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Neutrinoless double beta decay (0νββ) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νββ) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νββ decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.07±0.02(stat)±0.11(syst)]×10^{18}  yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νββ decay rate in ^{100}Mo. In addition, we constrain higher-order corrections to the spectral shape, which provides complementary nuclear structure information. We report a novel measurement of the shape factor ξ_{3,1}=0.45±0.03(stat)±0.05(syst) based on a constraint on the ratio of higher-order terms from theory, which can be reliably calculated. This is compared to theoretical predictions for different nuclear models. We also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νββ decay.

Liyan Sun,1 Jinshuai Lan,1,2 Zhe Li,1,2 Ruifeng Zeng,1,2 Yi Shen,1 Tong Zhang,1,2 Yue Ding1– 3 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3National Innovation Platform for Medical Industry-Education Integration, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Yue Ding; Tong Zhang, Email dingyue-2001@hotmail.com; zhangtongshutcm@hotmail.comAbstract: Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery. Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. Nano-delivery systems increase drug concentration at the tumor site by improving pharmacological activity and tissue distribution, enhancing drug bioavailability. Organic nanocarriers have advantages for berberine delivery including biocompatibility, encapsulation, and controlled release of the drug. While the advantages of inorganic nanocarriers for berberine delivery mainly lie in their efficient loading ability of the drug and their slow release ability of the drug. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery.Keywords: berberine, anti-cancer, nano drug delivery system, combination therapy

Xiawan Yang,1– 3,* Yingying Shen,1– 3,* Tonglin Hu,1– 3 Hangchao Li,1– 3 Yun Zhang,1– 3 Yiping Shen,1– 3 Dijiong Wu1– 4 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dijiong Wu; Yiping Shen, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Youdian Road No. 54, Hangzhou, 310006, Zhejiang, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn; shenyp_@126.comBackground: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens.Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission.Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation.Keywords: carrimycin, perianal infection, acute myeloid leukemia, immunomodulatory

Lianjie Miao, Songwei Feng, Bo Ding, Ke Zhang, Yue Ding, Yang Shen Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Yang Shen, Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210096, People’s Republic of China, Email shenyang@seu.edu.cnPurpose: The aim of this study was to analyze the survival of patients with endometrial cancer diagnosed after a prior cancer and identify risk factors of endometrial cancer death in this population.Methods: Totally 1371 women diagnosed with second primary endometrial cancer (SPEC) between 2004 and 2015 were identified using the SEER database. Clinicopathological characteristics were collected, and Fine and Gray regression model was employed to assess the impact of treatment for the first primary cancer (FPC) and SPEC on the mortality of endometrial cancer patients. After propensity score matching (PSM), patients diagnosed with single primary endometrial cancer and SPEC between 2004 and 2015 were included as the second cohort. Kaplan-Meier and Cox survival risk models were used to assess the influence of previous cancer history on survival.Results: Patients previously diagnosed as lung cancer exhibited the lowest overall survival (OS). A diagnostic interval of ≥ 3 years was significantly associated with higher mortality from SPEC compared with that < 3 years. Surgical treatment for SPEC was linked to a reduced risk of endometrial cancer-specific mortality (ECSM) and non-ECSM. Conversely, radiotherapy and chemotherapy were associated with an increased risk of ECSM. The 1-, 3-, and 5-year OS rates of patients with SPEC were significantly lower than those with single primary endometrial cancer whether before or after PSM. Univariate and multivariate analyses further demonstrated that endometrial cancer, either as FPC or SPEC, was independently associated with an increased risk for endometrial cancer-specific survival (ECSS) and OS.Conclusion: Chemotherapy and radiotherapy for SPEC can elevate the risk of ECSM. Whether as FPC or SPEC, endometrial cancer is demonstrated to be a significant independent risk factor for ECSS and OS.Keywords: second primary cancer, endometrial cancer, risk factor, overall survival, SEER database

Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Ya Shen,1,2,&ast; Shun-Shun Cui,3,&ast; Xiao-Bao Teng,2,&ast; Ming-Feng Han,2 Yan-Bei Zhang1 1Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, 236000, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Fuyang People’s Hospital, Fuyang, 236000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Bei Zhang, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, No. 218 of Jixi Road, Shushan District, Hefei, 230000, People’s Republic of China, Tel +86-13093340370, Email zhangyanbeizyb@126.com Ming-Feng Han, Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, No.1088 of Yinghexi Road, Yingzhou District, Fuyang, 236000, People’s Republic of China, Tel +86-16655800262, Email mingfeng_han@126.comObjective: The aim of this study was to assess the prevalence of Tropheryma whipplei (TW) infection in the population and to investigate the clinical symptoms, as well as the laboratory and imaging characteristics of patients testing positive for TW using next-generation sequencing (NGS).Methods: A retrospective review was conducted on 1346 bronchoalveolar lavage fluid (BALF) samples collected between January 2021 and September 2023. The case group comprised patients with TW detected using NGS while the control group included 65 randomly chosen Gram-positive bacterial infection patients without TW. Comparative analyses were carried out on the basic demographics, laboratory parameters, and imaging findings between the two groups. Additionally, the case group underwent an in-depth examination of underlying diseases, pathogens, final diagnoses, treatment strategies.Results: The case group comprised of 51 patients with TW, constituting 3.8% of the total. There was no significant difference in gender and age between the case and control groups (P = 0.84, P = 0.07). Symptoms such as coughing, expectoration, wheezing, fever, and hemoptysis are less commonly detected in the case group with a higher incidence of chest pain when compared to the control group (P > 0.05). The case group exhibited decreased albumin levels and increased C-reactive protein and D-dimer levels compared to normal levels. Imaging findings in the case group commonly included nodules, patchy images, and interstitial changes, the most common underlying disease is cardiovascular disease, and the most frequently co-occurring pathogen is the human herpesvirus. Among the case group, 27 patients received a final diagnosis of pneumonia, and 3 patients clinically diagnosed with Whipple’s disease demonstrated improvement in both symptoms and imaging after treatment.Conclusion: NGS revealed a relatively low overall detection rate of TW-positive patients using BALF. TW was more prevalent in middle-aged and elderly male patients characterized by symptoms such as cough, expectoration, shortness of breath, and fever. Chest imaging in these cases typically showed nodules and interstitial changes.Keywords: bronchoalveolar lavage fluid, feature, image, NGS, Tropheryma whipplei

Dongru Du,1– 3,&ast; Bi Ran,1– 3,&ast; Dan Xu,1– 3 Lian Liu,1– 3 Xueru Hu,1– 3 Tingting Zeng,1– 3 Yongchun Shen,1– 3 Fengming Luo1– 4 1Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, 610200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongchun Shen; Fengming Luo, Tel +86 28 8542 2350, Fax +86 28 8558 2944, Email shen_yongchun@126.com; fengmingluo@outlook.comBackground: Sex steroid hormones, including testosterone and estradiol, play significant roles in various aspects of pulmonary health and diseases. However, although there were a few studies trying to link sex hormones with COPD, their effect remained limited due to small sample size and insufficient causal results. This study aims to investigate the association between sex hormones and chronic obstructive pulmonary disease (COPD) based on the National Health and Nutrition Examination Survey (NHANES) database and evaluate causality via a two-sample Mendelian randomization (MR).Methods: Data from NHANES 2013– 2016 were enrolled for the cross-sectional study. The association between sex hormones and COPD was evaluated via multivariable logistic regression. Sex-stratified analysis, subgroup analyses and interaction tests were performed to further evaluate the correlation. For MR analysis, data were collected from genome-wide association studies and FinnGen datasets. The inverse-variance-weighted (IVW) approach, along with four other approaches, was applied in the analysis. Further sensitivity analysis was conducted to assess the existence of pleiotropy and heterogeneity.Results: 7,617 eligible participants were enrolled in the cross-sectional analysis. Negative associations were observed in both testosterone-COPD (OR 0.770, 95% CI 0.626, 0.948, p = 0.018) and estradiol-COPD (OR 0.794, 95% CI 0.688, 0.915, p = 0.005) relationships after covariate adjustments. However, the results from IVW-MR analysis showed that no causal relationship was observed in either the testosterone-COPD (OR 0.83, 95% CI 0.53, 1.29, p = 0.407) or estradiol-COPD (OR 0.74, 95% CI 0.23, 2.38, p = 0.616) relationship, which was also supported by the other four approaches (all p values > 0.05).Conclusion: Although a significant negative association was observed between sex hormones and COPD, the results of MR analysis did not support the causality of this relationship. Our study suggested that sex hormones may indirectly rather than directly affect the development of COPD via potential covariates, which warranted further investigations.Keywords: sex steroid hormones, testosterone, estradiol, chronic obstructive pulmonary disease, NHANES, Mendelian randomization

Kunhui Sun,1,2,&ast; Bing Wang,2,&ast; Mengnan Li,2 Yanli Ge,1 Lijun An,2 Duanna Zeng,2 Yuhan Shen,1 Ping Wang,2 Meifang Li,2 Xuelei Hu,1 Xie-An Yu1,2 1Key Laboratory for Green Chemical Engineering Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, People’s Republic of China; 2NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanli Ge; Xie-An Yu, Email geyanli@wit.edu.cn; yuxieanalj@126.comBackground: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors.Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT).Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer.Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy. Keywords: multimodality imaging guided synergistic cancer phototherapy, FL/PA/IR multimodal imaging, PDT/PTT dual synergistic therapy pathway, Zn phthalocyanine derivant

Haotian Zhou,1,2,&ast; Yaji Yang,1,2,&ast; Yanhao Zhang,3 Feilong Li,1,2 Yidong Shen,4 Leilei Qin,1,2 Wei Huang1,2 1Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3College of Pharmacy, Army Military Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Orthopaedics, The First People’s Hospital of Yancheng, Yancheng, 224000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leilei Qin; Wei Huang, Email 253505921@qq.com; huangwei68@263.netAbstract: Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery, posing significant challenges to orthopedic surgeons. Due to the lack of a definitive diagnostic gold standard, timely treatment initiation is problematic, resulting in substantial economic burdens on patients and society. In this review, we thoroughly analyze the complexities of PJI and emphasize the importance of accurate diagnosis and effective treatment. The article specifically focuses on the advancements in diagnostic techniques, ranging from traditional pathogen culture to advanced molecular diagnostics, and discusses their role in enhancing diagnostic accuracy. Additionally, we review the latest surgical management strategies, including everything from debridement to revision surgeries. Our summary aims to provide practical information for the diagnosis and treatment of PJI and encourages further research to improve diagnostic accuracy and treatment outcomes.Keywords: arthroplasty, periprosthetic joint infection, PJI, molecular diagnosis, pathogenesis diagnosis, antibiotic application, recurrence of infection

Mengjuan Sun,1,&ast; Jun Wei,1,&ast; Yanhui Su,1,&ast; Yangjingwan He,1 Liang Ge,1 Yan Shen,1 Bohui Xu,2 Yanlong Bi,3 Chunli Zheng1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, People’s Republic of China; 3Pediatric Intensive Care Unit, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Zheng; Yanlong Bi, Email zhengchunli@cpu.edu.cn; pulong123@163.comPurpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects.Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs).Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug’s circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug’s efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions.Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM’s poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.Keywords: acute lung injury, simvastatin, respiratory distress syndrome, pH response

Yan Ji,1 Haorong Li,1 Jiguo Li,2 Guangqiang Yang,1 Wenli Zhang,1 Yan Shen,1 Bohui Xu,3 Jianping Liu,1 Jingyuan Wen,4 Wenting Song1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Nanjing Miaobang Meiye Enterprise Management Co, LTD, Nanjing, People’s Republic of China; 3School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China; 4School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New ZealandCorrespondence: Wenting Song, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China, Email songwenting908@163.com Jingyuan Wen, School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New Zealand, Email j.wen@auckland.ac.nzPurpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris.Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo.Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy.Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.Keywords: acne vulgaris, azelaic acid, hair follicle, micro/nanocrystals, targeted delivery

Sida Chen, Ling Wen, Jintao Ou, Yuting Lai, Yan Shen Department of Respiratory, Shenzhen Longgang Central Hospital, Shenzhen, Guangdong, 518000, People’s Republic of ChinaCorrespondence: Yan Shen, Shenzhen Longgang Central Hospital 6082 Longgang Boulevard (Longgang Section), Longgang District, Shenzhen, Guangdong, 518000, People’s Republic of China, Tel +86-0755-84806933-5901, Email shenyan5902@163.comBackground: Pulmonary infections are significant global health burdens, and conventional diagnostic methods (culture and polymerase chain reaction), are often limited by slow results and low sensitivity. Metagenomic next-generation sequencing (mNGS) offers a rapid, comprehensive alternative for identifying diverse pathogens, including rare and mixed infections. Thus, we assessed the diagnostic performance of mNGS in pulmonary infections, compared the findings with those of traditional pathogen detection methods, and explored its potential to enhance clinical diagnostics and patient care.Methods: We collected samples from 125 immunocompromised patients diagnosed with pulmonary infection at the Department of Respiratory Medicine of Shenzhen Longgang Central Hospital from March 2020 to July 2022. We compared the rate of pathogen positivity and pathogen distribution between conventional pathogen detection methods and mNGS using samples including sputum, blood, and bronchoalveolar lavage fluid.Results: Among the 125 cases of unexplained pulmonary infection, 82 (65.6%) and 40 (32.0%) tested positive for pathogens using mNGS and routine culture, respectively (P < 0.05). Both methods of pathogen detection were positive in 28 (22.4%) cases (complete match, 9; complete mismatch, 13; partial match, 6). However, 43.2% of cases only tested positive using mNGS, 9.4% only tested positive using routine tests, and 24.8% tested negative using both methods. A viral infection was present in 55.2% of cases. The detection rate of mycobacteria using mNGS (12.8%) was higher than that using conventional pathogen detection methods (5.6%).Conclusion: mNGS technology enhances pathogen detection in unexplained pulmonary infections, enabling targeted antimicrobial therapy and consequently helping to reduce broad-spectrum antibiotic use, aligning treatments more closely with the causative pathogens. Thus, mNGS offers significant clinical value by improving treatment efficacy and potentially reducing antibiotic resistance in pulmonary infection cases.Keywords: mNGS, Unexplained pulmonary infection, Pathogens, BALF

Shaofei Zhang,1– 3,&ast; Xu Ouyang,1– 3,&ast; Kefei Yang,2,3,&ast; Yunyun Shen,2,3 Siyuan Zheng,1– 3 Ruoqi Wang,1– 3 Xuanlian Sheng,1– 3 Menglin Ge,1– 3 Meng Yang,1– 3 Xiaoqin Zhou1,2 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei City, People’s Republic of China; 2Second Affiliated Hospital of Anhui Medical University, Hefei City, People’s Republic of China; 3Chaohu Hospital of Anhui Medical University, Hefei City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqin Zhou, Second Affiliated Hospital of Anhui Medical University, Hefei City, People’s Republic of China, Tel +8613865913378, Email zhouxqlulu@126.comPurpose: In schizophrenia, aggressive conduct is frequent. And depressed mood can also contribute to the occurrence of aggressive behaviors. The aim of this study was to investigate the risk factors for the occurrence of aggression in stable schizophrenia patients in rural China, mainly to investigate the role of depressed mood in the occurrence of aggression in schizophrenia patients.Patients and Methods: This is a cross-sectional study conducted in the townships surrounding Chaohu City, Anhui Province, China. Patients’ depressive mood was evaluated using the PHQ-9 (The 9-item Patient Health Questionnaire). Patients’ aggressiveness was evaluated using the Modified Overt Aggression Scale (MOAS). A score of ≥ 4 was used as a threshold and divided into aggressive and non-aggressive groups.Results: This study comprised a total of 821 schizophrenia patients. Among them, the prevalence of having aggressive behavior was 18.8%. After correcting for confounders, logistic regression analysis showed that low education level (OR=0.470, 95% CI 0.254– 0.870; p=0.016), living with family (OR=0.383, 95% CI 0.174– 0.845; p=0.017) depressed mood (OR=1.147, 95% CI 1.112– 1.184; p< 0.001) was significantly associated with the risk of aggressive behavior in patients with schizophrenia. Multivariate linear regression indicated that higher levels of aggression were linked with lower levels of education and higher depressive mood.Conclusion: This study suggests that aggression is more common in patients with stable schizophrenia, and lower levels of education and higher levels of depression are associated risk factors for its occurrence. Living alone may be helpful in reducing the likelihood of aggression.Keywords: schizophrenia depression aggression Chinese

Zhilin Sha,1,&ast; Qingxiang Gao,1,&ast; Lei Wang,2,&ast; Ni An,3 Yingjun Wu,1 Dong Wei,4 Tong Wang,5 Chen Liu,1 Yang Shen1 1Department I of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of General Surgery, Yancheng Hospital of Traditional Chinese Medicine, Yancheng, Jiang Su, People’s Republic of China; 3Department of Anesthesiology, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of General Surgery (Second Ward), the No.1 People’s Hospital of Pinghu, Pinghu, Zhe Jiang, People’s Republic of China; 5Department of Anesthesiology, No.32295 Troop of Chinese PLA, Liaoyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, No. 700 of North Moyu Road, Jia Ding District, Shanghai, 201823, People’s Republic of China, Email drbruceshen@163.com Chen Liu, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, No. 700 of North Moyu Road, Jia Ding District, Shanghai, 201823, People’s Republic of China, Email dinoliu@126.comBackground: Colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Liver metastasis (LM) is the main cause of death in patients with CRC. Therefore, identification of patients with the greatest risk of liver metastasis is critical for early treatment and reduces the mortality of patients with colorectal cancer liver metastases.Methods: Initially, we characterized cell composition through single-cell transcriptome analysis. Subsequently, we employed copy number variation (CNV) and pseudotime analysis to delineate the cellular origins of LM and identify LM-related epithelial cells (LMECs). The LM-index was constructed using machine learning algorithms to forecast the relative abundance of LMECs, reflecting the risk of LM. Furthermore, we analyzed drug sensitivity and drug targeted gene expression in LMECs and patients with a high risk of LM. Finally, functional experiments were conducted to determine the biological roles of metastasis-related gene in vitro.Results: Single-cell RNA sequencing analysis revealed different immune landscapes between primary CRC and LM tumor. LM originated from chromosomal variants with copy number loss of chr1 and chr6p and copy number gain of chr7 and chr20q. We identified the LMECs cluster and found LM-associated pathways such as Wnt/beta-catenin signaling and KRAS signaling. Subsequently, we identified ten metastasis-associated genes, including SOX4, and established the LM-index, which correlates with poorer prognosis, higher stage, and advanced age. Furthermore, we screened two drugs as potential candidates for treating LM, including Linsitinib_1510, Lapatinib_1558. Immunohistochemistry results demonstrated significantly elevated SOX4 expression in tumor samples compared to normal samples. Finally, in vitro experiments verified that silencing SOX4 significantly inhibited tumor cell migration and invasion.Conclusion: This study reveals the possible cellular origin and driving factors of LM in CRC at the single cell level, and provides a reference for early detection of CRC patients with a high risk of LM.Keywords: colorectal cancer, liver metastasis, single-cell sequencing, SOX4, prognostic

Yingying Shen,1,2,&ast; Junmin Cao,3,&ast; Tonglin Hu,1,2 Xiawan Yang,1,2 Yuechao Zhao,1,2 Yiping Shen,1,2 Baodong Ye,1,2 Yunsong Yu,4 Dijiong Wu1,2 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dijiong Wu, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn Yunsong Yu, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310024, People’s Republic of China, Tel +8613805790432, Email yvys119@zju.edu.cnBackground: Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam. The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment. Herein, we reported a case of perianal infection with hypervirulent ST463 Pseudomonas aeruginosa.Case Presentation: The case is a 32-year-old acute myeloid leukemia (AML) patient with fever and septic shock during hematopoietic stem cell transplantation (HSCT), and the pathogen was finally identified as a highly virulent sequence type 463 (ST463) P. aeruginosa harboring carbapenem-resistant genes blaAFM-1 and blaKPC-2, which was detected in the bloodstream and originated from a perianal infection. The strain was resistant to ceftazidime/avibactam but successfully treated with polymyxin B, surgical debridement, and granulocyte engraftment after HSCT. The AML was cured during the 19-month follow-up.Conclusion: This case emphasizes the importance of metagenomic next-generation sequencing (mNGS) and whole-genome sequencing (WGS) in identifying microbes with rare resistant genes, and managing CRPA, especially in immunocompromised patients. Polymyxin B may be the least resistant option.Keywords: carbapenem-resistant pseudomonas aeruginosa, blaAFM, blaKPC, ST463

Guanjin He,1,&ast; Qifeng Yang,2,&ast; Yuyang Shen,3 Lanzhi Zhang,2 Jingping Wu,2 Hongbin Cheng1 1Dermatology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Medical Aesthetic Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Traditional Chinese Medicine Department, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingping Wu; Hongbin Cheng, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shi-Er-Qiao Road, Jinniu District, Chengdu, People’s Republic of China, Tel +86 15928747715 ; +86 13880848134, Email jingpingwu2022@163.com; chenghongbin@cdutcm.edu.cnAbstract: Our team used a new kite flap preparation method to repair wounds after the removal of a benign facial tumor with satisfactory aesthetic results. Thus, this modified kite flap has significant value in facial trauma repair.Keywords: facial wound repair, modified kite flap, experience, case series

The CUPID-Mo experiment, located at the Laboratoire Souterrain de Modane (France), was a demonstrator experiment for CUPID. It consisted of an array of 20Li2Mo100O4 (LMO) calorimeters, each equipped with a Ge light detector for particle identification. In this work, we present the result of a search for two-neutrino and neutrinoless double-β decays of Mo100 to the first 0+ and 2+ excited states of Ru100 using the full CUPID-Mo exposure (2.71kgyr of LMO). We measure the half-life of 2νββ decay to the 01+ state as T1/22ν→01+=(7.5±0.8(stat.)-0.3+0.4(syst.))×1020yr. The bolometric technique enables measurement of the electron energies as well as the γ rays from nuclear deexcitation and this allows us to set new limits on the two-neutrino decay to the 21+ state of T1/22ν→21+>4.4×1021yr(90% c.i.) and on the neutrinoless modes of T1/20ν→21+>2.1×1023yr(90% c.i.), T1/20ν→01+>1.2×1023yr(90% c.i.). Information on the electrons' spectral shape is obtained, which allows us to make the first comparison of the single and higher state dominance 2νββ decay models for the 01+ excited state of Ru100.

CUPID-Mo, located in the Laboratoire Souterrain de Modane (France), was a demonstrator for the next generation 0 νββ decay experiment, CUPID. It consisted of an array of 20 enriched Li 2100 MoO 4 bolometers and 20 Ge light detectors and has demonstrated that the technology of scintillating bolometers with particle identification capabilities is mature. Furthermore, CUPID-Mo can inform and validate the background prediction for CUPID. In this paper, we present a detailed model of the CUPID-Mo backgrounds. This model is able to describe well the features of the experimental data and enables studies of the 2 νββ decay and other processes with high precision. We also measure the radio-purity of the Li 2100 MoO 4 crystals which are found to be sufficient for the CUPID goals. Finally, we also obtain a background index in the region of interest of 3.7 -0.8+0.9 (stat) -0.7+1.5 (syst) ×10-3 counts/ Δ EFWHM/ mol iso/ year , the lowest in a bolometric 0 νββ decay experiment.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

Ultrashort energetic terahertz (THz) pulses have created an exciting new area of research on light interactions with matter. For material studies in small laboratories, widely tunable femtosecond THz pulses with peak field strength close to MV cm-1 are desired. Currently, they can be largely acquired by optical rectification and difference frequency generation in crystals without inversion symmetry. We describe in this paper a novel scheme of THz pulse generation with no frequency tuning gap based on Raman-resonance-enhanced four-wave mixing in centrosymmetric media, particularly diamond. We show that we could generate highly stable, few-cycle pulses with near-Gaussian spatial and temporal profiles and carrier frequency tunable from 5 to >20 THz. They had a stable and controllable carrier-envelop phase and carried ~15 nJ energy per pulse at 10 THz (with a peak field strength of ~1 MV cm-1 at focus) from a 0.5-mm-thick diamond. The measured THz pulse characteristics agreed well with theoretical predictions. Other merits of the scheme are discussed, including the possibility of improving the THz output energy to a much higher level.

Guocan Yu,1 Yanqin Shen,2 Liwei Yao,2 Xudong Xu1 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Nursing, Hangzhou Red Cross Hospital, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Liwei Yao; Xudong Xu, Email ylwmed@163.com; xuxudong234@163.comPurpose: This study aimed to evaluate the efficacy of nanopore sequencing for diagnosing pulmonary tuberculosis (PTB) using smear-negative clinical specimens.Methods: We conducted a retrospective study based on a review of patient medical records to assess the accuracy of nanopore sequencing as a diagnostic tool for smear-negative PTB. Compared with clinical diagnosis, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of nanopore sequencing.Results: A total of 647 patients were evaluated. Nanopore sequencing demonstrated an overall sensitivity of 91.7%, specificity of 85.3%, PPV of 95.1%, NPV of 76.4%, and AUC of 0.88. Notably, the overall diagnostic accuracy of nanopore sequencing was significantly higher than that of Mycobacterium tuberculosis (MTB) culture technique.Conclusion: Nanopore sequencing exhibited satisfactory overall diagnostic accuracy for smear-negative PTB, regardless of MTB culture status. Therefore, if conditions permit, nanopore sequencing is recommended as a diagnostic method for smear-negative PTB.Keywords: nanopore sequencing, smear-negative specimens, pulmonary tuberculosis, diagnostic accuracy