As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

Objective To analyze the changes in optical coherence tomography angiography (OCTA) parameters in patients with essential hypertension，and to explore the effect of blood pressure on OCTA parameters. Methods A total of 164 patients with essential hypertension were selected and divided into controlled blood pressure group (n=92) and uncontrolled blood pressure group (n=72). OCTA examination was performed on the optic disc and macula of all patients, and the right eyes were selected for analysis. Results There were no significant differences in retinal nerve fiber layer (RNFL) thickness, radial peripapillary capillary (RPC) total vascular density, RPC total small vessel density, perifovea superficial capillary plexus (SCP) vascular density, and perifovea deep capillary plexus (DCP) vascular density between the two groups of patients. There were no significant differences in foveal avascular zone (FAZ) area, FAZ diameter, and fovea retinal thickness between the two groups of patients. The density of the parafovea SCP, parafovea DCP, and fractal dimension (FD) in the uncontrolled blood pressure group were significantly lower than those in the controlled blood pressure group (P＜0.05). Multiple linear regression analysis showed that elevation of blood pressure was a independently related factor of reduced parafovea DCP density (P＝0.026), while there was no correlation between the uncontrolled blood pressure and parafovea SCP density and FD level. Conclusions The blood pressure level is correlated with the parafovea DCP density, while has no correlation with other OCTA parameters in hypertension patients.

Objective To explore the roles of transcription factor E26 transformation-specific 1(ETS1)and F-box protein 45(FBXO45)in invasion and metastasis in hepatocellular carcinoma cells and the potential molecular mechanism.Methods Jaspar,hTFtarget and Cistrome transcription factor database prediction websites were used to predict the transcription factors of FBXO45.According to the intersection of the predicted results of each database,the expression of FBXO45 was detected after the candidate transcription factors were knockdown in HCCLM3 and Huh7 liver cancer cells,respectively.The most significant influence on FBXO45 expression was selected for further analysis,and chromatin immunoprecipitation assay(ChIP)was used to verify the binding to the FBXO45 promoter.Finally,the potential transcription factor of FBXO45 was identified.The effect of ETS1 overexpression on invasion and migration in HCCLM3 and Huh7 cells was detected by Transwell assay,and the expression levels of epithelial-mesenchymal transition(EMT)pathway proteins were detected by Western blot assay.The effects of FBXO45 knockdown on the invasion and migration under the condition of overexpression of ETS1 were also studied.Results Intersection of FBXO45 transcription factors identified 3 candidate transcription factors,ETS1,SPI1 and YY1.When the 3 transcription factors were knocked down in HCCLM3 and Huh7 cells,respectively,ETS1 knockdown significantly reduced the expression of FBXO45.According to the analysis of The Cancer Genome Atlas(TCGA)data and the Gene Expression Omnibus(GEO)data,the expression levels of ETS1 and FBXO45 were significantly positively correlated(R=0.31,P<0.000 1;R=0.40,P=0.021 9).ChIP suggested that ETS1 could specifically bind to FBXO45 promoter sequence to regulate its expression,confirming that ETS1 was a potential transcription factor of FBXO45.After overexpression of ETS1 in HCCLM3 and Huh7 cells,the invasion and migration abilities of cells were significantly enhanced,and the expression of N-cadherin and Snail was up-regulated(P<0.01).In addition,in the case of ETS1 overexpression,FBXO45 knockdown significantly inhibited the invasion and migration(P<0.01).Conclusion ETS1 activates the transcription of FBXO45 and leads its high expression,which enhances the invasion and migration of HCC cells via EMT pathway and promotes the progression of hepatocellular carcinoma.

Objective:To investigate differentially expressed lipid molecules and their associated metabolic pathways in lung tissue using lipidomic analysis in a rat model of acute lung injury (ALI).Methods:An ALI rat model was established via intratracheal instillation of lipopolysaccharide (LPS). Twenty rats were randomly allocated into an ALI group and a control group ( n = 10 per group). The left lung was subjected to histopathological evaluation, while the right lung underwent untargeted lipidomics analysis. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for lipid profiling. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to assess intergroup differences and determine variable importance in projection (VIP) scores. Differential lipids were screened based on VIP and fold change.Lipid identification and metabolic pathway analysis were conducted using MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results:Among 1 022 detected lipid molecules, 47 were differentially expressed (VIP > 1, FC > 2.0 or < 0.5, P< 0.05). Subsequent analysis identified 12 structurally annotated lipids ( P < 0.05), predominantly enriched in glycerophospholipid metabolism, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Notably, phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) exhibited significant alterations in the ALI group. Conclusions:The ALI model demonstrated substantial dysregulation of lipid metabolism, particularly involving PCs and LPCs, with prominent perturbations in glycerophospholipid metabolism. This provides a scienctific basis for indepth research on the pathogenesis mechanism of ALI/acute respiratory distress syndrome (ARDS) .

Objective To investigate the mechanism of Gentianopsis paludosa xanthone(GPX)combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors.Methods Ninety rats were divided into the normal group,the model group[drinking sodium dextran sulfate(DSS)for 3 days]and the intervention group by random number table method.The model group was subdivided into the inflammatory stage group,the pre-inflammatory cancer group(DMH injection for 4 weeks),the intermediate inflammatory cancer group(DMH injection for 13 weeks)and the advanced inflammatory cancer group(DMH injection for 21 weeks).The administration group was subdivided into the groups(after the first day of drinking DSS,drugs for each group were given by gavage once a day for 8 weeks)on the basis of the advanced inflammatory cancer group,including the GPX group(GPX 69.3 mg/kg),the probiotic group,the combined group(GPX+probiotics 400 mg/kg)and the thalidomide group(thalidomide 13.5 mg/kg).The disease activity index(DAI),colon length and wet mass index were compared between all groups.Characteristics of colon tumors were observed,and pathological changes of colon were observed by HE staining.The expression levels of transforming growth factor(TGF)-β1,Smad4,Smad7,interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by Western blot assay and enzyme-linked immunosorbent assay,respectively.Results Compared with the advanced inflammatory cancer group,the administration groups showed an increase in colon length,the expression levels of TGF-β1 and Smad4 protein,a decrease in colon wall thickness,wet mass index,maximum tumor diameter,the levels of Smad7,IL-6,TNF-α,and DAI score decreased in the GPX group and the combined group(P＜0.05).The structure and morphology of intestinal mucosa were improved in the GPX group,the probiotic group and the combination group,and the structure of colonic crypt and goblet cell number were increased.Compared with the probiotic group and the GPX group,the colon wall thickness,colon wet mass index and tumor number were decreased,the protein expression levels of TGF-β1 and Smad4 were increased,and levels of IL-6 and TNF-α were decreased in the combination group(P＜0.05).Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor,and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.

Objective:To explore the predictive value of myocardial work echocardiography on short-term mortality of patients with sepsis and septic shock(SSS).Methods:Patients who hospitalized in the ICU department of the Affiliated Lianyungang Hospital of Xuzhou Medical University from September 2022 to December 2023 were selected through prospective research.These patients,who need use vasopressor drugs,appeared clinical symptoms of sepsis and occurred septic shock.A total of 33 adult patients were continuously enrolled.According to whether patients with SSS died or survived within 28 days,they were divided into a survival group(23 cases)and a non-survival group(10 cases).The changes of myocardial function,serum lactic acid level,white blood cell(WBC)count,c-reactive protein(CRP)and other indexes were compared and assessed between the two groups after admission,and the predictive value of these parameters on short-term mortality in patients with sepsis and septic shock was investigated.Results:On the 3rd day after admission of patients with sepsis and septic shock,the heart rate,serum lactic acid level,white blood cell(WBC)count,global wasted work(GWW),and high-sensitivity cardiac troponin Ⅰ(hs-cTnⅠ)of non-survival group significantly higher than those of survival group(Z=-2.668,-2.550,-2.338,-2.175,-2.998,P＜0.05),and the global work efficiency(GWE)of non-survival group significantly decreased(Z=-2.311,P＜0.05).On the 5th day after admission,the heart rate,serum lactic acid level,WBC count,c-reactive protein(CRP)level of non-survival group significantly increased(Z=-3.073,-2.494,-3.408,-2.999,P＜0.05),and the pH value and global work index(GWI)of that significantly decreased(Z=-1.997,-2.546,P＜0.05).Serum lactic acid on the 3rd day and global work index on the 5th day were respectively independent risk factors for 28-day mortality in SSS patients after admission(OR=5.120,0.997,P＜0.05).On the 5rd GwI and serum lactic acid on the 3rd have similar values in predicting 28-day mortality in SSS patients[area under curve(AUC)value of receiver operating characteristics(ROC)curve of them were respectively 0.784 and 0.801,P＞0.05].Conclusion:Myocardial work echocardiography is helpful to identify the high risk of short-term death of SSS patients.Serum lactic acid of the 3rd day and global work index of the 5th day after admission are respectively independent risk factors for 28-day death in SSS patients.

Objective To investigate the expression of hepatoma-derived growth factor(HDGF)in hepatocellular carcinoma(HCC)and its effects on DNA damage,proliferation,migration,epithelial mesenchymal transition(EMT),and expression of osteoprotegerin(OPG)in HCC cells.Methods GEO database was analyzed to obtain the expression features of differential expressed mRNAs in liver tumors between HCC patients with bone metastasis and those without,and then HDGF was found as the most significantly differentially expressed gene.The mRNA expression of HDGF was verified in the HCC cells with varying metastatic capabilities by qRT-PCR.DNA damage levels in different groups of liver cancer cells were analyzed through y-H2AX immunofluorescence assay.The effects of HDGF on cell proliferation and migration were detected with CCK-8 assay,colony formation assay,and Transwell migration assay.Western blotting was employed to measure the expression of EMT-related proteins Vimentin and E-cadherin in HCC cells with various capacities of bone metastasis.Then qRT-PCR and Western blotting were performed to determine the differential expression of OPG in various groups of liver cancer cells.Results HDGF was highly expressed in HCC tissues with bone metastasis and in high-metastatic HCC cell lines.High expression of HDGF inhibited DNA damage repair.HDGF promoted the proliferation and migration of HCC cell lines.HDGF up-regulated the protein expression level of Vimentin while down-regulated that of E-cadherin(both P＜0.05),and overexpression of HDGF down-regulated the expression of OPG.Conclusion HDGF is highly expressed in bone metastatic hepatocellular tumors and may promote bone metastasis by facilitating EMT,migration,and proliferation.

Objective:To analyze the biochemical failure rate and its predictive factors after radical prostatectomy (RP) in patients with high-risk localized prostate cancer.Methods:The data of 166 patients with high-risk localized prostate cancer who underwent RP surgery in Peking university cancer hospital from January 2015 to November 2021 were retrospectively reviewed. The average age was 65.4±6.2 years old, and the average body mass index (BMI) was 24.86±3.23 kg/m 2. The median prostate-specific antigen (PSA) was 19.84 (10.98, 44.47) ng/ml, PSA density was 0.68 (0.34, 1.32)ng/ml 2, and prostate volume was 31.20 (25.58, 40.23) ml. Biopsy pathology Gleason score according to the International society of Urological Pathology(ISUP) grade group: 18 cases of group 1, 33 cases of group 2, 30 cases of group 3, 51 cases of group 4, and 33 cases of group 5, 1 case was unknown. The percentage of puncture positive needles was (55.4±25.7)%, and the largest linear length of positive lesions was 80.0% (60.0%, 90.0%). Preoperative clinical stage : 14 cases in ≤T 2b stage, 117 cases in T 2c stage, 13 cases in T 3a stage and 22 cases in ≥T 3b stage; 157 cases in N 0 stage, 9 cases in N 1 stage. One hundred and three patients (62.0%) were assessed by traditional imaging and 63(38.0%) were assessed by PSMA PET-CT. The patients underwent laparoscopic radical prostatectomy. 64 patients (38.6%) received neoadjuvant therapy, including 37 received neoadjuvant therapy for 1-3 months, 23 for 4-6 months and 4 for over 6 months. The postoperative pathological characteristics, treatment and prognosis of the patients were analyzed. The primary endpoint was biochemical failure, including biochemical persistence(BCP, defined as PSA≥0.1ng/ml at 4-6 weeks after operation, and confirmed by re-examination at least 1 week interval) and biochemical recurrence(BCR, PSA falling below 0.1ng/ml after operation and then rising ≥0.2 ng/ml without adjuvant therapy or after the end of adjuvant treatment). Results:Compared with preoperative clinicopathological characteristics, 48(28.9%) cases had postoperative pathological ISUP upgrade, 98 (59.0%)cases had T stage upgrade, and 13 (7.8%) cases had N stage upgrade. The rate of positive margins was 53%, and apex margin was the most common positive site (65.9%). The postoperative PSA in 114 patients (68.7%) decreased to less than 0.1ng/ml, of which 74 patients didn't receive the therapy and 40 patients received adjuvant therapy. 52 patients (31.3%) had postoperative PSA more than 0.1ng/ml and among them, 51 cases received salvage treatment. 5 patients (3.0%) underwent PSA progression during adjuvant or salvage endocrine therapy and were considered to have castration resistance. After a median follow-up time of 25.5 (12.0, 40.0) months, 78 patients (48.4%, 78/161) experienced biochemical failure, including 49 BCP and 29 BCR, the median time of biochemical failure was 30.0 (95% CI 14.5-45.5) months. Adjuvant therapy could reduce the rate of BCR (31.1% and 15.8%, P=0.08). Baseline PSA, PSA density, proportion of pathological ISUP ≥4, proportion of pathological T stage ≥T 3a, adjuvant therapy, and positive surgical margins were significantly associated with biochemical failure ( P=0.034, 0.002, 0.004, 0.025, <0.001and 0.047). Multivariate Cox regression analysis showed that adjuvant therapy ( P<0.001, OR=0.12), PSA density ( P=0.03, OR=1.19) and positive surgical margins ( P=0.034, OR=1.80) were independent factors for biochemical failure. Conclusions:Patients with high-risk localized prostate cancer have a high rate of biochemical failure after RP and need to receive RP-based multimodal therapy. Adjuvant therapy, PSA density and positive surgical margins are independent factors associated with postoperative biochemical failure.

Objective:To explore the cause of death of 2 suspected Yunnan sudden unexplained death (YNSUD) cases in Dayao County, Yunnan Province.Methods:The field epidemiological investigation and autopsy of 2 cases of YNSUD in Dayao County from June 15 to 20, 2020 were conducted; and blood and tissue samples were collected for qualitative analysis of common poisons and drugs.Results:The areas where the two cases were located were all seriously ill villages with a history of YNSUD, and the time of death occurred in the onset season of YNSUD. There was no blood relationship between the 2 cases, no obvious abnormal symptoms before death, no special diet, no history of exposure to pesticides and other toxic chemicals, and the test results of common poisons were all negative. Autopsy pathological examination results showed that case 1 died of acute cardiac dysfunction caused by sudden acute myocardial infarction of coronary heart disease, and case 2 died of central respiratory and circulatory failure caused by spontaneous subarachnoid hemorrhage.Conclusions:The two cases are excluded from YNSUD through autopsy, and the cause of death is determined. It is suggested that emergency response should be taken as soon as possible for YNSUD cases, and autopsy should be actively carried out to clarify the cause of death from a pathological point of view.