ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

BACKGROUND:Studies demonstrated that miR-135a-5p was highly expressed in mouse embryonic palatal mesenchymal cells with cleft palate induced by dexamethasone.The primary cilium and its mediated Shh signaling pathway were involved in the autophagy of mouse embryonic palatal mesenchymal cells.It is speculated that miR-135a-5p may regulate autophagy in mouse embryonic palatal mesenchymal cells through primary cilia and its mediated Shh signaling pathway. OBJECTIVE:To investigate the regulatory effect of miR-135a-5p on autophagy of mouse embryonic palatal mesenchymal cells. METHODS:In vitro,palatal mesenchymal cells from C57BL/6J mouse embryos were extracted and cultured.Cell transfections were set up as follows:(1)the cells were divided into control group,miR-135a-5p negative control group and miR-135a-5p mimic group;(2)NC+miR-NC group,KIF3B overexpression group,and miR-135a-5p+KIF3B group:qRT-PCR was performed to verify transfection efficiency of miR-135a-5p and KIF3B.A transmission electron microscope was used to observe the number of autophagosome/autophagolysosome in the cells of each group.The degree of fluorescence expression of autophagy marker LC3B was determined by the immunofluorescence technique.The protein expression of KIF3B,LC3 and P62 was determined by western blot assay.(3)The cells were divided into miR-135a-5p negative control group,and SAG treated group,and SAG+miR-135a-5p group.qRT-PCR was used to detect the mRNA expression levels of Gli3,a key transcription factor downstream of Shh signaling.The protein expressions of autophagy-related proteins LC3 and P62 were detected by western blot assay. RESULTS AND CONCLUSION:(1)After overexpression of miR-135a-5p,the number of autophagosome/autophagolysosome was significantly increased(P<0.01).The fluorescence density of LC3B increased significantly(P<0.01);the protein expression of KIF3B and P62 decreased(P<0.01),and the protein expression of LC3 increased.(2)After overexpression of KIF3B,the number of autophagosome/autophagolysosome was significantly decreased(P<0.01);the fluorescence density of LC3B was decreased(P<0.01);the protein expression of P62 was increased(P<0.01),and the protein expression of LC3 was decreased(P<0.01).Targeted expression of KIF3B was inhibited by miR-135a-5p(P<0.01);the number of autophagosome/autophagolysosome,the fluorescence intensity of LC3B as well as the protein expression of LC3 were reversed(P<0.01)and the protein expression of P62 was decreased(P<0.01).(3)SAG significantly increased the mRNA expression of Gli3(P<0.01),increased the protein expression of P62(P<0.01),and decreased the protein expression of LC3(P<0.01).When miR-135a-5p was added,Gli3 mRNA expression was significantly decreased(P<0.01);P62 protein expression was decreased(P<0.01),and LC3 protein expression was reversed(P<0.01).(4)These results indicate that miR-135a-5p targets the inhibition of KIF3B and promotes autophagy in mouse embryonic mesenchymal cells possibly by negatively regulating the Shh signaling pathway.

Objective To establish an artificial intelligence(AI)diagnostic model for the histopathologic diagnosis of extramammary Paget's disease(EMPD)and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD.Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited,and their pathological data were collected,including EMPD,Bowen's disease(BD),squamous cell carcinoma(SCC),and epidermal hyperplasia and hypertrophy.With EMPD as the main research subject,the histopathological images of BD,SCC,and non-tumor skin diseases were included in the study.The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks,and the performance of these models was evaluated.Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD,BD,SCC and non-tumor skin diseases on the images at x20 magnification were 0.97,0.98,1.00 and 0.96,respectively,with an accuracy of 0.925±0.011,while the AUC values on the images at x40 magnification were 1.00,0.99,1.00 and 0.97,respectively,with an accuracy of 0.943±0.017.The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at x20 magnification were 0.98,0.95,0.99 and 1.00,respectively,with an accuracy of 0.912±0.034,while the AUC values on the images at x40 magnification were 0.99,0.96,1.00 and 1.00,respectively,with an accuracy of 0.971±0.012.Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD,SCC and non-tumor skin diseases at low power magnification.The FLPOs of ResNet101 was 786.6 M,and the parameter was 4.5 M;The FLPOs of DensNet121 was 289.7 M,and the parameter was 0.8M.Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD.DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

Objective:To summarise and analyse the experience in the diagnosis and management of abdominal aortic endograft infection in recent years.Methods:Retrospectively summarised and analysed the general data, clinical presentation, laboratory and imaging findings, causative organisms and treatment choices of 14 patients with abdominal aortic endograft infection treated in Beijing Friendship Hospital, Capital Medical University, from January 2018 to June 2024, and analysed the prognosis of the patients and the risk factors associated with prognosis.Results:Positive bacterial cultures were 10 out of 14 patients. One non-operatively treated patient died of infectious toxic shock. Thirteen surgically treated patients underwent axillary-bifemoral artery bypass, removal of the infected stent, and closure of the aortic stump. Four of the 13 cases had combined aortoenteric fistula, 3 cases underwent one-stage enterocutaneous fistula repair, 1 case only fistula drainage, 3 cases of gastrojejunal anastomosis, all of them underwent gastric or jejunal nutrient tube implantation. Two of the 13 patients had combined the infection foci spread to the renal artery openings. To save the kidney, intraoperative left kidney autologous renal transplantation was performed in 1 case, and autologous saphenous vein reconstruction from celiac trunk artery-left renal artery and superior mesenteric artery-right renal artery was performed in the other case. All 14 patients were retrospectively summarised and followed up in August 2024, with 5 deaths in the early postoperative period (< 3 months), 3 deaths in the mid- to long-term period (≥3 months), and 5 survivors, with a median follow-up time of 2 years (1-5 years) for surviving patients. Among the 13 operated patients, 4 cases were combined with aortoenteric fistula, and 3 cases died in the early postoperative period; 4 cases of abdominal aortic infection foci involving renal artery openings, 2 cases of early postoperative death; 4 cases with pleural effusion, 4 cases died in the early postoperative period; 2 cases of combined creatinine elevation, 2 cases of early postoperative death; 2 cases of postoperative infection of artificial blood vessels.Conclusions:Abdominal aortic endograft infection are aggressive. The risk of early death is increased in patients who are elderly, in poor general condition, with aortoenteric fistula or with pre-existing cardiac, pulmonary, hepatic and renal insufficiency, but surgery based on adequate anti-infective therapy remains an effective means of saving the patient′s life.

Objective:To investigate the application effect of WeChat group combined with case-based learning (CBL) in probation teaching of vascular surgery.Methods:A total of 128 intern doctors of the seven-year medical program in vascular surgery were selected and divided into experimental group (WeChat group combined with CBL teaching) and control group (CBL teaching alone), and a unified assessment method was used to evaluate the mastery degree of professional theories and clinical knowledge and assess the teaching effect of these two teaching modes in vascular surgery. SPSS 22.0 was used to perform the t-test. Results:Compared with the control group, the experimental group had significantly higher scores of theoretical examination [(86.36±7.42) vs. (84.71±6.72)] and clinical examination [(88.44±7.62) vs. (86.22±6.41)], as well as significantly higher degrees of satisfaction with learning interest, classroom climate, self-learning ability, clinical thinking ability, and teamwork spirit.Conclusion:The teaching mode of WeChat group combined with CBL can improve the effect of the probation teaching of vascular surgery and the self-learning and clinical thinking abilities of intern doctors.

This study was aimed at identifying species of ticks and investigating infections with tick-borne pathogens a-mong people in Yadong,Tibet.The total of 23 ticks(Ixodes and Haemaphysalis)collected from livestock in Yadong,Tibet in July 2021,the gene sequences of cytochrome oxidase subunitⅠ(COX Ⅰ),mitochondrial 16S ribosomal DNA(16S rDNA)and mitochondrial 12S ribosomal DNA(12S rDNA)were identi-fied on the basis of molecular biology classification.The gene sequences of spotted fever group rickettsia(SFGR),Borrelia burgdorferi,Francisella tularensis and Coxiella burnetii in ticks were amplified by PCR and sequenced,and phylogenetic ana-lyses were performed.In addition,184 serum samples collected from Yadong in 2021 were screened for antibodies to Lyme dis-ease,Q fever,spotted fever,and tularemia by ELISA,and infections with tick-borne pathogens in Yadong were comprehen-sively analyzed.The ticks(Ixodes)collected in Yadong,Tibet,were grouped into two categories.The COX Ⅰ,16S rDNA,and 12S rDNA gene sequences of the ticks had 99.5％,97.57％,and 99.12％ similarity,respectively,to those of Ixodes nuttallia-nus in GenBank.The similarities between the COX Ⅰ and 16S rDNA gene sequences of another Ixodes tick species and the COXⅠ and 16S rDNA gene sequences of Ixodes ovatus in GenBank were 88.29％ and 95.75％,respectively.The similarity between the COX Ⅰ,16S rDNA,and 12S rDNA gene sequences of Haemaphysalis ticks and those of Haemaphysalis Tibet in GenBank were 96.04％,96.17％,and 97.47％,respectively.The sequence amplification results for Borrelia burgdorferi,Francisella tularensis,and Coxsiella burnetii in 23 ticks were negative,whereas gltA gene amplification of spotted fever group Rickettsia in 23 ticks was positive.The similarity of gltA gene sequences with respect to those of Candidatus Rickettsia tarasevichiae,Rickettsia raoultii,Rickettsia canadensis,and a Rickettsia endosymbiont of Eucalyptus brunneri in GenBank was 96.77％,96.76％,95.35％,and 95.35％,respectively.Among 184 serum samples from Yadong,the positivity rates of Lyme disease,Q fever,spotted fever,and tularemia were 6.52％,12.50％,8.70％,and 10.87％,respectively.These results indicated that the 23 parasitic ticks collected in Yadong,Tibet,in July 2021 were Ixodes nuttallianus,Ixodes ovatus and Haemaphysalis ti-betensis,and 23 ticks were infected with SFGR.Lyme disease,Q fever,spotted fever,and tularemia infection were prevalent in the population of Yadong.Therefore,efforts to control tick-borne diseases must be strengthened.

Gold is one of the mineral medicine and has a long history."Calm the spirit,strengthen the bone marrow,clear five viscera,remove evil gas,and be like the immortal"was written on the"Annotation of Materia Medica",which was the first time to make clear its medicinal value.With the passage of time and the increase of related literature,people have a deeper understanding of the toxicity of gold.In order to avoid the harm caused by toxicity,the use frequency of gold is greatly reduced.There is still a lack of systematic research and sorting in modern researches,and the question of whether gold has medicinal value in Chinese patent medicine has not been deeply explored.Based on the description of ancient materia medica medical books,referring to the modern research results on"gold",this paper focused on the progress of medicinal properties of gold,ancient and modern applications and toxicity understanding,and on this basis,the medicinal value was analyzed,concluded and summarized,and the ancients'correct views on the use of gold was textually researched to provide the basis for further rational drug use in clinical and further development of its medicinal value.

Background: Abnormal expression of leptin and brain⁃derived neurotrophic factor (BDNF) is an important link in the occurrence of ulcerative colitis (UC), but the mechanism of leptin and BDNF in UC is still unclear. Aims: To explore the effect and mechanism of leptin and BDNF in DSS induced colitis in mice. Methods: Thirty⁃six male 8⁃10 weeks healthy leptin⁃deficient ob mice and leptin⁃normal expressing wild type (WT) mice were selected and randomly divided into WT experimental group, ob experimental group, WT control group and ob control group. The mice in experimental groups were given 3% DSS solution for 7 days to induce colitis model, and the mice in control group were given distilled water. After modeling, disease activity index (DAI) score, colon length, behavior and visceral sensitivity were observed. The mRNA expressions of leptin and BDNF in colon and hippocampus were detected by real⁃time fluorescent quantitative PCR, and the protein expression of BDNF in colon was detected by Western blotting. Results: Compared with corresponding control groups, DAI score, visceral sensitivity in WT experimental group and ob experimental group were significantly increased (P< 0.05), mRNA and protein expressions of BDNF in colon were significantly increased (P<0.05). Compared with WT control group, anxiety and depression⁃like behavior were found in WT experimental group, mRNA expressions of leptin, BDNF in hippocampus were significantly decreased (P<0.05). Correlation analysis showed that anxiety was positively correlated with length of colon in WT experimental group (P<0.05), and negatively correlated with DAI score (P<0.05); depression, expression of BDNF mRNA in colon were negatively correlated with length of colon (P<0.05), and positively correlated with DAI score (P<0.05); leptin in hippocampus was positively correlated with anxiety (P<0.05), while was negatively correlated with depression (P<0.05); expression of BDNF mRNA in colon was negatively correlated visceral sensitivity (P<0.05). Conclusions: Colonic BDNF secretion is associated with leptin expression, and both may be involved in the DSS⁃induced colitis in mice by mediating anxiety, depression and visceral sensitivity.

OBJECTIVE To study the tocolysis effects of Angelica sinensis polysaccharides on threatened abortion model rats and their impacts on Th1/Th2 balance by regulating the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway. METHODS Pregnant rats were randomly grouped into the control group， model group， A. sinensis polysaccharide group （200 mg/kg）， PI3K/AKT signaling pathway inhibitor LY294002 group （5 mg/kg）， and A. sinensis polysaccharide+LY294002 group （200 mg/kg A. sinensis polysaccharide+5 mg/kg LY294002）， with 10 rats in each group. Except for the control group， rats in all other groups were given mifepristone （8.3 mg/kg） and misoprostol （100 μg/kg） intragastrically to establish a threatened abortion model， and intragastric or intraperitoneal injection of corresponding drugs. The serum levels of estrogen， progesterone， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， and interleukin-4 （IL-4） in each group of rats were detected， and the uterine ovarian index and embryonic mortality rate of rats in each group were measured； the morphology of uterine tissue in rats was observed in each group； Th1/Th2 balance in peripheral blood of rats as well as the expression of PI3K/AKT signaling pathway-related proteins in the uterine tissues of rats in each group were detected. RESULTS Compared with the control group， the uterine tissue of rats in the model group showed pathological damage； the serum levels of estrogen， progesterone and IL-4， uterine ovarian index， peripheral blood Th2 cell ratio， and the ratios of phosphorylated PI3K （p-PI3K）/PI3K and phosphorylated AKT （p-AKT）/AKT in uterine tissue were all decreased （P＜0.05）； the embryo mortality rate， Th1 cell ratio， Th1/Th2 ratio， and serum levels of IFN-γ and TNF-α were increased （P＜0.05）. Compared with the model group， the pathological damage of uterine tissue in the A. sinensis polysaccharide group was reduced， and the above indexes were all improved significantly （P＜0.05）； LY294002 could weaken the effect of A. sinensis polysaccharide on model rats （P＜0.05）. CONCLUSIONS A. sinensis polysaccharides can improve Th1/Th2 imbalance in threatened abortion model rats by activating the PI3K/AKT signaling pathway， thereby inhibiting immune inflammation， and promoting embryo survival.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.