Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC₈₀ = 32 μg·mL^-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

We aimed to identify the infectious source of a case of melioidosis,to provide evidence for the prevention and control of melioidosis in Shanxi Province,China.The patient developed repeated fever,fatigue,diarrhea,and other symptoms after being caught in the rain while traveling in Hainan Province.The blood culture was positive,and the bacterial strain was i-dentified as Burkholderia thayensis and sent to the provincial Center for Disease Control and Prevention for further evaluation.MALDI-TOF MS and biochemical identification were used to identify the strain,whole genome sequencing was performed after nucleic acid extraction,MLST type and drug-resistance genes were analyzed,and a phylogenetic tree was constructed.The iso-lated strain was identified as Burkholderia pseudomallei by MALDI-TOF MS and biochemistry,and the MLST type was 366.The whole gene sequencing analysis indicated a close evolutionary relationship with the three isolates in Hainan Province,with high homology.This case of melioidosis was indeed imported from Hainan Province,according to molecular tracing analysis and epidemiological investigation,thus suggesting that medical institutions and disease control departments should strengthen understanding of melioidosis,and improve the diagnosis and treatment ability.

Cardiovascular and cerebrovascular diseases, usually result from atherosclerosis, has the highest mortality rate globally. Lipid metabolism disorder is the main cause of atherosclerotic cardiovascular and cerebrovascular diseases, which not only lead to acute diseases such as myocardial infarction, stroke, acute pancreatitis, but also chronic kidney disease. In recent years, the advancement of gene therapy technologies has provided novel means for lipid metabolism study, and has also made it possible to cure patients with congenital lipid metabolism abnormalities. Adeno-associatd virus has a wide host range, high safety, low immunogenicity, and especially the ability of long-term stable expression in vivo, making it the preferred delivery tool for gene therapy of monogenic genetic diseases. Alipogene triprivec, also known as Glybera, was approved by the European Medicines Agency in 2012. It is the first gene therapy drug that uses recombinant AAV1 vector to directly deliver a highly active LPL protein S447X mutant to muscle cells for the treatment of patients with hereditary LPL deficiency. To enhance the targeted transduction efficiency of AAV carriers, recombinantAAV8.TBG.hLDLR utilizes the tissue tropsim of AAV8 to liver, meanwhile utilizes a liver specific thyroxine binding globulin promoter to control gene transcription, thereby achieving liver cell specific high expressionof human low-density lipoprotein receptors (LDLR). In patients with familial hypercholesterolemia,AAV8.TBG.hLDLR treatment effectively lower the level of plasma LDL for a long time, thus preventing the occurrence of atherosclerosis.Proprotein convert subunit kexin 9 (PCSK9) is secreted by liver cells. PCSK9 binds and transports LDLR to lysosomes for degradation, preventing the circulation and regeneration of LDLR, leading to accelerated degradation of LDLR and finally resulting in the accumulation of low-density lipoprotein cholesterol in plasma. Using AAV to deliver Cas9 of Staphylococcus aureus and gRNA targeting the Pcsk9 gene can knock out Pcsk9 in mouse liver, leading to a long-term significant decrease in plasma cholesterol levels in mice. Hepatocyte specific angiopoietin related protein 3 (Angptl3) is an endogenous inhibitor of LPL. Using the AAV9 mediated AncBE4max system and the dCas9 mediated single base gene editing system to introduce early termination codons, the knockout of Angptal3 in liver cells was achieved with an average knockout efficiency of 63.3%. After 2-4 weeks of administration in mice, the Angptl3 protein was completely undetectable in the peripheral blood, and serum triglycerides and total cholesterol decreased by 58% and 61%, respectively. Ring finger containing protein 130 (RNF130) is an E3 ubiquitin ligase. Research has shown that overexpression of RNF130 using AAV2/8 leads to ubiquitination degradation and redistribution of LDLR on the cell membrane, significantly reducing LDLR expression on liver cells and increasing plasma LDLC levels, while knocking out Rnf130 gene using the AAV-CRISPR system results in the opposite effect. This AAV mediated RNF130 function study proves that RNF130 is a posttranslational regulatory protein of LDLR and plays an important role in the regulation of serum LDLC. As mentioned above, recently, various lipid-lowering gene therapy drugs carried by different serotypes of adeno-associated virus have been applied in clinic or are undergoing clinical trials, and adeno-associated virus has emerging to be an important tool for lipid metabolism research.This article reviews the new progress of adeno-associated virus vectors in lipid metabolism study and lipid-lowering gene therapy.

Objective To explore the clinical characteristics and treatment scheme of patients with spinal infection caused by Prevotella intermedia(P.intermedia).Methods Clinical diagnosis and treatment processes of a patient with spinal infection caused by P.intermedia admitted to the spinal surgery department of a hospital were summa-rized,and relevant literature was retrieved from database for reviewing.Results The patient,a 50 year old male,was admitted to the hospital due to"lumbago pain complicated with pain in double lower extremities for 2 months".The lesion tissue was taken for metagenomic next-generation sequencing(mNGS)detection,which detected P.in-termedia,and the patient was diagnosed with P.intermedia spondylitis.After treatments with open lesion clea-rance,tube rinsing+autologous bone transplantation fusion internal fixation,intravenous drip of ceftriaxone sodium and metronidazole,as well as metronidazole rinsing,infection was under control.A total of 16 available papers were retrieved,together with this case,a total of 17 patients were included,with 7 males and 10 females.The main risk factors were diabetes and history of corticosteroid use(35.3％).The most common invasion sites were lumbar ver-tebra(n=12)and thoracic vertebra(n=6).13 cases were positive for pathogen culture,3 cases were positive for molecular detection,and 1 case was positive for staining microscopy.17 patients received anti-anaerobic bacteria treatment,with 14 cases receiving combined surgical treatment.One case died,with a mortality of 5.9％;5 cases had partial neurological impairment,with a disability rate of 29.4％.The survival rate of patients who received treatment of anti-anaerobic bacteria combined with surgery was 92.8％,3 patients only with anti-anaerobic bacteria treatment but without surgery were all cured.Conclusion P.intermedia is an opportunistic pathogeanic bacteria which often causes infection in immunocomprised individuals and is prone to be misdiagnosed.It is recommended to perform mNGS detection to identify the pathogen as early as possible and seize the opportunity for treatment to reduce mortality.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective To observe the effect of hyolroxylsafflor(HSYA)on cyclooxygenase-2(COX-2)/prostaglandin E2(PGE2)signaling pathway,and to investigate the protective effect and mechanism of HSYA on cerebral ischemia-reperfusion injury(CIRI).Methods Totally 90 SD male rats were randomly divided into sham-operated group(S group),operation group(CIRI group),HSYA group and celecoxib group(C group),HSYA group subdivided into HSYA low dose group(HSYA-L group),HSYA medium dose group(HSYA-M group)and HSYA high dose group(HSYA-H group),15 rats in each group.CIRI model was prepared by thread embolism method.The rats in each group were given intraperitoneal injection 30 minutes before operation.HSYA groups were given HSYA 10 mg/kg,15 mg/kg,25 mg/kg respectirely;C group was given celecoxib 40 mg/kg;S group and CIRI group were given the same amount of normal saline.Neurofunctional scores of each group of rats were performed immediately after recovery from modeling,cerebral infarction volume was measured 24 hours after reperfusion;At the same time,neuronal injury was observed by Nissl staining,the changes of COX-2 mRNA and protein were detected by Real-time PCR and Western blotting,and the changes of PGE2,tumor necrosis factor α(TNF-α)and interleukin(IL)-1β were detected by ELISA.Results Compared with the S group,in the CIRI group,neurofunctional scores increased dramatically(P＜0.05),the volume of cerebral infarction increased dramatically(P＜0.05),the damage of neurons increased and the number of neurons decreased dramatically(P＜0.05),the expressions of COX-2 mRNA and protein increased dramatically(P＜0.05),meanwhile the expressions of PGE2,TNF-α and IL-1β were also found dramatically increased(P＜0.05);Compared with the CIRI group,in the HSYA group and C group,neurofunctional scores decreased dramatically(P＜0.05),the volume of cerebral infarction was reduced dramatically(P＜0.05),the damage of neurons decreased and the number of neurons increased dramatically(P＜0.05),the expressions of COX-2 mRNA and protein,PGE2,TNF-α and IL-1β decreased dramatically(P＜0.05).The differences between HSYA groups and both HSYA-L group and HSYA-M group compared with the C group were obvious(P＜0.05),while no obvious differences were found in HSYA-H group compared with the C group(P＞0.05).Conclusion HSYA alleviates reperfusion injury in ischemic stroke may be related to the inhibition of COX-2/PGE2 signaling pathway.