1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.
2.Effect of Maxing Loushi Decoction on Inflammatory Factors, Immune Function, and PD-1/PD-L1 Signaling Pathway in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm Turbidity Obstructing Lung Syndrome
Yuexin SHI ; Zhi YAO ; Jun YAN ; Caijun WU ; Li LI ; Yuanzhen JIAN ; Guangming ZHENG ; Yanchen CAO ; Haifeng GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):143-150
ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm turbidity obstructing lung syndrome, and to investigate its effects on inflammatory factors, immune function, and the programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. MethodsA randomized controlled study was conducted, enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital, Beijing University of Chinese Medicine, from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table, with 45 patients in each group. The control group received conventional Western medical treatment, while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy, COPD Assessment Test (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walk test (6MWT), serum inflammatory factors, T lymphocyte subsets, and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% (33/42) in the control group and 95.35% (41/43) in the observation group, with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant (χ2 = 5.136, P<0.05). After treatment, both groups showed significant reductions in CAT and mMRC scores (P<0.05, P<0.01) and significant increases in 6MWT compared to baseline (P<0.01). The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1(MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were significantly reduced in both groups (P<0.05, P<0.01), with greater reductions in the observation group (P<0.05, P<0.01). CD8+ levels were significantly reduced (P<0.01), while CD3+, CD4+, and CD4+/CD8+ levels were significantly increased in both groups after treatment (P<0.05, P<0.01), with more significant improvements observed in the observation group (P<0.05, P<0.01). Serum PD-1 levels were reduced (P<0.05, P<0.01), and PD-L1 levels were increased significantly in both groups after treatment (P<0.05, P<0.01), with more pronounced changes in the observation group (P<0.05). ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors, improving immune function, and regulating the PD-1/PD-L1 signaling pathway.
3.Effect of Maxing Loushi Decoction on Inflammatory Factors, Immune Function, and PD-1/PD-L1 Signaling Pathway in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm Turbidity Obstructing Lung Syndrome
Yuexin SHI ; Zhi YAO ; Jun YAN ; Caijun WU ; Li LI ; Yuanzhen JIAN ; Guangming ZHENG ; Yanchen CAO ; Haifeng GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):143-150
ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm turbidity obstructing lung syndrome, and to investigate its effects on inflammatory factors, immune function, and the programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. MethodsA randomized controlled study was conducted, enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital, Beijing University of Chinese Medicine, from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table, with 45 patients in each group. The control group received conventional Western medical treatment, while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy, COPD Assessment Test (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walk test (6MWT), serum inflammatory factors, T lymphocyte subsets, and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% (33/42) in the control group and 95.35% (41/43) in the observation group, with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant (χ2 = 5.136, P<0.05). After treatment, both groups showed significant reductions in CAT and mMRC scores (P<0.05, P<0.01) and significant increases in 6MWT compared to baseline (P<0.01). The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1(MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were significantly reduced in both groups (P<0.05, P<0.01), with greater reductions in the observation group (P<0.05, P<0.01). CD8+ levels were significantly reduced (P<0.01), while CD3+, CD4+, and CD4+/CD8+ levels were significantly increased in both groups after treatment (P<0.05, P<0.01), with more significant improvements observed in the observation group (P<0.05, P<0.01). Serum PD-1 levels were reduced (P<0.05, P<0.01), and PD-L1 levels were increased significantly in both groups after treatment (P<0.05, P<0.01), with more pronounced changes in the observation group (P<0.05). ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors, improving immune function, and regulating the PD-1/PD-L1 signaling pathway.
4.Evaluation of nutritional value of three kinds of medicinal snakes based on content of 15 amino acids.
Xi WANG ; Ye-Yuan LIN ; Wen-Ting ZHONG ; Zhi-Guo MA ; Meng-Hua WU ; Hui CAO ; Ying ZHANG
China Journal of Chinese Materia Medica 2025;50(9):2411-2421
A high-performance liquid chromatography method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was developed to determine the content of 15 amino acids in the medicinal snakes Bungarus Parvus, Agkistrodon, and Zaocys. The results showed that the total amino acid(TAA) content ranged from 277.13 to 515.05 mg·g~(-1), with the top four amino acids in all three species being glutamic acid(Glu), glycine(Gly), aspartic acid(Asp), and lysine(Lys). The essential amino acid(EAA) content ranged from 74.56 to 203.94 mg·g~(-1), with Agkistrodon exhibiting the highest content. The non-essential amino acid(NEAA), semi-essential amino acid(semi-EAA), and medicinal amino acid(MAA) content ranged from 189.06 to 318.23, 12.89 to 33.53, and 179.83 to 342.33 mg·g~(-1), respectively, with Zaocys having the highest content in these categories. Amino acid nutritional value was evaluated using the amino acid ratio(RAA), amino acid ratio coefficient(RCAA), and amino acid ratio coefficient score(SRCAA), and the results indicated that all three medicinal snakes possessed good nutritional value. The amino acid composition was similar across the species, though significant differences in content were observed. Based on these differences, an orthogonal partial least squares-discriminant analysis(OPLS-DA) model was established, which could clearly distinguish between the three medicinal snake species. The key differences in amino acid content included Gly, tyrosine(Tyr), Glu, and serine(Ser), which may be related to the observed clinical application differences among the species. Further research into the mechanisms of these differential amino acids is expected to provide more insights into the clinical application disparities of these three medicinal snake species.
Amino Acids/chemistry*
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Animals
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Nutritive Value
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Chromatography, High Pressure Liquid
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Snakes/classification*
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Bungarus
5.Textual study of Baihuasheshecao (Hedyotis diffusa).
Dong-Min JIANG ; Chu-Chu ZHONG ; Pang-Chui SHAW ; Bik-San LAU ; Tai-Wai LAU ; Guang-Hao XU ; Ying ZHANG ; Zhi-Guo MA ; Hui CAO ; Meng-Hua WU
China Journal of Chinese Materia Medica 2025;50(15):4386-4396
Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans
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China
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Drugs, Chinese Herbal/chemistry*
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Hedyotis/classification*
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Medicine, Chinese Traditional/history*
6.Application of Assessment Scales in Palliative Care for Glioma: A Systematic Review.
Zhi-Yuan XIAO ; Tian-Rui YANG ; Ya-Ning CAO ; Wen-Lin CHEN ; Jun-Lin LI ; Ting-Yu LIANG ; Ya-Ning WANG ; Yue-Kun WANG ; Xiao-Peng GUO ; Yi ZHANG ; Yu WANG ; Xiao-Hong NING ; Wen-Bin MA
Chinese Medical Sciences Journal 2025;40(3):211-218
BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans
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Glioma/psychology*
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Palliative Care/methods*
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Quality of Life
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Psychometrics
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Brain Neoplasms/psychology*
7.A novel loop-structure-based bispecific CAR that targets CD19 and CD22 with enhanced therapeutic efficacy against B-cell malignancies.
Lijun ZHAO ; Shuhong LI ; Xiaoyi WEI ; Xuexiu QI ; Qiaoru GUO ; Licai SHI ; Ji-Shuai ZHANG ; Jun LI ; Ze-Lin LIU ; Zhi GUO ; Hongyu ZHANG ; Jia FENG ; Yuanyuan SHI ; Suping ZHANG ; Yu J CAO
Protein & Cell 2025;16(3):227-231
8.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
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Body Mass Index
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China/epidemiology*
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Male
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Female
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Middle Aged
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Prospective Studies
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Rural Population/statistics & numerical data*
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Aged
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Follow-Up Studies
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Adult
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Mortality
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Cause of Death
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Obesity/mortality*
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Overweight/mortality*
9.TRACKING EVALUATION ON THE IMPLEMENTATION OF"DIAGNOSIS OF ASCARIASIS"(WS/T 565-2017)IN ANHUI AND SICHUAN PROVINCES
Wei JIN ; Dao-Hua LIU ; Yang LIU ; Xiao-Hong WU ; Cheng-Hang YU ; Bin ZHENG ; Guang-Ming ZHANG ; Zhi-Guo CAO
Acta Parasitologica et Medica Entomologica Sinica 2025;32(2):73-77,111
Objective To understand the implementation status of"Diagnosis of Ascariasis"(WS/T 565-2017)and provide a scientific basis for promoting,revising,and improving the Standard.Methods Using the convenient sampling method,the investigation targeted professional and technical personnel at the provincial,city,county,and township levels engaged in parasitic disease prevention,control,or diagnosis and treatment in Anhui and Sichuan provinces.No less than 150 individuals were included in each province.The implementation survey of Diagnosis of Ascariasis(WS/T 565-2017)was conducted by the subjects completing a questionnaire by themselves.Results The response rate to the questionnaire was 91.90%(386/420).The awareness and utilization rates of the Standard were 81.87%and 49.22%,respectively and both increased with age(χ2 trend=7.977 and 19.016,respectively,P<0.01).Respondents with college degrees(90.72%)had a higher awareness rate(χ2=8.619,P<0.05).In terms of utilization rate,males(58.38%),those with college degrees(67.01%),staff members of provincial-level units(77.78%),and personnel in medical institutions(71.43%)had higher utilization rates(χ2=13.486,17.166,8.426,and 5.956,respectively,all P<0.05).The survey indicated that 57.77%of the work units of respondents have conducted promotional activities,and 53.89%of the work units of respondents have sent personnel to participate in training.Moreover,this proportion tended to increase as the unit level decreased(χ2 trend=9.403 and 14.729,P<0.01).The level of participation in publicity and training by medical institutions(89.29%)was significantly higher than that of disease control institutions(55.31%and 51.12%,respectively,χ2=12.290 and 15.225,P<0.01).Furthermore,training participation is a crucial factor in enhancing awareness rates.A total of 368 respondents(95.34%)reported that their work units have conducted testing for ascariasis.Additionally,378 individuals(97.92%)believe that the Standard is"applicable"or"basically applicable,"while 369(95.60%)felt that no revisions were needed.Conclusions The results indicated that"Diagnosis of Ascariasis"(WS/T 565-2017)remains applicable to the diagnostic needs of ascariasis and it is recommended to strengthen its promotion and implementation.
10.PRELIMINARY INVESTIGATION OF EHRLICHIA AND NEOEHRLICHIA IN RODENTS AT THE IMPORTANT PORTS ALONG THE"BELT AND ROAD"
Xiao-Long ZHANG ; Jia XU ; Shi-Liang MA ; Pi-Zheng WANG ; Juan PAN ; Jia-Yuan CAO ; Zhi-Wen SUN ; Hui-Lin GUO ; Li-Li XIAO
Acta Parasitologica et Medica Entomologica Sinica 2025;32(3):160-166
Objective This study aimed to investigate natural infection of rodents with Ehrlichia and Neoehrlichia at major Chinese land-border ports along the"Belt and Road".Methods In 2022,rodents were monitored in 10 ports in northern and southern China and identified based on diagnostic morphological characteristics.The 16S rRNA genes of Ehrlichia and Neoehrlichia were detected by PCR using universal primers from rodent samples and phylogenetic analysis was performed based on the sequences of the detected positive pathogens.Results A total of 356 rodents were sampled,including 2 orders,5 families,15 genera,and 20 species.Predominantly,73,61,56,and 58 were Meriones unguiculatus(20.51%),Rattus norvegicus(17.13%),Apodemus agrarius(15.73%),and Microtus gregalis(16.29%).Only one Microtus fortis from Suifenghe Port was infected with Ehrlichia sp.Moreover,12 rodents were infected with Neoehrlichia spp.(overall positivity rate:3.37%).Conclusions Natural infections with Ehrlichia spp.and Neoehrlichia spp.were demonstrated in rodents at important Chinese land-border ports.The positivity rate of Neoehrlichia spp.was high in some ports,indicating that surveillance for ticks and their prevention and control measures should be intensified in these regions.

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