Size control of ropivacaine nano/micro-particles by soft-coating with peptide nanosheets for long-acting analgesia.

Rationale: To meet the need of long-acting analgesia in postoperative pain management, slow-releasing formulations of local anesthetics (LAs) have been extensively investigated. However, challenges still remain in obtaining such formulations in a facile and cost-effective way, and a mechanism for controlling the release rate to achieve an optimal duration is still missing. Methods: In this study, nanosheets formed by a self-assembling peptide were used to encapsulate ropivacaine in a soft-coating manner. By adjusting the ratio between the peptide and ropivacaine, ropivacaine particles with different size were prepared. Releasing profile of particles with different size were studied in vitro and in vivo. The influence of particle size and ropivacaine concentration on effective duration and toxicity were evaluated in rat models. Results: Our results showed that drug release rate became slower as the particle size increased, with particles of medium size (2.96 ± 0.04 µm) exhibiting a moderate release rate and generating an optimal anesthetic duration. Based on this size, formulations at different ropivacaine concentrations generated anesthetic effect with different durations in rat sciatic nerve block model, with the 6% formulation generated anesthetic duration of over 35 h. Long-acting analgesia up to 48 h of this formulation was also confirmed in a rat total knee arthroplasty model. Conclusion: This study provided a facile strategy to prepare LA particles of different size and revealed the relationship between particle size, release rate and anesthetic duration, which provided both technical and theoretical supports for developing long-acting LA formulations with promising clinical application.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.

Letermovir prophylaxis reduced cytomegalovirus reactivation and resistance post umbilical cord blood transplantation.

To explore the impact of letermovir (LET) prophylaxis on cytomegalovirus (CMV) reactivation and resistance in both adult and paediatric umbilical cord blood transplantation (UCBT) patients, we retrospectively compared 43 UCBT patients who received LET as CMV prophylaxis with a historical cohort of 207 UCBT patients without LET usage. LET was administered from Day +1 to Day +100. The 180-day cumulative incidence of CMV reactivation (47.3% vs. 74.4%, p < 0.001) and the proportion of refractory CMV reactivation (15.0% vs. 42.9%, p = 0.016) were significantly lower than those in the control group. However, more frequent late CMV infection (31.0% vs. 4.3%, p = 0.002) and the 180-day cumulative incidence of Epstein-Barr virus (EBV) reactivation (9.3% vs. 3.4%, p = 0.087) were observed in UCBT patients with LET prophylaxis. Meanwhile, older age (>15 years old) and the occurrence of pre-engraftment syndrome were identified as the significant risk factors for CMV reactivation, and in patients at high risk, the incidence of CMV reactivation in the LET group was lower than that in the control group (46.7% vs. 86.5%, p < 0.001), while this decline was less pronounced among patients at low risk (47.8% vs. 62.1%, p = 0.120).

Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.

Photodynamic therapy combined with antifungal drugs against kerion: A report of six cases and literature review.

Kerion, a severe manifestation of tinea capitis caused by dermatophytes, is a fungal skin disease primarily affecting children. This report discusses six cases of pediatric kerion that were successfully treated with a combination of photodynamic therapy (PDT) and antifungal agents. Additionally, we conducted a literature review, identifying and analyzing six published reports on kerion and tinea capitis. The characteristics and efficacies of these cases are summarized. In summary, early combination therapy and proactive pre-treatment interventions proved effective in maximizing therapeutic outcomes, reducing disease duration and minimizing adverse reactions such as cicatricial alopecia. This approach has emerged as a favorable choice for the treatment of kerion.

Efficacy and safety of venlafaxine hydrochloride combined with tandospirone citrate for patients with vascular depression accompanied by somatic symptoms: An open-labeled randomized control trial.

AIMS: To explore the pharmacological treatment of vascular depression (VaDep) and whether the blood levels of neurotransmitters can reflect the VaDep severity. METHODS: VaDep patients with somatic symptoms were enrolled and randomly received venlafaxine + tandospirone (Combined Group) or venlafaxine (Monotherapy Group). The treatment efficacy was assessed by Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Patient Health Questionnaire-15 (PHQ-15). The levels of blood monoamine neurotransmitters were measured by enzyme-linked immunosorbent assay. RESULTS: Both groups reported a progressive decrease in HAMD, HAMA, and PHQ-15 scores to below the baseline after the respective treatment. Compared with the Monotherapy Group, the Combined Group reported a significant decrease in HAMD score at week 2 and markedly lower HAMA and PHQ-15 scores at weeks 1, 2, 4, and 8. Both groups showed a decrease in the levels of blood monoamine neurotransmitters at weeks 4 and 8 when compared with the baseline. A strong positive association was evident between the plasma 5-HT levels and the HAMD score. CONCLUSION: The combined therapy rapidly acts on VaDep comorbid with anxiety and somatic symptoms and significantly alleviates the anxiety and somatic symptoms. The plasma levels of 5-HT may serve as potential objective candidates in evaluating VaDep severity and the efficacy of the undertaken treatment regimen.

Photodynamic therapy successfully treats refractory onychomycosis caused by Trichosporon asahii: a case report.

Onychomycosis, a fungal infection affecting the nail, is characterized by discoloration and thickening of the nail plate and is the most prevalent nail infection globally. We present a case of onychomycosis caused by Trichosporon asahii, a less common etiology. Notably, the patient was successfully treated with a non-traditional antibacterial approach, photodynamic therapy, which has been infrequently documented in the literature for such infections.

Auditory training remodels hippocampus-related memory in adult rats.

Consequences of perceptual training, such as improvements in discriminative ability, are highly stimulus and task specific. Therefore, most studies on auditory training-induced plasticity in adult brain have focused on the sensory aspects, particularly on functional and structural effects in the auditory cortex. Auditory training often involves, other than auditory demands, significant cognitive components. Yet, how auditory training affects cognition-related brain regions, such as the hippocampus, remains unclear. Here, we found in female rats that auditory cue-based go/no-go training significantly improved the memory-guided behaviors associated with hippocampus. The long-term potentiations of the trained rats recorded in vivo in the hippocampus were also enhanced compared with the naïve rats. In parallel, the phosphorylation level of calcium/calmodulin-dependent protein kinase II and the expression of parvalbumin-positive interneurons in the hippocampus were both upregulated. These findings demonstrate that auditory training substantially remodels the processing and function of brain regions beyond the auditory system, which are associated with task demands.

Combination of concept maps and case-based learning in a flipped classroom: A mixed-methods study.

AIM: This study aimed to evaluate the impact of a hybrid learning method on the academic achievements, learning skills and experiences of undergraduate nursing students. BACKGROUND: Case-based learning is a student-centered approach that is commonly integrated into the flipped classroom model in nursing education. However, effectively combining the flipped classroom model and case-based learning into a hybrid learning format is challenging. To address this gap, this study integrated concept maps with case-based learning and the flipped classroom and evaluated the impact of this hybrid learning method on the academic achievements, learning skills and experiences of undergraduate nursing students. DESIGN: A mixed-methods approach, including a quasi-experimental study and semi-structured interviews, was employed. METHODS: A total of 277 undergraduate nursing students participated, with 136 students in the control group undergoing case-based learning and 141 students in the experimental group taught using the hybrid learning approach, which combined concept maps, case-based learning and a flipped classroom. The study assessed self-directed learning, critical thinking, learning strategy and curriculum grades in both groups before and after the intervention. Additionally, students in the experimental group participated in semi-structured interviews. RESULTS: The quantitative findings indicated that both case-based learning and the hybrid learning method (combined concept maps, case-based learning and a flipped classroom) had similar impacts on the curriculum grades, self-directed learning, cognitive maturity and learning strategy of nursing students. The qualitative results further demonstrated how the hybrid approach facilitated integrated learning, promoted self-evaluation, aided adaptation to the flipped classroom and enhanced teacher-student interaction. CONCLUSIONS: Combining case-based learning, a flipped classroom and concept maps is an effective learning approach for undergraduate nursing students. It may improve students' self-directed learning, cognitive maturity and learning strategy. Additionally, concept maps are a beneficial supplement to case-based learning and a flipped classroom in terms of guiding integrated learning, promoting self-evaluation, enhancing adaptation to a flipped classroom and increasing interaction between teachers and students and between classmates.

Utilizing metagenomic next-generation sequencing for pathogen detection and diagnosis in lower respiratory tract infections in real-world clinical practice.

BACKGROUND: Infectious etiologies of lower respiratory tract infections (LRTIs) by the conventional microbiology tests (CMTs) can be challenging. Metagenomic next-generation sequencing (mNGS) has great potential in clinical use for its comprehensiveness in identifying pathogens, particularly those difficult-to-culture organisms. METHODS: We analyzed a total of 205 clinical samples from 201 patients with suspected LRTIs using mNGS in parallel with CMTs. mNGS results were used to guide treatment adjustments for patients who had negative CMT results. The efficacy of treatment was subsequently evaluated in these patients. RESULTS: mNGS-detected microorganisms in 91.7% (188/205) of the clinical samples, whereas CMTs demonstrated a lower detection rate, identifying microorganisms in only 37.6% (77/205) of samples. Compared to CMT results, mNGS exhibited a detection sensitivity of 93.5% and 95.4% in all 205 clinical samples and 180 bronchoalveolar lavage fluid (BALF) samples, respectively. A total of 114 patients (114/201; 56.7%) showed negative CMT results, among which 92 received treatment adjustments guided by their positive mNGS results. Notably, 67.4% (62/92) of patients demonstrated effective treatment, while 25% (23/92) experienced a stabilized condition. Subgroup analysis of cancer patients revealed that 41.9% (13/31) exhibited an effective response to treatment, and 35.5% (11/31) maintained a stable condition following medication adjustments guided by mNGS. CONCLUSION: mNGS demonstrated great potential in identifying microorganisms of clinical significance in LRTIs. The rapid turnaround time and reduced susceptibility to the impact of antimicrobial administration make mNGS a valuable supplementary tool for diagnosis and treatment decision-making for suspected LRTIs in clinical practice.

Ultrasound k-nearest neighbor entropy imaging: Theory, algorithm, and applications.

Ultrasound information entropy is a flexible approach for analyzing ultrasound backscattering. Shannon entropy imaging based on probability distribution histograms (PDHs) has been implemented as a promising method for tissue characterization and diagnosis. However, the bin number affects the stability of entropy estimation. In this study, we introduced the k-nearest neighbor (KNN) algorithm to estimate entropy values and proposed ultrasound KNN entropy imaging. The proposed KNN estimator leveraged the Euclidean distance between data samples, rather than the histogram bins by conventional PDH estimators. We also proposed cumulative relative entropy (CRE) imaging to analyze time-series radiofrequency signals and applied it to monitor thermal lesions induced by microwave ablation (MWA). Computer simulation phantom experiments were conducted to validate and compare the performance of the proposed KNN entropy imaging, the conventional PDH entropy imaging, and Nakagami-m parametric imaging in detecting the variations of scatterer densities and visualizing inclusions. Clinical data of breast lesions were analyzed, and porcine liver MWA experiments ex vivo were conducted to validate the performance of KNN entropy imaging in classifying benign and malignant breast tumors and monitoring thermal lesions, respectively. Compared with PDH, the entropy estimation based on KNN was less affected by the tuning parameters. KNN entropy imaging was more sensitive to changes in scatterer densities and performed better visualizable capability than typical Shannon entropy (TSE) and Nakagami-m parametric imaging. Among different imaging methods, KNN-based Shannon entropy (KSE) imaging achieved the higher accuracy in classification of benign and malignant breast tumors and KNN-based CRE imaging had larger lesion-to-normal contrast when monitoring the ablated areas during MWA at different powers and treatment durations. Ultrasound KNN entropy imaging is a potential quantitative ultrasound approach for tissue characterization.

Rowell's syndrome with Condyloma acuminatum: A case report.

Rowell's syndrome is an autoimmune disease characterized by lupus erythematosus, erythema multiforme skin lesions, and speckled antinuclear antibody. We report the case of a woman who presented with erythema multiforme with target-type skin lesions and vulvar vegetation who fulfilled the criteria for Rowell's syndrome and condyloma acuminatum. The simultaneous occurrence of both conditions has rarely been reported in the literature.

Internal and external morphological analysis of fused-rooted mandibular second molars in the Chinese population: A micro-computed tomographic study.

This study investigated the root canal morphology of fused-rooted mandibular second molars based on the pulp chamber floor (PCF) and analysed the correlation between the external morphology of the radicular groove, and the internal morphology of the PCF and root canal configuration. A total of 291 fused-rooted teeth collected from the Chinese population were scanned using micro-computed tomography and a dental operating microscope was used for observing the PCFs. The classification of the PCF and root canal configuration were identified according to modified Min et al.'s and Gao et al.'s classifications, respectively. Additionally, a new radicular groove classification was proposed. The correlation among these morphological characteristics was investigated using the chi-square test and Fisher's exact test (p < 0.05). The results showed that 74.2% of teeth had C-shaped PCFs, while 21.0% had non-C-shaped PCFs. As for the root canal configurations, 37.5% of teeth were merging type, 40.9% were symmetrical type, and 14.8% were asymmetrical type. Statistical analysis revealed a significant correlation between the PCF types and the root canal configurations (p < 0.001). The dominant root canal types for teeth with C-shaped PCFs were merging and symmetrical types, while the asymmetrical type was not identified in non-C-shaped PCFs. In addition, significant morphological association between the root canals and radicular grooves was also revealed (p < 0.001). Teeth with different PCF morphologies exhibit specific patterns of root canal category distribution. Understanding the morphological nuances of the root canal based on the PCF can assist clinicians in predicting and identifying the canal configuration beneath the visible orifice.

Pasteurella multocida strains of a novel capsular serotype and lethal to Marmota himalayana on Qinghai-Tibet plateau in China.

Pasteurella multocida is a zoonotic pathogen causing serious diseases in humans and animals. Here, we report P. multocida from wildlife on China's Qinghai-Tibet plateau with a novel capsular serotype, forming a single branch on the core-genome phylogenetic tree: four strains isolated from dead Himalayan marmot (Marmota himalayana) and one genome assembled from metagenomic sequencing of a dead Woolly hare (Lepus oiostolus). Four of the strains were identified as subspecies multocida and one was septica. The mouse model showed that the challenge strain killed mice within 24 h at an infectious dose of less than 300 bacteria. The short disease course is comparable to septicemic plague: the host has died before more severe pathological changes could take place. Though pathological changes were relatively mild, cytokine storm was obvious with a significant rise of IL-12p70, IL-6, TNF-αand IL-10 (P < 0.05). Our findings suggested P. multocida is a lethal pathogen for wildlife on Qinghai-Tibet plateau, in addition to Yersinia pestis. Individuals residing within the M. himalayana plague focus are at risk for P. multocida infection, and public health warnings are necessitated.

A Case of Eosinophilic Pustular Folliculitis Misdiagnosed as Eczema.

Eosinophilic pustular folliculitis (EPF) is a rare skin disease. The typical skin lesions of classic EPF are localized on the upper limbs' face, trunk, and extensor surfaces. However, when the skin lesions initially appear on the palms and soles, it is not easy to diagnose as EPF. Here, we report a case of a male patient who presented with erythematous plaques, pustules, and crusted erosions on the hands and feet, which were misdiagnosed as eczema ten years ago. Over ten years, the patient experienced recurrent erythematous patches with bumps and itching on the face, trunk, and extremities after improving the hand and foot lesions. A histopathological biopsy was performed to establish a definitive diagnosis, revealing pustules formed by eosinophilic infiltrates within the hair follicles. The diagnosis was confirmed as eosinophilic pustular folliculitis. The patient was treated with oral indomethacin at a dosage of 75mg/day, resulting in the disappearance of the skin lesions. After a 3-month follow-up, no recurrence was observed.

Adjuvanted SARS-CoV-2 spike protein vaccination elicits long-lived plasma cells in nonhuman primates.

Durable humoral immunity is mediated by long-lived plasma cells (LLPCs) that reside in the bone marrow. It remains unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein vaccination is able to elicit and maintain LLPCs. Here, we describe a sensitive method to identify and isolate antigen-specific LLPCs by tethering antibodies secreted by these cells onto the cell surface. Using this method, we found that two doses of adjuvanted SARS-CoV-2 spike protein vaccination are able to induce spike protein-specific LLPC reservoirs enriched for receptor binding domain specificities in the bone marrow of nonhuman primates that are detectable for several months after vaccination. Immunoglobulin gene sequencing confirmed that several of these LLPCs were clones of memory B cells elicited 2 weeks after boost that had undergone further somatic hypermutation. Many of the antibodies secreted by these LLPCs also exhibited improved neutralization and cross-reactivity compared with earlier time points. These findings establish our method as a means to sensitively and reliably detect rare antigen-specific LLPCs and demonstrate that adjuvanted SARS-CoV-2 spike protein vaccination establishes spike protein-specific LLPC reservoirs.

An Automatic Needle Puncture Path-Planning Method for Thermal Ablation of Lung Tumors.

Computed tomography (CT)-guided thermal ablation is an emerging treatment method for lung tumors. Ablation needle path planning in preoperative diagnosis is of critical importance. In this work, we proposed an automatic needle path-planning method for thermal lung tumor ablation. First, based on the improved cube mapping algorithm, binary classification was performed on the surface of the bounding box of the patient's CT image to obtain a feasible puncture area that satisfied all hard constraints. Then, for different clinical soft constraint conditions, corresponding grayscale constraint maps were generated, respectively, and the multi-objective optimization problem was solved by combining Pareto optimization and weighted product algorithms. Finally, several optimal puncture paths were planned within the feasible puncture area obtained for the clinicians to choose. The proposed method was evaluated with 18 tumors of varying sizes (482.79 mm3 to 9313.81 mm3) and the automatically planned paths were compared and evaluated with manually planned puncture paths by two clinicians. The results showed that over 82% of the paths (74 of 90) were considered reasonable, with clinician A finding the automated planning path superior in 7 of 18 cases, and clinician B in 9 cases. Additionally, the time efficiency of the algorithm (35 s) was much higher than that of manual planning. The proposed method is expected to aid clinicians in preoperative path planning for thermal ablation of lung tumors. By providing a valuable reference for the puncture path during preoperative diagnosis, it may reduce the clinicians' workload and enhance the objectivity and rationality of the planning process, which in turn improves the effectiveness of treatment.