Objective:To summarize the clinical characteristics and treatment experience of patients with botulism after cosmetic botulinum toxin injection.Methods:A retrospective study was conducted on patients admitted to the Department of Medical Aesthetic and Plastic Surgery of the Fifth Affiliated Hospital of Zhengzhou University for botulism after cosmetic botulinum toxin injection between January 1, 2023, and October 31, 2024. Clinical data and treatment regimens were collected. Patients received botulinum antitoxin injection, neurotrophic therapy, nutrition supplementation, modulation and enhancement of cellular immune function, and systemic supportive care based on their condition. Prior to antitoxin administration, a skin test was performed. Patients with a negative test received intramuscular injections of 10 000 U of antitoxin serum every 12 hours, while those with a positive result underwent a desensitization protocol. The cessation criterion was significant improvement of toxic symptoms. Data collected included age, gender, region, time of presentation, injection location, brand and type of toxin, injection time, sites and dose of injection, time to onset of initial symptoms, main symptoms, skin test result for antitoxin, dosage of antitoxin administered, length of hospital stay, adverse reactions and prognosis. Data analysis was performed using GraphPad Prism Version 10.2.0.Results:A total of 179 patients were included, with 8 cases in 2023 and 171 cases in 2024. The majority were female (97.2%, 174 cases). The age range was 18-62 years, with a median age of 35 years; the highest proportion was in the 20-40 age group (71.5%, 128 cases). Patients were from 23 different provinces, autonomous regions, and municipalities directly under the central government in China. The injected product was mostly an unspecified brand of botulinum toxin (57.5%, 103 cases). Injections were primarily administered in non-medical institutions, with beauty salons or private studios accounting for 88.8% (159 cases). Injection sites included the platysma (92 cases), masseter muscle (82 cases), orbicularis oculi muscle (82 cases), frontalis muscle (67 cases), among others, with some patients receiving injections at multiple sites. 69 cases (38.5%) of patients were unaware of the injected dose; for the remaining cases, based on information provided, the injected doses were all within the safe range. The incubation period was mostly 1-7 days. The main symptoms included fatigue (171 cases), dysphagia (137 cases), dizziness (101 cases), blurred vision (76 cases), and difficulty opening eyes (66 cases). 176 patients received botulinum antitoxin treatment; 82 cases (46.6%) had a positive skin test and received desensitization injections, while 94 cases (53.4%) had a negative test. The total dosage of antitoxin used ranged from 10 000 U to 240 000 U. Three patients received only adjuvant therapy such as neurotrophic support. Adverse reactions during treatment primarily included induration at the injection site and serum sickness, all of which resolved after symptomatic treatment with antihistamines, steroids, etc. The hospital stay ranged from 1 to 24 d, with an average of 4.6 d. Upon discharge, symptoms in all patients had alleviated or resolved. At the 6-month follow-up after discharge, 14 patients were lost to follow-up; the remaining patients recovered well with no other complications.Conclusion:Poisoning incidents due to the illegal or improper use of botulinum toxin are increasing. Administration of botulinum antitoxin is an effective means to ameliorate intoxicating symptoms. Patients should seek timely medical intervention and receive antitoxin treatment as early as possible. Desensitization administration does not affect the efficacy of the antitoxin.

Objective:To understand the molecular evolutionary characteristics of the recombinant strain GII.3[P12] of norovirus acute gastroenteritis outbreaks and aggregated outbreaks in China from 2022 to 2023.Methods:Epidemiological information, case information, clinical samples, as well as detection and genotyping information of norovirus outbreaks and aggregated outbreaks from 2022 to 2023 were collected; positive samples of the GII.3[P12] recombinant strain were subjected to nucleic acid extraction, whole-genome amplification, and sequence analysis; and homology simulation method were used to construct a three-dimensional structure and predict antigenic epitopes.Results:From January 2022 to December 2023, a total of 1 136 norovirus outbreaks and aggregated outbreaks were reported in China′s norovirus outbreak surveillance network, and genotyping result were successfully obtained for 942 outbreaks, with GII dominating, accounting for 76.0% (716/942), and the proportion of GI and mixed genotypes being 15.8% (149/942) and 8.2% (77/942). Norovirus outbreaks caused by GII were dominated by GII.3[P12] (22.5%, 161/716), while other major genotypes included GII.17[P17] (18.7%, 134/716), GII.4_Sydney 2012[P16] (11.6%, 83/716) and GII.6[P7] ( 11.3%, 81/716). 2022-2023 Outbreaks caused by GII.3[P12] were concentrated in February-March (54.0%, 87/161), with the main outbreaks occurring in nursery and primary schools (87.5%), the mode of transmission was mainly human-to-human (68.9%), and the main susceptible population was children aged 3-7 years (93.3%). In this study, the genome sequences of 25 GII.3[P12] recombinant strains were obtained, and according to the phylogenetic analysis, it was shown that the GII.3[P12] recombinant strains in China in 2022-2023 belonged to the Cluster IV cluster of sublineage b (7 strains) and sublineage c (18 strains). A total of 11 linear and 8 conformational epitopes were predicted by epitope prediction analysis, and the predicted linear and conformational epitopes had overlapping positions, and each conformational epitope was part of the predicted linear epitope with conserved potential antigen-binding and receptor-binding sites.Conclusions:The recombinant strain GII.3[P12] is one of the epidemic strains that will cause outbreaks and clusters of norovirus in China in 2022-2023, and its genome did not undergo significant mutation.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

This article reports two patients who developed abdominal wall endometriosis(AWE) after cesarean section and had the need for abdominal wall plastic surgery. The problems of AWE treatment and abdominal shape improvement were simultaneously solved through a single combined surgery (abdominal wall plastic surgery + resection of endometriotic nodules), and the follow-up at half a year after the operation presented good appearance.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

This article reports two patients who developed abdominal wall endometriosis(AWE) after cesarean section and had the need for abdominal wall plastic surgery. The problems of AWE treatment and abdominal shape improvement were simultaneously solved through a single combined surgery (abdominal wall plastic surgery + resection of endometriotic nodules), and the follow-up at half a year after the operation presented good appearance.

Objective:To summarize the clinical characteristics and treatment experience of patients with botulism after cosmetic botulinum toxin injection.Methods:A retrospective study was conducted on patients admitted to the Department of Medical Aesthetic and Plastic Surgery of the Fifth Affiliated Hospital of Zhengzhou University for botulism after cosmetic botulinum toxin injection between January 1, 2023, and October 31, 2024. Clinical data and treatment regimens were collected. Patients received botulinum antitoxin injection, neurotrophic therapy, nutrition supplementation, modulation and enhancement of cellular immune function, and systemic supportive care based on their condition. Prior to antitoxin administration, a skin test was performed. Patients with a negative test received intramuscular injections of 10 000 U of antitoxin serum every 12 hours, while those with a positive result underwent a desensitization protocol. The cessation criterion was significant improvement of toxic symptoms. Data collected included age, gender, region, time of presentation, injection location, brand and type of toxin, injection time, sites and dose of injection, time to onset of initial symptoms, main symptoms, skin test result for antitoxin, dosage of antitoxin administered, length of hospital stay, adverse reactions and prognosis. Data analysis was performed using GraphPad Prism Version 10.2.0.Results:A total of 179 patients were included, with 8 cases in 2023 and 171 cases in 2024. The majority were female (97.2%, 174 cases). The age range was 18-62 years, with a median age of 35 years; the highest proportion was in the 20-40 age group (71.5%, 128 cases). Patients were from 23 different provinces, autonomous regions, and municipalities directly under the central government in China. The injected product was mostly an unspecified brand of botulinum toxin (57.5%, 103 cases). Injections were primarily administered in non-medical institutions, with beauty salons or private studios accounting for 88.8% (159 cases). Injection sites included the platysma (92 cases), masseter muscle (82 cases), orbicularis oculi muscle (82 cases), frontalis muscle (67 cases), among others, with some patients receiving injections at multiple sites. 69 cases (38.5%) of patients were unaware of the injected dose; for the remaining cases, based on information provided, the injected doses were all within the safe range. The incubation period was mostly 1-7 days. The main symptoms included fatigue (171 cases), dysphagia (137 cases), dizziness (101 cases), blurred vision (76 cases), and difficulty opening eyes (66 cases). 176 patients received botulinum antitoxin treatment; 82 cases (46.6%) had a positive skin test and received desensitization injections, while 94 cases (53.4%) had a negative test. The total dosage of antitoxin used ranged from 10 000 U to 240 000 U. Three patients received only adjuvant therapy such as neurotrophic support. Adverse reactions during treatment primarily included induration at the injection site and serum sickness, all of which resolved after symptomatic treatment with antihistamines, steroids, etc. The hospital stay ranged from 1 to 24 d, with an average of 4.6 d. Upon discharge, symptoms in all patients had alleviated or resolved. At the 6-month follow-up after discharge, 14 patients were lost to follow-up; the remaining patients recovered well with no other complications.Conclusion:Poisoning incidents due to the illegal or improper use of botulinum toxin are increasing. Administration of botulinum antitoxin is an effective means to ameliorate intoxicating symptoms. Patients should seek timely medical intervention and receive antitoxin treatment as early as possible. Desensitization administration does not affect the efficacy of the antitoxin.