1.Mycobacterium tuberculosis Rv3641c inhibits macrophage type Ⅰ interferon responses and promotes intracellular survival in macrophages
Wen JIN ; Min GENG ; Su-jie HU ; Xin-yang ZHANG ; Wen-qin LI ; Cheng-kun ZHENG ; Xin-an JIAO ; Xiang CHEN ; Zheng-zhong XU
Chinese Journal of Zoonoses 2025;41(4):385-391
This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.
2.Mycobacterium tuberculosis Rv3641c inhibits macrophage type Ⅰ interferon responses and promotes intracellular survival in macrophages
Wen JIN ; Min GENG ; Su-jie HU ; Xin-yang ZHANG ; Wen-qin LI ; Cheng-kun ZHENG ; Xin-an JIAO ; Xiang CHEN ; Zheng-zhong XU
Chinese Journal of Zoonoses 2025;41(4):385-391
This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.
3.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
4.In vitro activity of β-lactamase inhibitors combined with different β-lac-tam antibiotics against multidrug-resistant Mycobacterium tuberculosis clinical strains
Jie SHI ; Dan-Wei ZHENG ; Ji-Ying XU ; Xiao-Guang MA ; Ru-Yue SU ; Yan-Kun ZHU ; Shao-Hua WANG ; Wen-Jing CHANG ; Ding-Yong SUN
Chinese Journal of Infection Control 2024;23(9):1091-1097
Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33%(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.
5.Clinical observation of different intramedullary fixation methods for the treatment of intertrochanteric fracture
Li-Kun JIN ; Ye LI ; Jie ZHANG ; Yan-Xu DONG ; Yue-Feng QI
China Journal of Orthopaedics and Traumatology 2024;37(3):293-299
Objective To explore clinical efficacy of proximal femoral nail anti-rotation(PFNA),InterTan and proximal femoral bionic intramedullary nail(PFBN)in treating femoral intertrochanteric fracture.Methods Clinical data of 120 patients with intertrochanteric fracture who were underwent closed reduction intramedullary nail-internal fixation from January 2020 to January 2021 were retrospectively analyzed.According to methods of internal fixation,patients were divided into 3 groups.There were 25 patients in PFBN group,including 16 females and 9 males,aged from 69 to 79 years old with an average of(73.67±5.16)years old.There were 55 patients in PFNA group,including 38 females and 17 males,aged from 68 to 80 years old with an average of(74.23±5.57)years old.There were 40 patients in InterTan group,including 26 females and 14 males,aged from 68 to 79 years old with an average of(73.45±5.34)years old.Operative time,intraoperative blood loss,incision length,hospital stay,weight-bearing time,fracture healing time and complications among 3 groups were compared,and clinical effect was evaluated by Harris score of hip function before operation,1,6 and 12 months after opertaion,respectively.Results Patients among 3 groups were successfully completed operation and were followed up for more than 12 months.There were no significant difference in hospital stay,operative time,intraoperative blood loss and incision length among 3 groups(P>0.05).Weight bearing time of PFBN group(7.98±1.34)d and InterTan group(8.22±0.46)d were earlier than that of PFNA group(10.27±0.66)d(P<0.01).Fracture healing time of PFBN group(10.14±2.33)weeks and InterTan group(11.87±2.48)weeks were earlier than that of PFNA group(13.68±2.36)weeks(P<0.01).One month after operation,Harris score in PFBN group(70.52±5.34)and InterTan group(69.81±6.17)was higher than that of PFNA group(51.46±5.36),and there was no signifi-cant difference between PFBN group and InterTan group(f>0.05).There were no significant difference in Harris scores among 3 groups before operation,6 and 12 months after opertaion(P>0.05).Cases of complication of InterTan group and PFNA group were lower than that of PFNA group(P<0.05).Conclusion PFBN and InterTan for the treatment of intertrochanteric fracture have advantages of faster fracture healing,earlier weight-bearing time and fewer postoperative complications than traditional PFNA,but three operations could achieve higher effective rates without significant difference in long-term results.
6.Curative effect of repairing ankle joint fracture combined with deltoid ligament injury with suture anchor
Zhi-Kun WEI ; Fei SHAO ; Xu-Dong WANG ; Jin-Jie YANG ; Xiao-Bo FAN
Journal of Regional Anatomy and Operative Surgery 2024;33(8):713-717
Objective To investigate the curative effect of suture anchor(SA)repair combined with open reduction and internal fixation(ORIF)on patients with ankle joint fracture(AF)combined with deltoid ligament injury(DLI).Methods A total of 138 patients with AF combined with DLI admitted to our hospital from January 2020 to September 2022 were selected and divided into the control group(69 cases)and the observation group(69 cases)according to the random number table method.Patients in the control group were treated with ORIF,while patients in the observation group were treated with SA repair on the basis of the control group.The clinical efficacy,American Orthopedic Foot and Ankle Society(AOFAS)score,visual analogue scale(VAS)score,talus inclination angle,medial malleolar space of affected side,bone metabolic indexes[serum bone gla protein(BGP),β-collagen degradation product(β-CTX)]levels and the incidence of complications before and 3 months after treatment were compared between the two groups.Results The total effective rate in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Compared with before treatment,the talus inclination angle,medial malleolar space of affected side,VAS score,β-CTX level 3 months after treatment of patients in the two groups were reduced,while the AOFAS score and BGP level were increased,and the differences were statistically significant(P<0.05).After treatment,the AOFAS score and BGP level in the observation group were higher than those in the control group,while the talus inclination angle and medial malleolar space of affected side were smaller than those in the control group,and the VAS score and β-CTX level were lower than those in the control group,with statistically significant differences(P<0.05).The total incidence of complications in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion SA repair has a definite therapeutic effect on AF combined with DLI,which can improve patients' symptoms and promote the recovery of ankle joint function and bone metabolism.
7.Newborn screening, clinical features and genetic analysis for Citrin deficiency in Henan province
Xinyun ZHU ; Yizhuo XU ; Jie ZHANG ; Xiaole LI ; Jingwen HE ; Chenlu JIA ; Shubo LYU ; Suna LIU ; Yanbo GAO ; Kun MA ; Yunjia OUYANG ; Yihui REN ; Dehua ZHAO
Chinese Journal of Medical Genetics 2024;41(4):461-466
Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.
8.Impact of different reconstruction algorithms on PET image quality and diagnostic efficiency in patients with temporal lobe epilepsy
Kun SHANG ; Jie HU ; Zhenming WANG ; Jingjuan WANG ; Bixiao CUI ; Xiaoyin XU ; Jie LU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):678-683
Objective:To evaluate the value of time-of-flight (TOF) combined with point spread function (PSF) reconstruction for the improvement of brain PET images and lesion localization in patients with temporal lobe epilepsy (TLE).Methods:A retrospective collection of brain 18F-FDG PET imaging data of 52 hospitalized patients with TLE (30 males, 22 females, age: (26.7±7.1) years) and 26 healthy volunteers (14 males, 12 females, age: ( 31.7±6.8) years) from Xuanwu Hospital between 2017 and 2019 was conducted. Images were reconstructed and divided into 4 groups based on different algorithms: ordered subset expectation maximization (OSEM), OSEM+ TOF, OSEM+ PSF, and OSEM+ TOF+ PSF. The image quality, clarity, noise, and the clarity of lesion display of all subjects were visually analyzed using a four-point scale. The signal-to-noise ratio (SNR), contrast, and asymmetry index (AI) of the lesions were calculated. Differences in visual scores, SNR, contrast, and AI among the 4 groups were analyzed using one-way analysis of variance. The ROC curve was used to analyze the efficiency of PET images in localization of epileptogenic foci. Results:The visual score of OSEM+ TOF+ PSF group was the highest (4.0±0.0) among healthy volunteers; compared with OSEM group, OSEM+ TOF+ PSF group showed lower SNR (decreased by 46.6%; the lower the SNR value, the better the image quality) and contrast (increased by 29.8%). Visual assessment of PET images of patients with TLE showed that the scores of OSEM+ TOF+ PSF group , OSEM+ PSF group , OSEM+ TOF group and OSEM group were decreased in order (4.0±0.0 vs 3.4±0.5 vs 2.3±0.4 vs 1.0±0.0; F=884.0, P<0.001); SNRs of those 4 groups were increased in order ((5.2±2.4)% vs (6.2±2.4)% vs (7.9±2.6)% vs (8.9±3.5)%; F=18.82, P<0.001). The contrast and AI of the lesions in 4 groups were as follows: OSEM+ TOF+ PSF (contrast: 0.81±0.03; AI: 0.28±0.05) > OSEM+ TOF (0.74±0.05; 0.23±0.06) > OSEM+ PSF (0.72±0.06; 0.22±0.07) > OSEM (0.64±0.05; 0.19±0.06) ( F values: 107.10, 19.94, both P<0.001). MRI found unilateral hippocampal sclerosis in 32 patients, and the rest 20 patients with TLE were MRI-negative. ROC curve analysis showed that visual analysis and SUV ratio (SUVR) of lesion/contralateral ROI based on OSEM+ TOF+ PSF PET image could localize epileptogenic foci efficiently, with AUC of 0.874 in MRI-positive patients, and AUC of 0.932 in MRI-negative patients. Conclusions:The application of TOF and PSF significantly improves the quality of PET images. The combined use of both techniques yields the best results and aids in the localization of epileptogenic foci in patients with TLE.
9.Clinical study of electroacupuncture combined with exercise therapy in improving the balance function of patients with knee osteoarthritis
Kun XUE ; Ji WU ; Jie BAO ; Haiyin ZHAO ; Yun ZHAO ; Yusun LU ; Qiong XU ; Chunshui HUANG ; Xiehe KONG
Journal of Acupuncture and Tuina Science 2024;22(1):32-40
Objective:To observe the clinical effect of electroacupuncture(EA)combined with exercise therapy on balance function in patients with knee osteoarthritis(KOA). Methods:Seventy patients with KOA were randomly divided into a treatment group and a control group,with 35 cases in each group.The treatment group was treated with EA combined with exercise therapy.EA was applied to Dubi(ST35),Neixiyan(EX-LE4),Xuehai(SP10),Liangqiu(ST34),Yanglingquan(GB34),and Zusanli(ST 36).Exercise therapy(muscle strength training and knee mobility training)was applied after EA.The control group only received the same exercise therapy as the treatment group.The two groups were treated with the same course of treatment,3 times a week for 4 consecutive weeks,12 times in total,and followed up for 1 month.The Pro-Kin254P balance test system was used to measure the balance function parameters at 4 time points,including before treatment,after 1 session of treatment,after 12 sessions of treatment,and at 1-month follow-up after treatment.The visual analog scale(VAS)and the Western Ontario and McMaster Universities osteoarthritis index(WOMAC)scores were recorded. Results:The markedly effective rate and total effective rate in the treatment group were higher than those in the control group(P<0.01).The Romberg area,Romberg length,and VAS scores of the two groups decreased significantly after 1 session of treatment,12 sessions of treatment,and 1 month after treatment,and the differences between different time points in the same group were statistically significant(P<0.01).There were significant differences between the two groups at the same time point(P<0.05).The total WOMAC scores of the two groups after 1 session of treatment,12 sessions of treatment,and 1 month after treatment decreased significantly,and there were significant differences between different time points in the same group(P<0.05),but there was no significant difference between the two groups at the same time point(P>0.05). Conclusion:EA combined with exercise therapy or exercise therapy alone can enhance the balance function,relieve joint pain,and improve joint function in patients with KOA.EA combined with exercise therapy is superior to exercise therapy alone in improving balance function and pain,but the two treatment protocols have similar effects in improving joint function.
10.High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China
Jing XU ; Qiang WANG ; Kun YANG ; Liyong WEN ; Tianping WANG ; Dandan LIN ; Jianbing LIU ; Jie ZHOU ; Yang LIU ; Yi DONG ; Chunli CAO ; Shizhu LI ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(1):1-6
The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

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