Lung cancer is the leading cause of death worldwide. With the prevalence of CT screening and early diagnosis and treatment of lung cancer in China, more and more patients with early-stage lung cancer characterized with ground-glass opacity are discovered and urgently require treatment, which poses a significant challenge to surgeons. As an emerging technology, three dimensional reconstruction technology plays a crucial auxiliary role in clinical work. This review aims to briefly introduce this technology, focusing on its latest advances in surgical applications in early lung cancer screening, malignant risk assessment, and perioperative period application and medical education.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Objective To study the synergistic effects of gentiopicroside combined with pabolizumab on photodynamic therapy in mice with breast cancer.Methods MCF-7 cells were injected subcutaneously to establish a tumor bearing mouse model of breast cancer and were randomly divided into model group,control group,positive control group,experimental group and combination group,with 10 mice in each group.The control group was intraperitoneally injected with 50 mg·kg-1 of 5-aminolevulinic acid and irradiated with 200 J·cm-2 laser for 20 min,once a week.The positive control group was intraperitoneally injected with 100μg·kg-1 pabolizumab,twice a week,and photodynamic therapy once a week,the experimental group was intragastric given 100 mg·kg-1 gentiopicroside,once a day,and photodynamic therapy once a week,the combined group was intraperitoneally injected with pabolizumab(100 μg·kg-1),twice a week,and gavage of gentiopicroside(100 mg·kg-1)once a day and photodynamic therapy once a week.Five groups of mice were given the drug for 3 weeks.The tumor inhibition rate of each group was compared,and the levels of interleukin(IL)-12,interferon(INF)-γand tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.The levels of B-cell lymphoma-2 associated gene(Bax),B-lymphoblastoma-2 gene(Bcl-2)and vascular endothelial growth factor(VEGF)protein in tumor tissues were determined by Western blot.Results The tumor inhibition rates of control,positive control,experimental and combined groups were(22.38±2.26)％,(42.27±3.21)％,(38.16±2.17)％and(60.24±2.84)％,respectively.The serum IL-12 levels of model,control,positive control,experimental and combined groups were(127.13±1.25),(132.29±2.31),(155.27±1.48),(163.31±2.67)and(185.24±1.71)pg·mL-1;INF-γ levels were(724.16±3.63),(891.12±4.45),(1 043.19±3.85),(1 082.34±4.51)and(1 492.13±6.57)pg·mL-1;TNF-α levels were(83.81±4.52),(65.26±3.77),(41.07±3.85),(43.59±3.94)and(27.12±3.93)pg·mL-1;the relative protein expression levels of Bax were 0.30±0.08,0.47±0.05,0.67±0.11,0.89±0.06 and 1.03±0.10;the relative protein expression levels of Bcl-2 were 0.99±0.04,0.86±0.06,0.71±0.05,0.46±0.06 and 0.31±0.08;the relative protein expression levels of VEGF were 1.06±0.04,0.92±0.03,0.76±0.04,0.49±0.04 and 0.29±0.08.The differences of above indexes between the combined group and the control,positive control group and experimental groups were statistically significant(all P＜0.05).Conclusion Gentiopicroside combined with pembrolizumab can significantly enhance the tumor inhibition effect of photodynamic therapy on breast cancer mice,promote the apoptosis of breast cancer cells,and then inhibit the tumor progression of breast cancer mice.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

Temporomandibular disorders (TMD) are a heterogeneous group of diseases that affect the temporomandibular joint, chewing muscle system, dental occlusion, and even various structures throughout the body, with significant characteristics of biological-psychological-social pattern. TMD related chronic pain, as the most important clinical symptom, can result in negative emotions seriously affecting patients′ quality of life and physical and mental health. Although a variety of therapies have been previously reported to treat TMD related chronic pain, there is a lack of widely recognized therapies. Professor Jason W Busse (from Michael G DeGroote National Pain Centre, McMaster University, Hamilton ON, Canada) took the lead and collaborated with multiple internationally renowned schools/hospitals of stomatology to develop an international consensus on the management of chronic pain associated with TMD, a clinical practice guideline, which took two years and was published in December 15th, 2023 in a global top journal of clinical research The British Medical Journal. This clinical practice guideline explored the comparative effectiveness of available therapies for chronic pain associated with TMD, conditionally recommended the specific intervention for different treatment or pain relief, proposed a comprehensive, agreed, and standardized clinical practice guideline. This present article describes the methodology and key elements of the clinical practice guideline to help clinicians fully understand and appropriately apply this guidance, which could provide the references for clinical practice of TMD associated chronic pain in China.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.