Evaluating the effectiveness of a new student-centred laboratory training strategy in clinical biochemistry teaching.

BACKGROUND: The error-proneness in the preanalytical and postanalytical stages is higher than that in the analytical stage of the total testing process. However, preanalytical and postanalytical quality management has not received enough attention in medical laboratory education and tests in clinical biochemistry courses. METHODS/APPROACH: Clinical biochemistry teaching program aim to improve students' awareness and ability of quality management according to international organization for standardization 15,189 requirements. We designed a student-centred laboratory training program, according to case-based learning that included 4 stages: "establish an overall testing process based on the patient's clinical indicator, clarify principles, improve operational skills, and review process and continuous improvement". The program was implemented in our college during the winter semesters of 2019 and 2020. A total of 185 undergraduate students majoring in medical laboratory science participated in the program as a test group, and the other 172 students were set up as the control group and adopted the conventional method. The participants were asked to finish an online survey to evaluate the class at the end. RESULTS/OUTCOMES: The test group had significantly better examination scores not only in experimental operational skills (89.27 ± 7.16 vs. 77.51 ± 4.72, p < 0.05 in 2019 grade, 90.31 ± 5.35 vs. 72.87 ± 8.41 in 2020 grade) but also in total examination (83.47 ± 6.16 vs. 68.90 ± 5.86 in 2019 grade, 82.42 ± 5.72 vs. 69.55 ± 7.54 in 2020 grade) than the control group. The results of the questionnaire survey revealed that the students in the test group better achieved classroom goals than those in the control group (all p < 0.05). CONCLUSIONS: The new student-centred laboratory training program based on case-based learning in clinical biochemistry is an effective and acceptable strategy compared with the conventional training program.

A phase Ib study of camrelizumab in combination with apatinib and fuzuloparib in patients with recurrent or metastatic triple-negative breast cancer.

BACKGROUND: Strategies to improve activity of immune checkpoint inhibitors for triple-negative breast cancer (TNBC) are needed. Preclinical studies showed that antiangiogenic agents and poly (ADP-ribose) polymerase (PARP) inhibitors might sensitize tumors to immunotherapy. Here, we investigated the tolerability, safety, and preliminary antitumor activity of camrelizumab, an anti-PD-1 antibody, in combination with apatinib, a vascular endothelial growth factor receptor-2 inhibitor, and fuzuloparib, a PARP inhibitor, in patients with recurrent or metastatic TNBC. METHODS: This phase Ib study included a dose-finding part and a dose-expansion part. In the dose-finding part, a 3 + 3 dose escalation scheme was introduced. Patients were given camrelizumab (200 mg every 2 weeks) plus apatinib (375 mg or 500 mg once daily) and fuzuloparib (starting dose 100 mg twice daily) every 28-day cycle. After evaluation of the tolerability and safety of the dosing regimens, a clinical recommended dose was determined for the dose-expansion part. The primary endpoint was dose-limiting toxicity (DLT). RESULTS: A total of 32 patients were enrolled. Three patients received camrelizumab 200 mg + apatinib 375 mg + fuzuloparib 100 mg, and 29 received camrelizumab 200 mg + apatinib 500 mg + fuzuloparib 100 mg (clinical recommended dose). No DLTs were observed in either group. The most common grade ≥ 3 treatment-related adverse events were decreased white blood cell count (20.7%), hypertension (13.8%), decreased neutrophil count (10.3%), and increased aspartate aminotransferase (10.3%). Two patients discontinued study treatment due to immune-mediated hepatitis (n = 1) and anemia, decreased platelet count, decreased white blood cell count, increased alanine aminotransferase, increased aspartate aminotransferase, and increased γ-glutamyltransferase (n = 1). One patient died of unknown cause. Two (6.9% [95% CI, 0.9-22.8]) of 29 patients with camrelizumab 200 mg + apatinib 500 mg + fuzuloparib 100 mg had objective response. The disease control rate was 62.1% (95% CI, 42.3-79.3). The median progression-free survival was 5.2 months (95% CI, 3.6-7.3), and the 12-month overall survival rate was 64.2% (95% CI, 19.0-88.8). CONCLUSIONS: Combination of camrelizumab plus apatinib and fuzuloparib showed manageable safety profile and preliminary antitumor activity in patients with recurrent or metastatic TNBC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945604 (May 10, 2019).

Serological and molecular characteristics of pathogenic Leptospira in rodent populations in Fujian Province, China, 2018-2020.

BACKGROUND: Leptospirosis is a significant emerging infectious disease worldwide. Rodents are considered to be the most critical hosts of Leptospira spp. Fujian Province is a region highly endemic for leptospirosis in China. However, the genetic diversity of leptospires circulating among rodents in Fujian is limited. RESULTS: The carrier status of rodents for Leptospira spp. was investigated by culture and serological detection in Fujian during 2018-2020. A total of 710 rodents, including 11 species, were trapped, with Rattus losea being the dominant trapped species (50.56%). Fourteen pathogenic Leptospira strains were obtained. Seven L. borgpetersenii serogroup Javanica strains belonging to ST143, 4 L. interrogans serogroup Icterohaemorrhagiae strains belonging to ST1 and ST17, 2 L. interrogans serogroup Bataviae strains belonging to ST96 and ST333, and 1 L. interrogans serogroup Pyrogenes strains belonging to ST332 were identified using 16S rDNA gene sequencing, microscopic agglutination test (MAT) and Multilocus sequence typing (MLST). L. borgpetersenii serogroup Javanica belonging to ST143 was the dominant type (50.00%). A total of 387 rodent serum samples were tested by MAT. Serum were considered positive for seroreactivity at a titer ≥ 1:160 against at least one serovar. A total of 90 (23.26%) serum samples tested positive, and four serogroups were identified, with Javanica being the dominant serogroup (87.78%), which was similar to the dominant serogroup isolated from rodents. This study demonstrates a high prevalence of leptospirosis in rodents and public health education among high-risk workers is highly recommended. CONCLUSIONS: R. losea was the dominant trapped rodent, and L. borgpetersenii serogroup Javanica ST143 was widely distributed among rodents in Fujian from 2018 to 2020. Despite the low number of isolates obtained from rodents, this study suggests that continuous epidemiological surveillance of the aetiological characteristics of pathogenic Leptospira in wild animal reservoirs may help reduce the possible risk of disease transmission.

A Bayesian adaptive phase I/II platform trial design for pediatric immunotherapy trials.

Immunotherapy is the most promising new cancer treatment for various pediatric tumors and has resulted in an unprecedented surge in the number of novel immunotherapeutic treatments that need to be evaluated in clinical trials. Most phase I/II trial designs have been developed for evaluating only one candidate treatment at a time, and are thus not optimal for this task. To address these issues, we propose a Bayesian phase I/II platform trial design, which accounts for the unique features of immunotherapy, thereby allowing investigators to continuously screen a large number of immunotherapeutic treatments in an efficient and seamless manner. The elicited numerical utility is adopted to account for the risk-benefit trade-off and to quantify the desirability of the dose. During the trial, inefficacious or overly toxic treatments are adaptively dropped from the trial and the promising treatments are graduated from the trial to the next stage of development. Once an experimental treatment is dropped or graduated, the next available new treatment can be immediately added and tested. Extensive simulation studies have demonstrated the desirable operating characteristics of the proposed design.

An adaptive gBOIN design with shrinkage boundaries for phase I dose-finding trials.

BACKGROUND: With the emergence of molecularly targeted agents and immunotherapies, the landscape of phase I trials in oncology has been changed. Though these new therapeutic agents are very likely induce multiple low- or moderate-grade toxicities instead of DLT, most of the existing phase I trial designs account for the binary toxicity outcomes. Motivated by a pediatric phase I trial of solid tumor with a continuous outcome, we propose an adaptive generalized Bayesian optimal interval design with shrinkage boundaries, gBOINS, which can account for continuous, toxicity grades endpoints and regard the conventional binary endpoint as a special case. RESULT: The proposed gBOINS design enjoys convergence properties, e.g., the induced interval shrinks to the toxicity target and the recommended dose converges to the true maximum tolerated dose with increased sample size. CONCLUSION: The proposed gBOINS design is transparent and simple to implement. We show that the gBOINS design has the desirable finite property of coherence and large-sample property of consistency. Numerical studies show that the proposed gBOINS design yields good performance and is comparable with or superior to the competing design.

Enhancing KCNQ Channel Activity Improves Neurobehavioral Recovery after Spinal Cord Injury.

Spinal cord injury (SCI) usually leads to acute neuronal death and delayed secondary degeneration, resulting in sensory dysfunction, paralysis, and chronic pain. Excessive excitation is one of the critical factors leading to secondary neural damage initiated by various insults. KCNQ/Kv7 channels are highly expressed in spinal neurons and axons and play an important role in controlling their excitability. Enhancing KCNQ channel activity by using its specific opener retigabine could thus be a plausible treatment strategy to reduce the pathology after SCI. We produced contusive SCI at T10 in adult male rats, which then received 10 consecutive days' treatment with retigabine or vehicle starting 3 hours or 3 days after contusion. Two different concentrations and two different delivery methods were applied. Delivery of retigabine via Alzet osmotic pumps, but not intraperitoneal injections 3 hours after contusion, promoted recovery of locomotor function. Remarkably, retigabine delivery in both methods significantly attenuated the development of mechanical stimuli-induced hyperreflexia and spontaneous pain; however, no significant difference in the thermal threshold was observed. Although retigabine delivered 3 days after contusion significantly attenuated the development of mechanical hypersensitivity and spontaneous pain, the locomotor function is not improved by the delayed treatments. Finally, we found that early application of retigabine attenuates the inflammatory activity in the spinal cord and increases the survival of white matter after SCI. Our results suggest that decreasing neuronal excitability by targeting KCNQ/Kv7 channels at acute stage aids the recovery of locomotor function and attenuates the development of neuropathic pain after SCI. SIGNIFICANCE STATEMENT: Several pharmacological interventions have been proposed for spinal cord injury (SCI) treatment, but none have been shown to be both effective and safe in clinical trials. Necrotic neuronal death and chronic pain are often the cost of pathological neural excitation after SCI. We show that early, brief application of retigabine could aid locomotor and sensory neurobehavioral recovery after SCI, supporting the use of this drug in the clinic to promote motor and sensory function in patients with SCI.

[Investigation and genetic identification on Babesia infection in rodents in some areas of Fujian Province].

Objective: To explore the status of Babesia infection in rodents and the genetic characteristics of Babesia spp. in Fujian Province. Methods: Rodents were captured by the night trapping method in Shaowu, Qingliu, Shunchang, Yong'an, Changle and Youxi during 2014-2015. The rodent species was identified, and information on the time and place of capture, species and sex of rodents was recorded. Blood samples was collected, in which the fragment of 18S rRNA gene of Babesia spp. was amplified by PCR. The PCR products were sequenced and the phylogenetic tree was constructed for homology analysis. Data on positive rate were analyzed with Chi-square or Fisher exact test. Results: Two hundred and nine rats were captured, comprising of 71 domestic and 138 wild rats. The overall positive rate was 9.6%(20/209). The positive rate in domestic rats was 2.8%(2/71), including one Rattus norvebicus and one Rattus flavipectus. The positive rate in wild rats was 13.0%(18/138), including 13 Bandicota indica, one Rattus losea, 2 Rattus confucianus and 2 Rattus fulvescens. The positive rate was significantly higher in wild rats than in domestic rats (P < 0.05). The Youxi region had the highest positive rate(14.9%,13/87), followed by Yong'an(13.6%, 3/22), and no positive rat was found in Qingliu. The positive rate in the male rats was 7.9%(9/114), and that in the females was 11.6%(11/95). The positive rate was highest in adult rats (10.4%,18/173), followed by young ones (6.3%,2/32). No positive rat was found in old rats. There was no significant difference in positive rate among different regions, between male and female rats, or among different ages (P > 0.05). The sequences of PCR products had a 100% homology. The BLAST results revealed the species to be Babesia microti. The phylogenetic tree showed that the sample sequence was the most homologous with Babesia microti from Zhejiang Province(GenBank Accession No: JQ609305). Conclusion: There occurs Babesia microti infection in rats in part areas of Fujian Province. The positive rate was higher in wild rats than in domestic rats.

Factors associated with menopausal symptoms among middle-aged registered nurses in Beijing.

OBJECTIVE: To determine factors related to menopause symptoms among middle-aged registered nurses in Beijing. METHODS: Self-administered questionnaires that included closed-ended questions on many factors possibly related to menopausal symptoms were distributed to 2100 registered nurses aged 40-55 at 20 hospitals in Beijing, China. RESULTS: Menopausal status was most associated with menopausal symptoms (p < 0.01), including hot flashes and sweating, paresthesiae, insomnia, arthralgia/myalgia, palpitations, skin formication and an unsatisfactory sexual life. The odds ratios (ORs) were highest for hot flashes and sweating. Upsetting events in the past year and being pessimistic were significantly inversely correlated with almost all the symptoms analyzed. Hot flashes and sweating (p < 0.01), paresthesiae (p < 0.01), unsatisfactory sexual life (p < 0.01), irritability (p < 0.05), depression or suspicion (p < 0.05) and dizziness (p < 0.05) were negatively correlated with the frequency of sexual activity. CONCLUSION: Many factors may influence symptoms of the menopause. We found that menopausal status was most strongly associated with most menopausal symptoms, especially hot flashes and sweating. Psychosocial factors also played an important role. A higher frequency of sexual activity negatively correlated with most menopausal symptoms.

Two new flavonoids from the roots of Scutellaria baicalensis.

One new flavone, 5,7-dihydroxy-8,2',3',6'-tetramethoxyflavone (1), and one new flavonol, 5,7,6'-trihydroxy-2'-methoxyflavonol (2), were isolated from the roots of Scutellaria baicalensis, and their structures were elucidated on the basis of extensive spectroscopic evidences, especially 1D and 2D NMR and HR-ESI-MS experiments. The structure features of these new compounds lie in the substitution at both C-2' and C-6' positions of B-ring by hydroxyl or methoxyl groups.

Changes of c-fos, malondialdehyde and lactate in brain tissue after global cerebral ischemia under different brain temperatures.

Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic (37-38°C) ischemia, mild hypothermic (31-32°C) ischemia, hyperthermic (41-42°C) ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20-min ischemia. The expression of c-fos protein and the levels of malondialdehyde (MDA) and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-fos protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion following 20-min ischemia as compared with the sham-operated group (P<0.01). The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group (P<0.01). It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.

Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury.

Traumatic spinal cord injury (SCI) results in immediate tissue necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progressive hemorrhagic necrosis (PHN) and excessive excitation are the main sources of secondary neural injury. Recent approaches to attenuate PHN by glibenclamide can improve locomotor function after SCI. However, use of glibenclamide can exacerbate development of SCI-induced chronic pain by inhibiting KATP channels to increase neuronal excitation and glial activation. In this study, we explored a treatment strategy involving administration of glibenclamide, which suppresses PHN, and diazoxide, which protects against neuronal excitation and inflammation, at different time intervals following spinal cord contusion. Our goal was to determine whether this combined approach enhances both sensory and motor function. Contusive SCI was induced at spinal segment T10 in adult rats. We found that KATP channels opener, diazoxide, decreased the hyperexcitability of primary sensory neurons after SCI by electrophysiology. Timed application of glibenclamide and diazoxide following contusion significantly improved locomotor function and mitigated development of SCI-induced chronic pain, as shown by behavioral evidence. Finally, we found that timed application of glibenclamide and diazoxide attenuates the inflammatory activity in the spinal cord and increases the survival of spinal matters following SCI. These preclinical studies introduce a promising potential treatment strategy to address SCI-induced dysfunction.

Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study.

Background: Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC). Objectives: To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC. Design: A multicenter, open-label, phase Ib trial. Methods: Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1-2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3-5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety. Results: A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%-93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%-87.5% for lower doses; grade 4, 46.7% and 4.2%-20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%-54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5-82.6) and patients progressing after ET (53.3%; 95% CI 26.6-78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9-46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9-24.1) with fulvestrant. Conclusion: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. Trial registration: ClinicalTrials.gov identifier: NCT03481998.

Advancements in autologous peripheral nerve transplantation care: a review of strategies and practices to facilitate recovery.

Autologous peripheral nerve transplantation, a pioneering technique in nerve injury treatment, has demonstrated remarkable progress. We examine recent nursing strategies and methodologies tailored to various anatomical sites, highlighting their role in postoperative recovery enhancement. Encompassing brachial plexus, upper limb, and lower limb nerve transplantation care, this discussion underscores the importance of personalized rehabilitation plans, interdisciplinary collaboration, and innovative approaches like nerve electrical stimulation and nerve growth factor therapy. Moreover, the exploration extends to effective complication management and prevention strategies, encompassing infection control and pain management. Ultimately, the review concludes by emphasizing the advances achieved in autologous peripheral nerve transplantation care, showcasing the potential to optimize postoperative recovery through tailored and advanced practices.

Corrigendum: Case report: Potential predictive value of MMR/MSI status and PD-1 expression in immunotherapy for urothelial carcinoma.

[This corrects the article DOI: 10.3389/pore.2022.1610638.].

RNA m6A modification orchestrates the rhythm of immune cell development from hematopoietic stem cells to T and B cells.

RNA, one of the major building blocks of the cell, participates in many essential life processes. RNA stability is well-established to be closely related to various RNA modifications. To date, hundreds of different RNA modifications have been identified. N6-methyladenosine (m6A) is one of the most important RNA modifications in mammalian cells. An increasing body of evidence from recently published studies suggests that m6A modification is a novel immune system regulator of the generation and differentiation of hematopoietic stem cells (HSCs) and immune cells. In this review, we introduce the process and relevant regulatory mechanisms of m6A modification; summarize recent findings of m6A in controlling HSC generation and self-renewal, and the development and differentiation of T and B lymphocytes from HSCs; and discuss the potential mechanisms involved.

Paclitaxel Inhibits KCNQ Channels in Primary Sensory Neurons to Initiate the Development of Painful Peripheral Neuropathy.

Cancer patients undergoing paclitaxel infusion usually experience peripheral nerve degeneration and serious neuropathic pain termed paclitaxel-induced peripheral neuropathy (PIPN). However, alterations in the dose or treatment schedule for paclitaxel do not eliminate PIPN, and no therapies are available for PIPN, despite numerous studies to uncover the mechanisms underlying the development/maintenance of this condition. Therefore, we aimed to uncover a novel mechanism underlying the pathogenesis of PIPN. Clinical studies suggest that acute over excitation of primary sensory neurons is linked to the pathogenesis of PIPN. We found that paclitaxel-induced acute hyperexcitability of primary sensory neurons results from the paclitaxel-induced inhibition of KCNQ potassium channels (mainly KCNQ2), found abundantly in sensory neurons and axons. We found that repeated application of XE-991, a specific KCNQ channel blocker, induced PIPN-like alterations in rats, including mechanical hypersensitivity and degeneration of peripheral nerves, as detected by both morphological and behavioral assays. In contrast, genetic deletion of KCNQ2 from peripheral sensory neurons in mice significantly attenuated the development of paclitaxel-induced peripheral sensory fiber degeneration and chronic pain. These findings may lead to a better understanding of the causes of PIPN and provide an impetus for developing new classes of KCNQ activators for its therapeutic treatment.

Application of problem-based learning combined with a virtual simulation training platform in clinical biochemistry teaching during the COVID-19 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a great impact on the traditional teaching mode (Lecture-based Learning, LBL) and laboratory teaching. To address this challenge, the researchers conducted online Problem-based learning (PBL) teaching and virtual simulation laboratory teaching through DingTalk, and evaluated the effectiveness of this method in teaching clinical biochemistry. Methods: With the method of cluster sampling, the researchers randomly selected 60 students from two classes of the Class 2019 as the experimental group for this prospective experimental study. The theory class was taught online PBL through DingTalk, and experimental lectures were given by virtual simulation. After the experimental teaching, students were assessed for theory and operation. Self-administered questionnaires were administered through DingTalk. 65 students from our 2018 medical laboratory class were randomly selected as the control group, and offline LBL and traditional experimental teaching methods were used. Examination results were obtained through teaching portfolios. Results: The experimental group had significantly better examination scores in theoretical knowledge and experimental operational skills than the control group (87.45 ± 5.91 vs. 83.52 ± 9.94, P = 0.0095; 87.08 ± 12.42 vs. 80.18 ± 14.04, P = 0.0044). The results of the questionnaire survey revealed that the experimental group was more receptive to the DingTalk-PBL teaching method and virtual simulation laboratory teaching. Moreover, this hybrid teaching method was more effective in promoting basic knowledge understanding (95.0%, 57/60), facilitating the mastery of operational skills (93.3, 56/60), cultivating interest in learning (96.7%, 58/60), training clinical thinking (95.0%, 57/60), improving communication skills (95.0%, 57/60), and enhancing self-learning ability (91.7%, 55/60) and was more satisfying than traditional teaching method (all P < 0.05). Conclusion: The DingTalk-based PBL method combined with virtual simulation experiments was an effective and acceptable teaching strategy during the pandemic compared with the traditional teaching method.

Down-regulation of GAS5 has diagnostic value for tuberculosis and regulates the inflammatory response in mycobacterium tuberculosis infected THP-1 cells.

OBJECTIVE: This study aimed to investigate the expression of long non-coding RNA (lncRNA) growth arrest-special transcript 5 (GAS5) in the serum of tuberculosis (TB) patients and discuss the mechanism of GAS5 in TB by establishing an in-vitro TB cell model. METHODS: Serum expressions of GAS5 and miR-18a-5p were determined by quantitative real-time PCR (qRT-PCR). The effects of GAS5 on macrophage cell viability and the inflammatory response after MTB infection were assessed by CCK-8 and ELISA. Luciferase reporter gene assay was applied to delve into the potential target gene of GAS5. RESULTS: The expression of GAS5 in TB patients was down-regulated, while miR-18a-5p was up-regulated, and the serum inflammatory factors were negatively correlated with the expression level of GAS5. MTB infection induced significant upregulation on the cell viability and inflammatory response but the acceleration effect could be rescued by GAS5-overexpression. Meanwhile, miR-18a-5p was recognized as the target gene of GAS5. CONCLUSION: This study indicated that the expression level of GAS5 in the serum of TB patients was decreased, while in the cells infected with MTB, the down-regulated GAS5 might develop a role in facilitating the cell vitality and the inflammatory response by adsorbing miR-18a-5p in the form of molecular sponge.

Epidemiological characteristics and genetic diversity of Bartonella species in rodents from southeastern China.

Rodents are the primary hosts of Bartonella species and carry more than 22 Bartonella species. However, the information on epidemiological characteristics and genetic diversity of Bartonella species in rodents in southeastern China is limited. From 2015 to 2020, 1,137 rodents were captured. Bartonella-positive DNA was detected in 14.9% (169/1,137) of rodents by PCR for both the ssrA and gltA genes. A highest Bartonella prevalence was detected in Apodemus agrarius (33.5%) and lowest in B. indica (1.8%). The probability of Bartonella infection in summer (20.1%) was higher than in spring (14.6%; p = .011, OR = 1.756). Sequencing and phylogenetic analysis revealed that nine known Bartonella species were identified in rodents, including B. tribocorum, B. grahamii, B. rattimassiliensis, B. queenslandensis, B. elizabethae, B. phoceensis, B. coopersplainsensis, B. japonica and B. rochalimae. In our study, Bartonella species exhibited a strong association with their hosts. Zoonotic B. tribocorum, B. grahamii, B. elizabethae and B. rochalimae were found in synanthropic rodent species in southeastern China, which pose a potential threat to the public health. To prevent the spread of zoonotic Bartonella species to humans, preventive and control measures should be implemented, and more research is needed to confirm the pathogen's association with human disease.

Prevalence and phylogenetic analysis of Babesia parasites in reservoir host species in Fujian province, Southeast China.

Babesiosis is a tick-borne disease that mainly affects small mammals and has been reported in at least five provinces in China. However, the host range and geographical distribution of the parasite in Fujian province are unclear. Therefore, we investigated the prevalence and genetic characteristics of Babesia in Fujian province, Southeast China, between 2015 and 2020. Rodent blood samples were collected from 26 different surveillance sites across Fujian province. Genomic DNA was extracted to screen for Babesia infection using polymerase chain reaction based on 18S rRNA. DNA samples from 316 domestic goats, 85 water buffalo, 56 domestic dogs and 18 domestic pigs were examined. The prevalence of Babesia was statistically analysed using the Chi-square test or Fisher's exact test. Babesia infections were detected in 3.96% (43/1,087; 95%CI: 2.80%, 5.12%) of rodents and 1.26% (6/475; 95%CI: 0.26%, 2.26%) of other mammals. Multivariate logistic regression analysis revealed that irrigated cropland, shrubs and forests were risk factors for Babesia microti infections. The infection rates among domestic pigs, dogs and goats were 5.56%, 1.79% and 1.27%, respectively, with no infection found in water buffalo. The 18S rRNA gene sequencing revealed that rodents were infected with Babesia (sensu lato), whereas other mammals were infected with Babesia (sensu stricto). The geographical distribution and phylogenetic relationship of Babesia was determined in Southeast China. Mammals, particularly wild rodents, maybe the main natural hosts of Babesia in Fujian. Our findings provide a foundation for public health officials to develop prevention and control measures for Babesia.