The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

Objective To investigate the effects of dienogest on pain relief and inflammation in endometriosis(EMs),as well as its impact on the brain-derived neurotrophic factor(BDNF)/tropo-myosin receptor kinase B(TrkB)and nuclear factor kappa-B(NF-κB)/NOD-like receptor protein 3(NLRP3)inflammatory pathways.Methods An allograft method was used to establish an EMs rat model.The rats were randomly divided into sham-operated group(n=16),model group(n=16),low-dose dienogest group(n=16),medium-dose dienogest group(n=16)and high-dose dienogest group(n=16).After 7 days of treatment,the implantation volume and writhing response frequency were recorded.Enzyme-linked immunosorbent assay(ELISA),reverse transcription-polymerase chain reaction and Western blotting were employed to measure the expression levels of vascular endothelial growth factor(VEGF),inducible nitric oxide synthase(iNOS),interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α in the EMs rat models.Serum levels of BDNF,TrkB,NF-κB and NLRP3 were detected.Results Compared with model group,dinorgestrel significantly reduced ectopic endo-metrial volume and torsion response of EMs(P＜0.05).Compared with model group,dinorgestrel significantly decreased the expression of VEGF,iNOS,IL6,IL-1 β and TNF-α in EMs model(P＜0.05).In addition,compared with model group,dienogest significantly decreased the expressions of BDNF,TrkB,NF-κB and NLRP3 in ectopic endometrium(P＜0.05).Conclusion Dinorgestrel can relieve EMS-related dysmenorrhea and inflammation,and its mechanism of action may be partly mediated by BDNF/TrkB pathway and NF-κB/NLRP3 pathway.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

The original version of this article unfortunately contained some mistakes.

Objective To explore the effect of specific labeling method in improving the mixed placing of medical waste in neonatal intensive care unit(NICU).Methods Medical waste classification of 34 trash cans in the NICU of a hospital between July and December 2014 were investigated,July-September was pre-implementation phase of spe-cific labeling,October-December was post-implementation phase,mixed placing of medical waste between pre-and post-implementation phase was compared.Results A total of 504 cases of medical waste classification in NICU were investigated,252 cases respectively in pre-and post-implementation phase,74 cases of mixed placing were found. Mixed placing rates before implementing specific labeling was higher than after implementing (25.40%[64/252]vs 3.97%[10/252],χ2 =46.187,P <0.001 );before implementing specific labeling,57 cases of infectious waste and non-infectious waste were mixed placing,after implementing specific labeling,only 8 cases of infectious waste and non-infectious waste were mixed placing.Mixed placing were mainly performed by trainees for in-service training and interns,accounting for 39.06% before implementing and 50.00% after implementing.Conclusion The specific labeling for standardizing and managing of medical waste can improve the classification of medical waste in NICU, significantly improve the compliance of all kinds of health care workers to the standard handling of medical waste.

This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was
12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .