array and latex-free foam were attached on the surface compared with the case the surface with nothing attached. Conclusions:The combined radiotherapy and concurrent TTF in the GBM treatment will lead to a slight reduction of the absorbed doses of targets and OARs but a significant increase in the absorbed doses of the scalp. Therefore, it is recommended that the scalp doses should be reduced as far as possible in the design of the radiation treatment plan to reduce the adverse reactions on the scalp of GBM patients.
9.Study on the Effects of Deoxyschizandrin on the Proliferation ,Migration and Invasion of Human Nasopharyngeal Carcinoma Cell HONE- 1 via Met/PI 3K/Akt Signaling Pathway
Tengxiang CHEN ; Li LIANG ; Zhirui ZENG ; Shan LEI ; Jingya WANG ; Yuanmei SUN ; Jinzhi LAN ; Yan XUE
China Pharmacy 2020;31(19):2376-2381
OBJECTIVE:To study the effects and potential mechani sm of deoxyschizandrin on the proliferation ,migration and invasion of nasopharyngeal carcinoma cell HONE- 1. METHODS :HONE-1 cell was set as cell model ,while CCK- 8 test,wound healing assay and Transwell chamber test were used to detect the proliferation ,migration and invasion ability changes of HONE- 1 cells after treatment with different concentrations [ 0(blank control ),10,20,40 μmol/L] of deoxyschizandrin. Computer molecular docking was performed to analyze the binding ability between deoxyschizandrin and Met protein. Western blotting assay was used to detect the relative protein expressions of p-Met ,p-PI3K,p-Akt,Bcl-2 and N-cadherin in cells. RESULTS :Compared with blank control ,the proliferation ,migration and invasion ability of cells after treated with 10,20,40 μmol/L deoxyschizandrin were all decreased significantly (P<0.05). Results of molecular docking revealed that deoxyschizandrin could stably bind with the activity pocket of Met protein. Results of Western blotting assay demonstrated that compared with blank control ,10,20,40 μmol/L deoxyschizandrin all decreased the relative protein expressions of p-Met ,p-PI3K,p-Akt,Bcl-2 and N-cadherin in cells significantly(P<0.05). CONCLUSIONS :Deoxyschizandrin can inhibit the proliferation ,migration and invasion of HONE- 1 cell via inhibiting the activation of Met/PI 3K/Akt signaling pathway.
10.Determination of Clopidogrel and Its Three Metabolites Concentrations in Human Plasma by LC-MS/MS
Zhirui LIU ; Pu YAO ; Bo YANG ; Yu WANG ; Wei FENG ; Fengjun SUN
China Pharmacy 2019;30(21):2946-2951
OBJECTIVE: To establish the method for simultaneous determination of clopidogrel (CLP), its intermediate metabolite (2-O-CLP), inactive metabolite (CLPCA) and active metabolite (CLPTM) in human plasma. METHODS: Totally 90 patients diagnosed as stroke were selected from the First Affiliated Hospital of Army Medical University. They were given one CLP tablet (75 mg/tablet) orally on an empty stomach in the morning. Blood samples were collected 2 h after taking the tablet. CLPTM- D was formed by derivation of CLPTM with 2-bromo-3’-methoxyacetophenone and extracted by precipitation of acetonitrile protein together with the other three substances to be measured. LC-MS/MS method was adopted. The determination was performed on Agilent poroshell 120 EC-C18 column with mobile phase consisted of acetonitrile (0.1% formic acid) and water (0.1% formic acid) (90 ∶ 10, V/V). The quantitation analysis was performed using multiple reaction monitoring at the specific ion transitions of m/z 308.1→198.1 (CLPCA), 322.3→212.0 (CLP), 338.3→155.0 (2-O-CLP), 504.4→354.1 (CLPTM-D) and 264.0→154.1 (ticlopidine, internal standard), respectively. RESULTS: The retention time of CLPCA, CLP, 2-O-CLP, CLPTM-D and internal standard were 2.01, 3.32, 2.83, 2.68, 1.87 min, respectively. The linear range of CLPCA, CLP, 2-O-CLP and CLPTM-D were 100-10 000, 0.2-20, 0.3-30, 0.5-50 ng/mL (all r≥0.999 5). The intra-day and inter-day RSD were all less than 9.5% (n=5). Accuracy ranged from 93.5%-98.9% (n=5), and extraction recovery was from 85.4% to 95.9% (n=5). The matrix effect ranged from 2.7%-6.2% (n=5). In stability tests (storing at -80 ℃ for 3 months, 3 freeze-thaw cycles, storing at 4 ℃ for 8 h), RE of CLP, CLPCA and CLPTM-D were all lower than 10.0% (n=5). CONCLUSIONS: Established LC-MS/MS method has the advantages of high specificity, accuracy and reliability, and can be used to detect the concentration of CLP and its three metabolites in human plasma.

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