Gastric cancer is the leading cause of cancer-related mortality. Targeted drug therapy is one of the most important therapeutic means for gastric cancer. Human epidermal growth factor receptor 2 (HER2) is an important therapeutic target for gastric cancer. Trastuzumab is a monoclonal antibody that targets HER2. The ToGA trial has established trastuzumab in combination with chemotherapy as the standard treatment for patients with HER2-positive advanced gastric cancer. This article reviews the progress in ToGA experiment, trastuzumab combined with other chemotherapy drugs, trastuzumab combined with other HER2-targeted drugs, trastuzumab and other drug conjugate, and trastuzumab combined with other targeted drugs in the treatment of HER2-positive advanced gastric cancer. Trastuzumab combined with S-1 and other chemotherapeutic drugs has shown good efficacy and safety; the combination of pertuzumab and trastuzumab did not meet the primary endpoint; trastuzumab emtansine (T-DM1) showed no benefit in improving overall survival in patients with HER2-positive advanced gastric cancer. KN026, trastuzumab deruxtecan (T-DXd), Trastuzumab and Pembrolizumab combined chemotherapy, as well as bevacizumab and trastuzumab combined with capecitabine and oxaliplatin are the most progress research advances in the treatment of HER2-positive advanced gastric cancer.

[Objective] To understand the resistance mechanisms, virulence characteristics, and pathogenicity of hypervirulent Klebsiella pneumoniae (hvKp), which causes pyogenic liver abscess (PLA), and to provide related data for clinical treatment of infection caused by this type of bacteria. [Methods] We collected three strains of Klebsiella pneumoniae isolated from the liver abscess fluid of patients with liver abscesses in various departments of The First Affiliated Hospital of Xi’an Jiaotong University. The hypervirulent phenotypes were determined by the wire test, and drug sensitivity was assessed using the VITEK 2 compact automatic microbiological analyzer. Molecular characteristics such as podocarp serotypes, multi-locus sequence typing (MLST), virulence genes, and drug resistance genes were identified through whole-genome sequencing. Additionally, a mouse infection model was established to evaluate pathogenicity. [Results] The isolates were sticky, with mucous thread pulling length >5 mm, all of which exhibited high viscosity phenotypes. Except 146007, which is a multidrug-resistant bacterium, the other two strains had higher antibiotic sensitivity. Whole genome sequencing revealed that the isolates were of high-virulence type, carrying the toxin plasmid rmpADC/rmpA2, iron uptake system, bacterial hairs, secretion system, and other virulence factors. All the three isolates tested positive for rmpA/rmpA2 combined with iucA/iutA, indicating they could be classified as hvKp. Multiple resistance genes were detected, such as β-lactamase like blaTEM, blaSHV, and blaCTX-M. The isolates were highly pathogenic to mice, as evidenced by the diseased organs of the deceased mice observed on autopsy. [Conclusion] The three strains of hvKp isolated in this study carried multiple drug-resistant genes and were highly pathogenic, which suggests that in laboratories and clinical practices it is imperative to promptly identify and adopt necessary disposal strategies to prevent further spread of hvKp.

[Objective] To illuminate that the high expressions of liver X receptor (LXR), cyclooxygenase-2 (COX-2), and cholesteryl ester transfer protein (CETP) are protective factors in the pathogenesis of obesity and obstructive sleep apnea-hypopnea syndrome (OSAHS), in order to provide basic information for the prevention and treatment of obesity in children with OSAHS. [Methods] A total of 24 young rats aged 3-4 weeks were randomly divided into normal control group, obesity group, OSAHS group, and obesity and OSAHS group. We used hematoxylin-eosin (HE) staining to observe the histopathological changes in the liver of the young rats, Western blotting and immunohistochemistry to test the expression levels and distribution of LXRα, COX-2, and CETP in liver tissues of the rats. [Results] The body weight, total cholesterol (TC), and triglyceride (TG) content of the rats in obesity group and obesity+ OSAHS group were significantly increased compared with that in the control group (P<0.05), and the oxygen saturation of the rats in OSAHS group and obesity+ OSAHS group was significantly decreased compared with that in the control group (P<0.05). The liver tissue had significant damage in obesity group, OSAHS group and obesity+ OSAHS group compared with that in the normal control group, and obesity+ OSAHS group had the most severe liver tissue damage. The expression levels of LXRα, COX-2, and CETP were significantly higher in the liver tissues of young rats in OSAHS group and obesity group compared with those in the normal control group (P<0.05). The expression levels of LXRα, COX-2, and CETP were significantly higher in the liver tissues of young rats in obesity+ OSAHS group compared with those in the other groups (P<0.05). [Conclusion] LXR and its target genes COX-2 and CETP are highly expressed in the liver tissues of obese OSAHS rats and are possible protective factors in the pathogenesis of obesity and OSAHS.

[Objective] To investigate the inhibitory effect of quercetin on cisplatin-resistant human colorectal cancer (CRC) cells SW480 and SW620 and its possible mechanism. [Methods] Cisplatin-resistant subtypes of SW480 and SW620 cells were first cultured and the effects of quercetin on cell proliferation and chemosensitivity were determined by MTT assay. Flow cytometry was used to detect apoptosis and protein blotting was used to detect the expressions of relevant proteins. [Results] MTT assay showed that quercetin at the concentrations of 80 μmol/L and 160 μmol/L significantly inhibited the proliferation of SW480 and SW620 cells. Flow cytometry results showed that the apoptosis rate was significantly higher in the cisplatin combined with quercetin group than in the other three groups. Protein blotting showed that cleaved-caspase-3 and caspase-9 expressions were significantly increased in the cisplatin combined with quercetin group. The chemotherapeutic drug sensitivity assay showed that the elevated IC50 of drug-resistant cells was decreased significantly after quercetin administration (P<0.05). [Conclusion] The present study clarifies that quercetin can increase the sensitivity of human CRC cells to cisplatin. This effect may be related to its mechanism of action in affecting cell proliferation, apoptosis and autophagy.

[Objective] To predict potential target genes for the treatment of glioblastoma (GBM) with stigmasterol and construct a relevant prognostic model, in order to reveal its antiglioma mechanism and the role of these target genes in the prognosis of GBM patients. [Methods] Differential expression genes in GBM and stigmasterol target genes were obtained via online databases. Venn diagram was used to select potential target genes for stigmasterol treatment of GBM, and enrichment analysis was performed using R language. Univariate COX regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were made to select stigmasterol target genes related to the prognosis of GBM patients and construct a relevant prognostic model. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting analyses were used to detect the effect of stigmasterol on the expressions of related target genes. [Results] In this study, a total of 31 potential target genes for the treatment of GBM with stigmasterol were identified. Enrichment analysis showed that these target genes were associated with the activation of the G protein coupled receptor (GPCR) signaling pathway and the regulation of lipid metabolism. Regression analysis identified two stigmasterol target genes, namely, fatty acid binding protein 5 (FABP5) and alpha 1B adrenergic receptor (ADRA1B), which are associated with the prognosis of GBM. A prognostic model constructed based on these two genes could accurately predict the prognosis of GBM patients. Finally, stigmasterol inhibited the expressions of these two genes in GBM cells (FABP5: t=9.909, P=0.001; ADRA1B: t=3.319, P=0.029). [Conclusion] Stigmasterol’s anti-tumor effect may be linked to its regulation of GPCR signaling pathways and lipid metabolism. By inhibiting the expressions of FABP5 and ADRA1B, stigmasterol could potentially enhance the prognosis for GBM patients. Additionally, a prognostic model based on the expression levels of FABP5 and ADRA1B can be valuable for predicting patient outcomes and monitoring therapeutic efficacy in GBM.

[Objective] To investigate the effects of fluoride on kallikrein-4 (KLK4) and cell apoptosis as well as the possible mechanisms in ALC cells. [Methods] ALC cells were treated with different concentrations of fluoride for 24 and 48 hours. The effects on cell viability, cell cycle and cell apoptosis were detected using CCK-8, flow cytometry and hoechst 33342, respectively. KLK4 expression was detected by qRT-PCR and Western blotting, and the protein expressions of glucose-regulated protein 78 (GRP78), p-eukaryotic initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) were detected by Western blotting. [Results] The results showed that the expression of KLK4 was significantly reduced after treatment with 1.0 and 2.0 mmol/L NaF for 24 and 48 hours (P<0.05). The difference was statistically significant in cell activity between 2.0 mmol/L NaF treatment group and the control group (P<0.05). The G0/G1 phase cells significantly reduced and the S phase cells significantly increased after treatment with 0.1 and 1.0 mmol/L NaF for 24 hours (P<0.05), while the G0/G1 phase cells significantly increased and the S phase cells significantly reduced in the 2.0 mmol/L NaF treatment cells (P<0.05). The G0/G1 phase cells significantly increased and G2/M phase cells significantly reduced after treatment with 2.0 mmol/L NaF for 48 hours (P<0.05). With the increase of NaF treatment concentration, the number of bright blue cells gradually increased, and the percentage of apoptosis also increased successively. Except for the cells treated with 0.1 mmol/L NaF for 24 hours, the apoptosis rate of the other fluoride treatment groups was statistically significant compared with the control group (P<0.05). The expressions of GRP78 and p-eIF2α were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 1.0 and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 48 hours (P<0.05). [Conclusion] Sodium fluoride may result in inhibition of KLK4 expression and abnormal cell growth, possibly by inducing GRP78 expression and activating eIF2α/ATF4/CHOP signaling pathway in ALC ameloblasts.

[Objective] The aim of this study was to investigate the protective role of programmed cell death ligand-1 (PD-L1) in a mouse model of spinal cord injury (SCI) by regulating T cell immunity and the PI3K/Akt/mTOR signaling pathway. [Methods] C57BL/6 mice used to establish SCI models were divided into the sham operation group (Sham), SCI group, SCI+ PD-L1 antibody group (SCI+ Ab), and SCI+ PD-L1 protein group (SCI+ PRO). c57BL/6 mice and PD-L1 knockout mice were used for SCI mapping, and they were divided into the sham operation group (Sham WT), PD-L1 knockout sham operation group (Sham PD-L1 KO), SCI model group (SCI WT), and PD-L1 knockout SCI model group (SCI PD-L1 KO). Western blotting and qRT-PCR were applied to detect the expression of PD-L1 in spinal cord tissues at different time points after SCI; mouse motor function was assessed by the Basso Mouse Motor Scale (BMS); changes in the levels of inflammatory factors and T-cell subpopulations after SCI were analyzed using qRT-PCR and flow cytometry; and Western blotting was used to detect changes in the PI3K/Akt/mTOR signaling pathway activation. [Results] PD-L1 expression was upregulated in spinal cord tissues of mice subjected to SCI palliation, peaking on day 7. Compared with the SCI PD-L1 KO group, mice in the SCI WT group had significantly higher BMS scores at 7, 14, and 28 days after SCI (P<0.05), and the levels of inflammatory factors IL-1α, IL-2, IFN-γ and TNF-α were significantly lower on day 7 after palpation (P<0.05). Compared with the SCI+ PBS group, mice in the SCI+ PRO group had significantly higher Foxp3 levels and significantly lower Th1 and Th17 levels. Foxp3 levels were significantly higher, but Th1 and Th17 cell levels were significantly lower, and Th2 and Treg cell levels were significantly higher (P<0.05). The phosphorylation of the PI3K/Akt/mTOR signaling pathway was significantly higher in the SCI WT group mice than the SCI PD-L1 KO group ones (P<0.05). In contrast, the phosphorylation of PI3K/Akt/mTOR signaling pathway was significantly lower in the SCI+ PRO group than in the SCI+ PBS group and the SCI+ Ab group (P<0.05). [Conclusion] PD-L1 plays a neuroprotective role by regulating the balance of Th1, Th17, Th2 and Treg cells and inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing the inflammatory response after SCI. PD-L1 is expected to be a new target for the treatment of SCI.

[Objective] To investigate the role of miR-199a-3p on mouse skin scar fibroblasts and the potential target of miR-199a-3p. [Methods] A mouse skin keloid model was established. The mRNA levels of miR-199a-3p, Smad1 and keloid related genes in keloid tissues and normal skin tissues were detected by Real-time quantitative PCR. C57BL/6 mouse skin fibroblasts were isolated and cultured for the cellular experimental study. miR-199a-3p mimic and Smad1 siRNA matter were transiently transfected into mouse skin fibroblasts by liposome reagent. the interaction between miR-199a-3p and the 3′-UTR of Smad1 was confirmed by the dual luciferase reporter assay. The expressions of Smad1 and keloid-related genes at mRNA and protein levels after transfection of miR-199a-3p mimic were determined. The expressions of Smad1 and keloid-related genes at protein level after transfection of miR-199a-3p mimic and Smad1 siRNA were determined by Western blot assay. [Results] Compared with normal skin tissues, the expressions of Smad1 (t=-4.403, P=0.010) and keloid related genes, Col1a1(t=-3.334, P=0.016), Col3a1(t=-5.927, P=0.001) and ACTA2(t=-3.673, P=0.010), were significantly increased in keloid tissues, while miR-199a-3p (t=7.059, P<0.001) expression was significantly decreased. Over-expression of miR-199a-3p could significantly decrease the expressions of keloid-related genes, Col1a1 (t=5.514, P=0.005), Col3a1 (t=5.132, P=0.014) and ACTA2 (t=4.136, P=0.026), in mouse skin fibroblasts. Moreover, the dual luciferase reporter assay revealed that miR-199a-3p could interact with the 3′-UTR of Smad1. miR-199a-3p was observed to inhibit Smad1 at mRNA expression level (t=3.556, P=0.024), and at the post-transcriptional level (t=3.781, P=0.019). Meanwhile, miR-199a-3p mimic, in parallel to Smad1 siRNA, decreased the expressions of keloid-related genes, Col1a1 (F=18.804; P=0.003, 0.022), Col3a1 (F=33.212; P=0.001, 0.001) and α-SMA (F=10.181; P=0.020, 0.028), and decreased the proliferation of skin fibroblasts (F=18.622; P=<0.001, <0.001). [Conclusion] miR-199a-3p inhibits the formation of keloid by targeting Smad1.

[Objective] To explore the safety and effectiveness of provisional stenting (PS) applied in patients with unprotected simple left main bifurcation lesions, and to observe the impact of this procedure on cardiac function, myocardial injury, and myocardial perfusion. [Methods] A retrospective analysis was made on 82 patients with unprotected simple left main bifurcation lesions who underwent elective stenting and completed a 3-month follow-up in the Department of Cardiology, Hebei Medical University First Hospital. All the patients underwent preoperative examinations, including rest dynamic single-photon emission computed tomography (D-SPECT) and regadenoson stress D-SPECT before and 3 months after surgery. The safety evaluation indicators for the surgery included immediate success rate of stent implantation, acute stent thrombosis, coronary no-reflow, branch involvement, branch acute occlusion, acute left heart failure, heart block, cardiac tamponade, major bleeding, and mortality. The effectiveness evaluation indicators included the minimum lumen area (MLA) of the left main trunk of coronary artery measured by intravenous ultrasound (IVUS) before and after surgery, as well as cardiac function indicators [brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD)] and myocardial injury indicators [creatine kinase isoenzyme-MB (CK-MB), cardiac troponin Ⅰ (cTn Ⅰ)] at day 1, day 7, 1 month, and 3 months before and after surgery. The myocardial perfusion evaluation indicators included the total myocardial perfusion score and total ischemic segment number under the 17-segment distribution of myocardial perfusion using rest D-SPECT and regadenoson stress D-SPECT before and 3 months after surgery. [Results] Safety indicators: immediate success rate of stent implantation (100%), 19 cases (23.1%) of circumflex branch involvement that underwent balloon anastomosis dilation, 1 case of acute branch occlusion, followed by double stent surgery using provisional stenting-T stenting (PS-T) technique. There were no cases of acute stent thrombosis, coronary reflow, acute left heart failure, cardiac block, cardiac tamponade, major bleeding, or death. Effectiveness indicators: the MLA of the left main trunk measured by postoperative IVUS showed significant improvement compared to the preoperative. BNP, CK-MB, and cTnⅠ showed significant improvement from day 7 after surgery compared to before. Myocardial perfusion indicators: the total score of myocardial perfusion and the total number of ischemic segments in the 17-segment distribution of the myocardium after 3 months of surgery were significantly better than before. [Conclusion] PS can improve heart function, myocardial injury, and myocardial perfusion in patients with unprotected simple left main bifurcation lesions.

[Objective] To investigate the value of total cholesterol to high-density lipoprotein cholesterol ratio (THR), monocyte to high-density lipoprotein cholesterol ratio (MHR), and neutrophil to high-density lipoprotein cholesterol ratio (NHR) in predicting patients’ coronary artery stenosis severity and percutaneous coronary intervention (PCI). [Methods] A total of 6 281 patients who underwent coronary angiography at our hospital between June 2021 and June 2023 were retrospectively included in this study. These patients were divided into two groups: PCI group and non-PCI group. The clinical data, laboratory findings, and interventional treatment data of all patients were collected and analyzed. Pearson correlation analysis was employed to evaluate the correlation of THR, MHR and NHR with the degree of coronary artery stenosis. Binary Logistic stepwise regression and receiver operating characteristic (ROC) curve were utilized to assess the influencing factors and predictive value of THR, MHR and NHR single and combined indexes for coronary artery disease patients undergoing PCI. [Results] The PCI group was observed to be older, with a higher proportion of males, individuals with diabetes mellitus, and those who had undergone THR, MHR, NHR, and a Gensini score than the non-PCI group. Conversely, the proportion of previous stent implantation was less than that of the non-PCI group (P<0.05). The results of Pearson correlation analysis showed a significant and positive correlation of the Gensini score with THR (r=0.351, P<0.001), MHR (r=0.192, P<0.001), and NHR (r=0.236, P<0.001) levels, indicating that these variables had a significantly positive correlation with the degree of coronary artery stenosis. The results of multifactorial Logistic regression demonstrated that age >50 years, male sex, diabetes mellitus, THR, MHR, and NHR were independent risk factors for PCI in patients with coronary artery disease. Conversely, a history of previous stent implantation was identified as a protective factor for PCI in patients with coronary artery disease. Furthermore, the results of ROC curves indicated that the combined area under the curve (AUC) was the largest for THR, MHR, and NHR (AUC=0.809, 95%CI: 0.798-0.820). [Conclusion] THR, MHR and NHR correlate with the degree of coronary stenosis and have strong clinical applications in the assessment of coronary artery disease for PCI.