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.

With the emergence of high-throughput technology and massive toxicology data,toxicology research has entered the era of big data.How to efficiently integrate existingtoxicological data,clarify the toxic effects of chemicals,and use these patterns to providenew information,in order to achieve effi-cient prediction of the toxicity of new chemicalsubstances,is one of the cutting-edge issues in toxicology.In view of the high cost,low throughput and difficulty in revealing the mechanism information of tradi-tional chemical toxicity testing methods,high throughput prediction models are urgently needed.Machine learning methods have been applied to toxicity testing,such as supervised learning models,unsupervised learning models,deep learning models,reinforcement learning models,and transfer learning models.Chemical characteristic data commonly used in machine learning models include chemical structure data,text data,toxicological genome data and image data.There is huge potential for applying machine learning to toxicity testing and machine learning methods have made some prog-ress.However,current research focuses on the processing of data and development of models,which has failed to produce a widely used and accepted method.In addition,the prediction accuracy of machine learning models is not only dependent on algorithms,but also affected by data quality,and the mutual promotion and development of algorithms and data quality remains a big challenge.In short,data processing and model construction in the field of toxicology require interdisciplinary cooperation and technological innovation.With the increasing perfection of toxicology databases and the continuous optimization of various model algorithms,the toxicity prediction of new chemicals based on machine learning models will become increasingly efficient and accurate,playing an important role in ensuring human health and environmental safety.

Objective To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis,by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis.Methods Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected,and the samples of necrotic osteonecrosis from chronic osteomyelitis(necrotic group),and normal bone tissue(control group)were collected.Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform,and the gene expression in bone tissue was calculated by FPKM.The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group.Genes were enriched by GO and KEGG.MAP3K7 and NFATC1 were selected as differential targets in the verification experiments,by using rat osteomyelitis animal model and im-munohistochemical analysis.Results A total of 5548 differentially expressed genes were obtained by high throughput sequenc-ing by comparing the necrotic group and control group,including 2701 up-regulated and 2847 down-regulated genes.The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened,the common genes expressed in both MAPK and osteoclast differentiation pathway were(inhibitor of nuclear factor κ subunit Beta,IκBKβ),(mitogen-activated protein ki-nase 7,MAP3K7),(nuclear factor of activated t cells 1,NFATC1)and(nuclear factor Kappa B subunit 2,NFκB2).In rat os-teomyelitis model,MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue.Conclusion Based on the transcriptome analysis,the MAPK signaling and osteoclast differentiation pathways were closely related to chronic os-teomyelitis,and the key genes IκBKβ,MAP3K7,NFATC1,NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Objective:To explore the clinical efficacy of immunoadsorption in highly sensitized kidney transplant (KT) candidates.Methods:From September 2019 to April 2023, the relevant clinical data were retrospectively reviewed for 26 highly sensitized KT recipients. Protein A immunoadsorption desensitization therapy was offered after KT. The effect of immunosorbent on reducing anti-human leukocyte antigen (HLA) antibodies was summarized. And operative success rate and postoperative complication incidence were calculated.Results:The mean number of treatment session was (10.76±5.53). The highest level of HLA-Ⅰ antibody mean fluorescence intensity (MFI) dropped from (17 921±4 442) to (7 333±6 434) with a decline of 59% and HLA-Ⅱ antibody MFI decreased from (21 135±5 245) to (10 989±7 627) with a decline of 48%. The differences were statistically significant (both P<0.001). All kidneys were harvested from cadavers. The complications were acute antibody mediated rejection (7 cases), perioperative pulmonary infection (3 cases) and myelosuppression (2 cases). The average follow-up period was (30.8±12.6) month. The graft survival rate was 88.5% (23/26) and the recipient survival rate 100% (26/26) . Conclusions:Immunoadsorption therapy can effectively reduce HLA antibody in highly sensitized KT candidates, thereby increasing the probability of successful KT. In terms of safety, immunosorbent therapy may boost the potential risks of infection and myelosuppression. It requires heightened attention.

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Objective To investigate the clinical efficacy of modified Banxia Houpu Decoction plus Deanxit for the treatment of cancer-related depression(CRD)of phlegm blended with qi type.Methods Sixty-four CRD patients with phlegm blended with qi type were randomly divided into the treatment group and the control group,with 32 patients in each group.The control group was given oral use of Deanxit,and the treatment group was treated with modified Banxia Houpu Decoction plus Deanxit orally.The course of treatment covered 4 weeks.The changes of Karnofsky Performance Status(KPS)scores,self-rating depression scale(SDS)scores,and traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before and after the treatment.Moreover,the efficacy for improving KPS scores and TCM syndrome efficacy in the two groups were also evaluated.Results(1)After 4 weeks of treatment,the total effective rate for improving KPS scores in the treatment group was 90.63%(29/32),and that in the control group was 78.13%(25/32).The intergroup comparison showed that the efficacy for improving KPS scores in the treatment group was significantly superior to that in the control group(P＜0.01).(2)In terms of the efficacy of TCM syndromes,after 4 weeks of treatment,the total effective rate for improving TCM syndrome scores in the treatment group was 87.50%(28/32),and that in the control group was 40.63%(13/32),and the efficacy of TCM syndromes in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the KPS scores in the treatment group were significantly increased compared with those before treatment(P＜0.05),and the KPS scores in the control group tended to increase compared with those before treatment,but the difference was not statistically significant(P＞0.05).The intergroup comparison showed that the effect on increasing KPS scores in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the SDS scores in the two groups were lower than those before treatment(P＜0.05),and the effect on lowering SDS scores in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the TCM syndrome scores of the two groups were lower than those before treatment(P＜0.05),and the effect on lowering TCM syndrome scores in the treatment group was significantly superior to that in the control group(P＜0.05).Conclusion Modified Banxia Houpu Decoction plus Deanxit exerts certain effect for the treatment of CRD of phlegm blended with qi type.The combined therapy can effectively improve the depression mood and quality of life of the patients,and its efficacy is superior to that of Deanxit alone.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

The identification of the components absorbed in serum of platycosides in total saponins fraction of Platycodonis Radix is great significance, but there are still great challenges. In this study, 8 types of 44 primordial components from Platycodon saponins were firstly identified using the ultra-performance liquid chromatography-linear ion trap electrostatic field orbitrap high resolution mass spectrometry (UPLC-LTQ-Orbitrap-MS) equipped with the software of Compound Discoverer 3.2 and Trace finder 2.1. Then, the platycosides and their deglycosylated metabolites were used as the template molecules to construct the intestinal microbiota mediated method to identify the primary components and the prototypes in serum. As results, 57 components originating from 44 prototypes of platycosides were identified from drug-containing plasma. Those compounds consist of 12 prototypes of platycosides and 45 metabolites, while the prototypes in serum are also deglycosylated metabolites of other platycosides. The results showed that the intestinal microbiota mediated method could be applied to identify the metabolites of platycosides in total saponins fraction of Platycodonis Radix; and reveal the potential existing forms of prototypes of platycosides in plasma; In addition, it could clearly illustrate the one to many and many to one network of the prototypes and metabolites of platycosides. All animal protocols were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (No.JZLLSC-202100322).