DNA Reaction Circuits to Establish Designated Biological Functions in Multicellular Community.

In multicellular organisms, individual cells are coordinated through complex communication networks to accomplish various physiological tasks. Aiming to establish new biological functions in the multicellular community, we used DNA as the building block to develop a cascade of nongenetic reaction circuits to establish a dynamic cell-cell communication network. Utilizing membrane-anchored amphiphilic DNA tetrahedra (TDN) as the nanoscaffold, reaction circuits were incorporated into three unrelated cells in order to uniquely regulate their sense-and-response behaviors. As a proof-of-concept, this step enabled these cells to simulate significant biological events involved in T cell-mediated anticancer immunity. Such events included cancer-associated antigen recognition and the presentation of antigen-presenting cells (APCs), APC-facilitated T cell activation and dissociation, and T cell-mediated cancer targeting and killing. By combining the excellent programmability and molecular recognition ability of DNA, our cell-surface reaction circuits hold promise for mimicking and manipulating many biological processes.

Corrigendum: Therapeutic strategies targeting folate receptor α for ovarian cancer.

[This corrects the article DOI: 10.3389/fimmu.2023.1254532.].

Aptamer-Based Nongenetic Reprogramming of CARs Enables Flexible Modulation of T Cell-Mediated Tumor Immunotherapy.

Innovating the design of chimeric antigen receptors (CARs) beyond conventional structures would be necessary to address the challenges of efficacy, safety, and applicability in T cell-based cancer therapy, whereas excessive genetic modification might complicate CAR design and manufacturing, and increase gene editing risks. In this work, we used aptamers as the antigen-recognition unit to develop a nongenetic CAR engineering strategy for programming the antitumor activity and specificity of CAR T cells. Our results demonstrated that aptamer-functionalized CAR (Apt-CAR) T cells could be directly activated by recognizing target antigens on cancer cells, and then impart a cytotoxic effect for cancer elimination in vitro and in vivo. The designable antigen recognition capability of Apt-CAR T cells allows for easy modulation of their efficacy and specificity. Additionally, multiple features, e.g., tunable antigen-binding avidity and the tumor microenvironment responsiveness, could be readily integrated into Apt-CAR design without T cell re-engineering, offering a new paradigm for developing adaptable immunotherapeutics.

Identifying key risk factors for acute compartment syndrome in tibial diaphysis fracture patients.

Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p < 0.001, OR = 1.003), and white blood cell (WBC) count (p < 0.001, OR = 1.246). Interestingly, the study also found that certain factors, such as falls on the same level (p = 0.007, OR = 0.334) and cholinesterase (CHE) levels (p < 0.001, OR = 0.721), seem to provide a degree of protection against ACS. In order to better predict ACS, the ROC curve analysis was employed, which determined threshold values for LDH and WBC. The established cut-off points were set at 266.26 U/L for LDH and 11.7 × 109 cells per liter for WBC, respectively. Our research has successfully pinpointed gender, crush injuries, LDH levels, and white blood cell (WBC) count as crucial risk factors for the development of ACS in patients experiencing tibial diaphysis fractures. Furthermore, by establishing the cut-off values for LDH and WBC, we have facilitated a more personalized assessment of ACS risk, enabling clinical doctors to implement targeted early interventions and optimize patient outcomes.

The impacts of dietary sphingomyelin supplementation on metabolic parameters of healthy adults: a systematic review and meta-analysis of randomized controlled trials.

Background: Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome (MetS), while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate MetS. Therefore, we hypothesized that dietary SM supplementation is beneficial for human health. Aims: In order to examine the impacts of dietary SM on metabolic indexes in adults without MetS, we performed a meta-analysis to test our hypothesis. Methods: A comprehensive search was performed to retrieve randomized controlled trials that were conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. RevMan 5.4 and Stata 14.0 software were used for meta-analysis, a sensitivity analysis, the risk of bias, and the overall quality of the resulted evidence. Results: Eventually, 10 articles were included in this meta-analysis. Dietary SM supplementation did not affect the endline blood SM level. When compared to the control, SM supplementation reduced the blood total cholesterol level [MD: -12.97, 95% CI: (-14.57, -11.38), p < 0.00001], low-density lipoprotein cholesterol level [MD: -6.62, 95% CI: (-10.74, -2.49), p = 0.002], and diastolic blood pressure [MD: -3.31; 95% CI (-4.03, -2.58), p < 0.00001] in adults without MetS. The supplementation also increased high-density lipoprotein level [MD:1.41, 95% CI: (0.94, 1.88), p < 0.00001] and muscle fiber conduction velocity [MD: 95% 1.21 CI (0.53, 1.88), p = 0.0005]. The intake of SM had no effect on the blood phospholipids and lyso-phosphatidylcholine, but slightly decreased phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol concentrations. Dietary SM supplementation reduced insulin level [MD: -0.63; 95% CI (-0.96, -0.31), p = 0.0001] and HOMA-IR [MD: -0.23; 95% CI (-0.31, -0.16), p < 0.00001] without affecting blood levels of glucose and inflammatory cytokines. Conclusion: Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without MetS. More clinical trials and basic research are required. Systematic review registration: PROSPERO, identifier CRD42023438460.

A lightweight hybrid vision transformer network for radar-based human activity recognition.

Radar-based human activity recognition (HAR) offers a non-contact technique with privacy protection and lighting robustness for many advanced applications. Complex deep neural networks demonstrate significant performance advantages when classifying the radar micro-Doppler signals that have unique correspondences with human behavior. However, in embedded applications, the demand for lightweight and low latency poses challenges to the radar-based HAR network construction. In this paper, an efficient network based on a lightweight hybrid Vision Transformer (LH-ViT) is proposed to address the HAR accuracy and network lightweight simultaneously. This network combines the efficient convolution operations with the strength of the self-attention mechanism in ViT. Feature Pyramid architecture is applied for the multi-scale feature extraction for the micro-Doppler map. Feature enhancement is executed by the stacked Radar-ViT subsequently, in which the fold and unfold operations are added to lower the computational load of the attention mechanism. The convolution operator in the LH-ViT is replaced by the RES-SE block, an efficient structure that combines the residual learning framework with the Squeeze-and-Excitation network. Experiments based on two human activity datasets indicate our method's advantages in terms of expressiveness and computing efficiency over traditional methods.

Therapeutic strategies targeting folate receptor α for ovarian cancer.

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration.

LepR+ niche cell-derived AREG compromises hematopoietic stem cell maintenance under conditions of DNA repair deficiency and aging.

The cross talk between extrinsic niche-derived and intrinsic hematopoietic stem cell (HSC) factors controlling HSC maintenance remains elusive. Here, we demonstrated that amphiregulin (AREG) from bone marrow (BM) leptin receptor (LepR+) niche cells is an important factor that mediates the cross talk between the BM niche and HSCs in stem cell maintenance. Mice deficient of the DNA repair gene Brca2, specifically in LepR+ cells (LepR-Cre;Brca2fl/fl), exhibited increased frequencies of total and myeloid-biased HSCs. Furthermore, HSCs from LepR-Cre;Brca2fl/fl mice showed compromised repopulation, increased expansion of donor-derived, myeloid-biased HSCs, and increased myeloid output. Brca2-deficient BM LepR+ cells exhibited persistent DNA damage-inducible overproduction of AREG. Ex vivo treatment of wild-type HSCs or systemic treatment of C57BL/6 mice with recombinant AREG impaired repopulation, leading to HSC exhaustion. Conversely, inhibition of AREG by an anti-AREG-neutralizing antibody or deletion of the Areg gene in LepR-Cre;Brca2fl/fl mice rescued HSC defects caused by AREG. Mechanistically, AREG activated the phosphoinositide 3-kinases (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, promoted HSC cycling, and compromised HSC quiescence. Finally, we demonstrated that BM LepR+ niche cells from other DNA repair-deficient and aged mice also showed persistent DNA damage-associated overexpression of AREG, which exerts similar negative effects on HSC maintenance. Therefore, we identified an important factor that regulates HSCs function under conditions of DNA repair deficiency and aging.

An Aptamer-Functionalized DNA Circuit to Establish an Artificial Interaction between T Cells and Cancer Cells.

Nongenetic strategies that enable control over the cell-cell interaction network would be highly desired, particularly in T cell-based cancer immunotherapy. In this work, we developed an aptamer-functionalized DNA circuit to modulate the interaction between T cells and cancer cells. This DNA circuit was composed of recognition-then-triggering and aggregation-then-activation modules. Upon recognizing target cancer cells, the triggering strand was released to induce aggregation of immune receptors on the T cell surface, leading to an enhancement of T cell activity for effective cancer eradication. Our results demonstrated the feasibility of this DNA circuit for promoting target cancer cell-directed stimulation of T cells, which, consequently, enhanced their killing effect on cancer cells. This DNA circuit, as a modular strategy to modulate intercellular interactions, could lead to a new paradigm for the development of nongenetic T cell-based immunotherapy.

Wrist-ankle acupuncture combined with pain nursing for the treatment of urinary calculi with acute pain.

BACKGROUND: Urological calculi often cause renal colic, which is characterized by paroxysmal or persistent severe pain in the upper abdomen or lumbar region. Development of methods to quickly relieve these pain symptoms has garnered clinical attention. Wrist-ankle acupuncture is a type of floating acupuncture therapy administered at selected points in the carpal and ankle areas, and it has good pain-relieving effects. We used wrist-ankle acupuncture combined with pain nursing for pain intervention in patients with renal calculi to confirm its application and safety. AIM: To study the effect of wrist-ankle acupuncture combined with pain nursing in the treatment of urinary calculi with acute pain. METHODS: Eighty-two patients with urinary calculi with acute pain as the first symptom followed at our hospital from November 2019 to June 2021 were enrolled in the study and classified into two groups according to the odd and even numbers of the visit sequences, each with 41 cases. The control group received a routine nursing intervention and intramuscular injection of nonsteroidal anti-inflammatory drugs, whereas the observation group received pain management nursing and wrist-ankle acupuncture. Subsequently, the pain-relieving effect was compared between the two groups. RESULTS: The score on the visual analog scale (VAS) at 24, 48, and 72 h postintervention was decreased in both groups compared with the baseline data; moreover, the observation group scored significantly lower than the control group on the VAS at each time point after the intervention (P < 0.05). The clinical efficacy at 24 h postintervention was not significantly different between the two groups (P > 0.05). In turn, the pain recurrence rate at 72 h postintervention was lower in the observation group compared with the control group (P < 0.05). Finally, the nursing satisfaction rate in the observation group was significantly higher than that observed in the control group (P < 0.05). No serious adverse reactions occurred during the treatment and the safety of treatment was high in both groups. CONCLUSION: Wrist-ankle acupuncture combined with pain nursing for treating urolithiasis with acute pain effectively alleviated the degree of pain and reduced the recurrence rate, which was worthy of clinical application.

Spatiotemporal Epidemiology of the Gonorrhea Epidemic in Relation to Neighborhood-level Structural Factors in an Eastern Province of China, 2016-2020.

Context: Gonorrhea, a highly communicable, sexually transmitted infection, remains a major public-health concern globally. In recent years, Zhejiang province, an eastern province, has had the highest incidence of gonorrhea in China. Objective: The study intended to identify the geographic distribution patterns and spaciotemporal clustering characteristics of the disease's incidence in Zhejiang between 2016 and 2020, to understand the spatial epidemiology of gonorrhea and to pinpoint the locations with relatively high risks of gonorrhea, the hotspots, which could be the key areas for disease prevention and control. Design: The research team performed a retrospective, spaciotemporal-clustering analysis of data about newly reported gonorrhea cases from January 2016 to December 2020 in Zhejiang province, using the China Information System for Disease Control and Prevention. Setting: The study took place at the Zhejiang Provincial Institute of Dermatology in Huzhou, China. Outcome Measures: The research team: (1) used the Geographic Information System software-ArcGIS 10.8 software to draw statistical maps; (2) conducted a spatial-pattern clustering analysis at the district or county level; (3) performed an autocorrelation analysis using Getis-Ord (Gi*) statistics to detect spatial patterns and the hotspots of gonorrhea incidence; and (4) used SaTScan9.7 to analyze the space-time clusters. Results: Zhejiang province reported 85 904 gonorrhea cases from 2016 to 2020, with a male to female ratio of 3.81:1. The average annual incidence rate of gonorrhea was 30.50 per 100 000 individuals in the population, ranging from 22.73 cases to 39.65 cases, and the annual incidence showed a significant downward trend over the five years (χ2 = 16.142, P < .001). The northern and central areas had a higher incidence than the southern area did. Autocorrelation analysis showed that the gonorrhea incidence had a significantly clustered distribution (Moran's I from 0.197 to 0.295, Z score from 4.749 to 6.909, P < .001). The high-high cluster areas were mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing. The Gi* statistics further indicated that the hotspots of gonorrhea were mainly in Hangzhou, Jiaxing, and Huzhou. The Kuldorff's scan identified two clusters, mainly composed of 36 counties or districts in northern Zhejiang, such as Hangzhou and Jiaxing, and central Zhejiang, such as Jinhua and Shaoxing. Conclusions: The gonorrhea incidence rates in northern and central Zhejiang from 2016 to 2020 were higher than those in southern Zhejiang. An area of relatively higher risk for gonorrhea existed mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing, Jinhua, and Shaoxing. In the future, the research team plans to focus on strengthening the prevention and control measures against gonorrhea in those areas.

Radar Human Activity Recognition with an Attention-Based Deep Learning Network.

Radar-based human activity recognition (HAR) provides a non-contact method for many scenarios, such as human-computer interaction, smart security, and advanced surveillance with privacy protection. Feeding radar-preprocessed micro-Doppler signals into a deep learning (DL) network is a promising approach for HAR. Conventional DL algorithms can achieve high performance in terms of accuracy, but the complex network structure causes difficulty for their real-time embedded application. In this study, an efficient network with an attention mechanism is proposed. This network decouples the Doppler and temporal features of radar preprocessed signals according to the feature representation of human activity in the time-frequency domain. The Doppler feature representation is obtained in sequence using the one-dimensional convolutional neural network (1D CNN) following the sliding window. Then, HAR is realized by inputting the Doppler features into the attention-mechanism-based long short-term memory (LSTM) as a time sequence. Moreover, the activity features are effectively enhanced using the averaged cancellation method, which improves the clutter suppression effect under the micro-motion conditions. Compared with the traditional moving target indicator (MTI), the recognition accuracy is improved by about 3.7%. Experiments based on two human activity datasets confirm the superiority of our method compared to traditional methods in terms of expressiveness and computational efficiency. Specifically, our method achieves an accuracy close to 96.9% on both datasets and has a more lightweight network structure compared to algorithms with similar recognition accuracy. The method proposed in this article has great potential for real-time embedded applications of HAR.

Oral contraceptives (OCs) in combination with metformin versus OCs alone on metabolism in nonobese polycystic ovary syndrome: A meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: To compare OCs(oral contraceptives) + metformin and OCs alone for metabolic effects in nonobese polycystic ovary syndrome (PCOS) patients. METHODS: The search was performed in PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for all published studies up to 30 April 2022 and was limited to English-language articles. All randomized controlled trials (RCTs) comparing OCs + metformin and OCs alone for reproductive-age women with PCOS were included. Data were processed using Revman 5.3 software. RESULTS: Of 396 studies identified, 14 RCTs were included for analysis comprising 707 women. OCs+metformin significantly modified fasting glucose (MD = -0.21 [95% confidence interval (CI) = -0.31, -0.12], p < .00001) and fasting insulin (MD = -2.54 [95%CI = -4.04, -1.04], p = .0009) at study completion compared with OCs alone in nonobese PCOS subjects. There was no statistic difference in the homoeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol or triglycerides at study end between the two groups. CONCLUSIONS: Metformin, via its positive effects on insulin clearance, in combination with OCs, improved glucose metabolism and offered a good treatment alternative in nonobese women with PCOS.

LncRNA NIPA1-SO confers atherosclerotic protection by suppressing the transmembrane protein NIPA1.

Long non-coding RNAs (lncRNAs) are emerging as important players in gene regulation and cardiovascular diseases. However, the roles of lncRNAs in atherosclerosis are poorly understood. In the present study, we found that the levels of NIPA1-SO were decreased while those of NIPA1 were increased in human atherosclerotic plaques. Furthermore, NIPA1-SO negatively regulated NIPA1 expression in human umbilical vein endothelial cells (HUVECs). Mechanistically, NIPA1-SO interacted with the transcription factor FUBP1 and the NIPA1 gene. The effect of NIPA1-SO on NIPA1 protein levels was reversed by the knockdown of FUBP1. NIPA1-SO overexpression increased, whilst NIPA1-SO knockdown decreased BMPR2 levels; these effects were enhanced by the knockdown of NIPA1. The overexpression of NIPA1-SO reduced while NIPA1-SO knockdown increased monocyte adhesion to HUVECs; these effects were diminished by the knockdown of BMPR2. The lentivirus-mediated-overexpression of NIPA1-SO or gene-targeted knockout of NIPA1 in low-density lipoprotein receptor-deficient mice reduced monocyte-endothelium adhesion and atherosclerotic lesion formation. Collectively, these findings revealed a novel anti-atherosclerotic role for the lncRNA NIPA1-SO and highlighted its inhibitory effects on vascular inflammation and intracellular cholesterol accumulation by binding to FUBP1 and consequently repressing NIPA1 expression.

EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression.

Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.

Status of maternal serum B vitamins and pregnancy outcomes: New insights from in vitro fertilization and embryo transfer (IVF-ET) treatment.

The influence of B vitamins on human fertility and infertility treatments remains elusive. Therefore, this study investigated the association of most B vitamins with IVF-ET outcomes. A total of 216 subjects aged <35 year in their first oocyte retrieval cycle were recruited. Blood samples from the participants were collected before the oocyte pick-up procedure, and serum levels of riboflavin, niacin, pantothenic acid, vitamin B6 (including PA and PLP), folate, and methylmalonic acid (MMA) were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Endpoints were classified into three groups according to tertiles (lower, middle, and upper) of each vitamin index, and the association of the serum vitamin status with intermediate and clinical outcomes was analyzed using a generalized estimating equation model. Higher riboflavin levels were associated with elevated probabilities of high-quality embryos, as well as clinical pregnancy after embryo transfer. A greater likelihood of transferable embryos was found in the middle tertile of serum folate. Similarly, a negative correlation of serum MMA, a marker of vitamin B12 deficiency, with high-quality embryos was identified. No significance was observed for other vitamins in terms of all endpoints. Therefore, sufficient levels of pre-conception riboflavin, folate, and vitamin B12 are recommended for successful infertility treatment and pregnancy planning; further evidence is needed to confirm our conclusion.

Aptamer-Based Cancer Cell Analysis and Treatment.

Aptamers are a class of single-stranded DNA or RNA oligonucleotides that can exclusively bind to various targets with high affinity and selectivity. Regarded as "chemical antibodies", aptamers possess several intrinsic advantages, including easy synthesis, convenient modification, high programmability, and good biocompatibility. In recent decades, many studies have demonstrated the superiority of aptamers as molecular tools for various biological applications, particularly in the area of cancer theranostics. In this review, we focus on recent progress in developing aptamer-based strategies for the precise analysis and treatment of cancer cells.

Aptamer-Functionalized Nanodevices for Dynamic Manipulation of Membrane Receptor Signaling in Living Cells.

The capacity to regulate the signaling amplitude of membrane receptors in a user-defined manner would open various opportunities for precise biological study and therapy. While partial agonists enabled downtuning of cellular responses, they required esoteric optimization of the ligand-receptor interface, limiting their practical applications. Herein, we developed an aptamer-functionalized, tweezer-like nanodevice to dynamically modulate the cellular behavior through control over the distance between receptors in the dimer with no need to involve complicated structural analysis. By combining a reversible conformation switch with aptamer-based molecular recognition, this nanodevice showed excellent performance on dynamic regulation of CD28 receptor-mediated T cell immunity. With the modular design, this nanodevice could be extended to dynamically modulate the activity of other membrane receptors (e.g., c-Met), expecting to offer a new paradigm for precise study and manipulation of specific molecular events in complex biological systems.

Molecular Surveillance of Antimicrobial Resistance of Mycobacterium leprae from Leprosy Patients in Zhejiang Province, China.

Purpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province. Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy. Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases. Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.