This paper discusses the pathogenesis and treatment strategies of skin cancer based on the theory of "spleen deficiency-sweat pore obstruction-toxin accumulation". It is believed that although the disease is located in the skin and body hair， it is not only the localized disorder but closely related to the imbalance of qi and blood of zang-fu （脏腑） organs. The core of the disease is the synergistic disorder of spleen， sweat pore， and skin and body hair. The disease progression follows a dynamic evolution from spleen deficiency with loss of nourishment， initial closure of sweat pore to binding of dampness and stasis with obstruction of sweat pore， and then to cancer toxin consolidation with damage to sweat pore. Based on this， three principles of building earth， opening sweat pore and attacking toxin are established. The method of fortifying spleen and raising the clear aims to consolidate the root and restore validity， with commonly used prescriptions including modifications of Buzhong Yiqi Decoction （补中益气汤）， Liujunzi Decoction （六君子汤） and Guipi Decoction （归脾汤）. The method of opening sweat pores with acrid-moistening medicinals is suggested when dredging and unblocking the sweat pore， commonly using acrid and warm dispersing medicinals， supplemented with herbs that nourish fluids and moisten dryness. The method of clearing heat and removing toxin is to break cancer toxin directly， and modifications of prescriptions such as Wuwei Xiaodu Beverage （五味消毒饮）， Xiaolei Pills （消瘰丸） and Xihuang Pills （犀黄丸） are commonly used. These approaches provide valuable ideas for the prevention and treatment of skin cancer with traditional Chinese medicine.

This paper discusses the pathogenesis and treatment strategies of skin cancer based on the theory of "spleen deficiency-sweat pore obstruction-toxin accumulation". It is believed that although the disease is located in the skin and body hair， it is not only the localized disorder but closely related to the imbalance of qi and blood of zang-fu （脏腑） organs. The core of the disease is the synergistic disorder of spleen， sweat pore， and skin and body hair. The disease progression follows a dynamic evolution from spleen deficiency with loss of nourishment， initial closure of sweat pore to binding of dampness and stasis with obstruction of sweat pore， and then to cancer toxin consolidation with damage to sweat pore. Based on this， three principles of building earth， opening sweat pore and attacking toxin are established. The method of fortifying spleen and raising the clear aims to consolidate the root and restore validity， with commonly used prescriptions including modifications of Buzhong Yiqi Decoction （补中益气汤）， Liujunzi Decoction （六君子汤） and Guipi Decoction （归脾汤）. The method of opening sweat pores with acrid-moistening medicinals is suggested when dredging and unblocking the sweat pore， commonly using acrid and warm dispersing medicinals， supplemented with herbs that nourish fluids and moisten dryness. The method of clearing heat and removing toxin is to break cancer toxin directly， and modifications of prescriptions such as Wuwei Xiaodu Beverage （五味消毒饮）， Xiaolei Pills （消瘰丸） and Xihuang Pills （犀黄丸） are commonly used. These approaches provide valuable ideas for the prevention and treatment of skin cancer with traditional Chinese medicine.

Objective:To investigate the effect of dulagopeptide on physical examination indexes,plasma glucose metabolism and islet function in type 2 diabetes mellitus(T2DM)patients with poorly controlled plasma glucose.Methods:135 T2DM patients with poorly controlled plasma glucose who were admitted in our hospital from January 2023 to July 2024 were selected.A prospective randomized controlled design was adopted,they were divided into control group 1(received treatment with sitagliptin,n=45),control group 2(received treatment with insulin glargine,n=45),and observation group(received treatment with dulaglutide,n=45)according to the random number table method.Physical examination indexes,plasma glucose indicators,islet function,and incidence of adverse reactions were compared among the three groups.Results:12 weeks after treatment,body mass index(BMI),waist circumference,fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),and postprandial 2-hour plasma glucose(2hPG)in the observation group were lower than those in control group 1 and control group 2(P＜0.05).12 weeks after treatment,the observation group had the highest HbA1c compliance rate,reaching 71.1％(P＜0.05).12 weeks after treatment,the fasting C-peptide(FC-P)and HOMA-islet(CP-DM)levels in the observation group were higher than those in control group 1 and control group 2(P＜0.05).Conclusion:Dulagopeptide can effectively improve physical examination indexes,plasma glucose indicators,and islet function in T2DM patients with poorly controlled plasma glucose.

Objective To analyze the epidemiological distribution,microbiological characteristics,drug-resistance status,and risk factors for mortality in adult intensive care unit(ICU)patients with Klebsiella pneumoniae infection.Methods This multi-center prospective cohort study included ICU patients with suspected infection from 67 hospitals across 16 Chinese provinces/municipalities between July 1,2021 and December 31,2022.Clinical data and microbiological results were collected,and patients were divided into survival and non-survival groups according to their survival status and drug-resistance situation.Risk factors for mortality and drug resistance in ICU patients with Klebsiella pneumonia infection were determined through univariate and multivariate logistic regression analyses.Results A total of 2964 ICU-infected patients were enrolled,with 12 175 microbial specimens submitted for testing.Among these,487 specimens tested positive for Klebsiella pneumoniae.Ultimately,314 patients with Klebsiella pneumoniae infection were identified,primarily from lung infections,with a drug-resistance rate of 78.3%.The in-hospital mortality rate of ICU patients infected with Klebsiella pneumoniae was 19.8%.Univariate and multivariate logistic regression analyses revealed that older age(P=0.027),high drug-resistance rate(P=0.028),and low clinical-effectiveness rate(P<0.001)were independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae.Drug-resistance analysis showed that,compared with non-resistant cases,ICU patients with drug-resistant Klebsiella pneumoniae infection had lower pathogen-clearance rates(P=0.003),clinical-effectiveness rates(P=0.004),and antibiotic-effectiveness rates(P<0.010),and higher mortality rates(P=0.006).Patients with Klebsiella pneumoniae abdominal infection(P=0.003)and urinary tract infection(P=0.007)had higher drug-resistance incidences.There were no statistically significant differences in clinical-effectiveness rate,Klebsiella pneumoniae clearance,drug-resistance incidence,mortality rate,or hospital-stay length between patients with lung infection and those with non-lung infection of Klebsiella pneumoniae(P>0.05).Compared with patients with non-bloodstream infection,patients with bloodstream infection of Klebsiella pneumoniae had lower clinical-effectiveness rates(P=0.027)and higher mortality rates(P=0.021).Conclusions Older age,high drug-resistance rate,and low clinical-effectiveness rate are independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae.ICU patients with bloodstream infection of Klebsiella pneumoniae may have lower clinical-effectiveness rates and higher mortality rates.ICU patients with abdominal and urinary tract infections caused by Klebsiella pneumoniae are more likely to develop drug resistance.

Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

Objective To analyze the distribution characteristics of the single nucleotide polymorphism (SNP) site rs76206423 in the promoter region of the interleukin-2 receptor (IL-2R) β gene among Han males in a high radiation background area (HBRA) in Yangjiang City. Methods A total of 48 male participants from Tangkou Town, Yangxi County, Yangjiang City (HBRA group), and 51 male participants from Hengpo Town, Enping City (control group) were selected as the research subjects using the random number table method. Peripheral venous blood samples of participants from both groups were collected, and genomic DNA was extracted. The genotyping and allele frequency distribution of the rs76206423 (A/G) site in the IL-2R β promoter region was detected among the participants in both groups using the SNP detection method. The difference of allele frequencies between population in HBRA group and five area of East Asia, South Asia, Africa, Europe, and the Americas published in the Human Genome Project database from National Center for Biotechnology Information were analyzed. Results The allele frequencies of rs76206423 of population in both groups conformed to Hardy-Weinberg equilibrium (P>0.05). In the HBRA group, the AA genotype was predominant (64.6%), while the AG genotype was the most common in the control group (51.0%), with a significant difference (P<0.05). Population in both groups showed a predominance of the variant allele A (78.1% and 72.5%, respectively), with no significant difference (P>0.05). The frequency of the G allele of rs76206423 in the population in HBRA group was higher than those in South Asian, African, European, and American populations (all P<0.01), but showed no significant difference compared with East Asian populations (P>0.05). Conclusion In the Han male population from the HBRA in Yangjiang City, the rs76206423 site in the IL-2R β gene promoter region is predominantly composed of the wild-type A allele and AA genotype, indicating genetic stability and a relatively high degree of variation at this locus.

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective To summarize the best evidence for the evaluation,implementation,and assess-ment of early rehabilitation exercise for patients with severe traumatic brain injury,provide evidence-based support for clinical nursing and reduce disability and mortality rates.Methods Relevant evidence on early re-habilitation exercise of patients with severe traumatic brain injury from 14 databases or official websites inclu-ding BMJ Best Practice,UpToDate,BMJ Clinical Evidence,the official website of the World Health Organiza-tion(WHO),International Guidelines Collaboration Network(GIN),National Guidelines Library(NGC)in the United States,Scottish Inter Collegiate Guidelines Network(SIGN),JBI Evidence Based Healthcare Knowledge Base,Cochrane Library,PubMed,Embase,Cumulative Index of Nursing and Allied Health Litera-ture(CINAHL),China National Knowledge Infrastructure(CNKI),and Wanfang were retrieved,the latest clinical decisions,guidelines,evidence summaries,expert consensus,systematic reviews,clinical practices,and review results were integrated,the best evidence were extracted,and quality evaluation and classification were conducted.Results A total of 15 articles were included,summarizing 26 best pieces of evidence from six as-pects:early rehabilitation exercise assessment,early awakening rehabilitation treatment therapy,early respira-tory and airway management,early limb activity and muscle joint rehabilitation training,early bladder function training,and early nutritional management.Conclusion This study integrates the best evidence of early reha-bilitation exercise for patients with severe traumatic brain injury,providing evidence-based support for further clinical nursing practice,promoting the rehabilitation process of patients with traumatic brain injury,and im-proving their quality of life.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.