A Novel Air-Cooled Nd:YAG Laser for the Treatment of the Venous Lakes of the Lips.

Objective: To evaluate the therapeutic effect of a novel air-cooled Nd:YAG laser in the venous lakes of the lips (VLL). Background: The thermal injury is one of the most important issues during laser therapy for venous lakes. Methods: Six pieces of fresh pork livers were used to provide 30 regions with a diameter of 6 mm for experiment in vitro, among which 15 regions were treated by Nd:YAG laser with air cooling until the tissue turned gray-white, whereas the rest were treated without air cooling as control. The operation time of laser irradiation, the degree of temperature increase, and the depth of coagulation tissue were compared between two groups. Then, 60 VLL patients were selected for Nd:YAG laser treatment with or without air cooling. The operation time of laser irradiation, the degree of temperature increase, the postoperative pain visual analog scale (VAS) score, and the percentage of lesions removed within 1 month were compared. Results: In tissue studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and there was no significant statistical difference in the depth of coagulation tissue (p = 0.624). In clinical studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and a lower VAS score on the 1st and 2nd day, compared with the control group (p < 0.01). Conclusions: Air cooling during Nd:YAG laser for the treatment of VLL can prolong the surgical time, but lowered tissue temperature and reduced patient pain within 2 days under the premise of ensuring the treatment effect.

A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer.

BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.

Current status and prospect of treatments for recurrent hepatocellular carcinoma.

Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.

Simultaneous Determination of Voriconazole and Its Voriconazole N-Oxide Metabolite in Human Urine by Liquid Chromatography/Tandem Mass Spectrometry.

A convenient and sensitive liquid chromatography-tandem mass spectrometry method was established to simultaneously quantify voriconazole (VRZ) and its metabolite, voriconazole N-oxide (VNO), in human urine. Voriconazole-d3 and voriconazole-d3 N-oxide were used as isotopic internal standards. Samples were processed by protein precipitation and separated using a ZORBAX SB-Aq column (1.8 µm, 2.1 × 50 mm). Mass spectrometry was performed using an API 4000 mass spectrometry by positive electrospray ionization. The flow rate was 0.6 mL/min. Gradient elution was performed with methanol and 0.1% formic acid as the organic and water phase, respectively. The VRZ and VNO calibration curves ranged from 20.0 to 7200 ng/mL in human urine. The specificity, matrix effect, extraction recovery, intra/inter-run precision, accuracy and stability were validated for both VRZ and VNO in human urine. The developed method was used to study urinary excretion after intravenous injection of 4 mg/kg VRZ in healthy Chinese subjects.

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance.

OBJECTIVE: The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. DESIGN: The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. RESULTS: Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. CONCLUSION: There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH.

Meta-analysis of the MDM2 T309G polymorphism and gastric cancer risk.

BACKGROUND: Mdm2 binds to the amino-terminus of p53 to induce its degradation and a single nucleotide polymorphism in the MDM2 promoter region (T309G) has been reported to increase the risk of several carcinomas, such as gastric cancer. However, the results of published studies to analyze the association between MDM2 T309G and gastric cancer havve often conflicted. METHODS: To better illustrate the filiation between MDM2 T309G and gastric cancer, we performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the relationship. The pooled ORs were performed for 4 models, additive, recessive, co-dominant model, and dominant. RESULTS: Nine published case-control studies including 3,225 gastric cancer cases and 4,118 controls were identified. The MDM2 T309G polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR=1.57; 95%CI=1.57-2.12; p=0.003) and GG versus GT/TT, OR=1.52; 95%CI=1.217-1.90; p<0.001). Furthermore, Egger

[Study on effect of sophoridine against bone cancer pain and its mechanism].

OBJECTIVE: To study the effect of sophoridine against bone cancer pain in bone cancer pain model rats induced by W256 tumor cells and its mechanism. METHOD: The rat model of bone cancer pain was reproduced by injecting W256 tumor cells into the rat marrow cavity. Ten days after the model establishment, 36 rats were selected and randomly divided into the model control group and the sophoridine treated group. At the same time, other 10 rats with sham-operation were selected to be the normal control group. Since the 15th day after the operation, rats in the treated group had been given sophoridine (25 mg x kg(-1)) for 10 days. The mechanical withdrawal threshold and the thermal withdrawal latency of each group were measured before and after the treatment. After the last treatment, the radiological and histopathological observation shall be conducted for sick legs of all rats. The expressions of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in tumor tissues were detected by mmunohistochemistry. RESULT: Sophoridine could significantly increase the mechanical withdrawal threshold and the thermal withdrawal latency (P < 0.05, P < 0.01), significantly relief the bone injury caused by W256 tumor cells (P < 0.05), and notably down-regulate the COX-2 and VEGF expressions in tumor tissues (P < 0.05). CONCLUSIONS: Sophoridine has the effect in relieving pain and inhibiting tumor progression in bone cancer pain rats induced by W256 tumor cells. Its mechanism may be related to the down-regulated expressions of COX-2 and VEGF.

Cytochrome P450 ω-hydroxylase promotes angiogenesis and metastasis by upregulation of VEGF and MMP-9 in non-small cell lung cancer.

PURPOSE: Cytochrome P450 (CYP) ω-hydroxylase, mainly consisting of CYP4A and CYP4F, converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) that induces angiogenic responses in vivo and in vitro. The present study examined the role of CYP ω-hydroxylase in angiogenesis and metastasis of human non-small cell lung cancer (NSCLC). METHODS: The effect of WIT003, a stable 20-HETE analog, on invasion was evaluated using a modified Boyden chamber in three NSCLC cell lines. A549 cells were transfected with CYP4A11 expression vector or exposed to CYP ω-hydroxylase inhibitor (HET0016) or 20-HETE antagonist (WIT002), and then ω-hydroxylation activity toward arachidonic acid and the levels of matrix metalloproteinases (MMPs) and VEGF were detected. The in vivo effects of CYP ω-hydroxylase were tested in established tumor xenografts and an experimental metastasis model in athymic mice. RESULTS: Addition of WIT003 or overexpression of CYP4A11 with an associated increase in 20-HETE production significantly induced invasion and expression of VEGF and MMP-9. Treatment of A549 cells with HET0016 or WIT002 inhibited invasion with reduction in VEGF and MMP-9. The PI3 K or ERK inhibitors also attenuated expression of VEGF and MMP-9. Compared with control, CYP4A11 transfection significantly increased tumor weight, microvessel density (MVD), and lung metastasis by 2.5-fold, 2-fold, and 3-fold, respectively. In contrast, WIT002 or HET0016 decreased tumor volume, MVD, and spontaneous pulmonary metastasis occurrences. CONCLUSION: CYP ω-hydroxylase promotes tumor angiogenesis and metastasis by upregulation of VEGF and MMP-9 via PI3 K and ERK1/2 signaling in human NSCLC cells.

[Relationship between genetic polymorphisms of metabolizing enzymes and prostate cancer].

OBJECTIVES: To study the possible relationship between CYP1A1, NAT2 genetic polymorphisms and the susceptibility of prostate cancer. METHODS: Forty-eight patients with prostate cancer and 112 healthy cases were selected as the control randomly. NAT2 and CYP1A1 gene polymorphisms were analysed with the methods of PCR-RFLP, ASA and real-time fluorescence Light-Cycler. The difference of frequency between the patients and the controls was compared. RESULTS: Among prostate cancer patients and their matched controls, the frequencies of alleles and genotypes were significantly different with Ile-Val gene Polymorphisms (P < 0.05), in which the frequency of the allele G and GG genotypes were significantly higher than those in their matched controls with an odds ratio of 1.59 and 3.06(P < 0.05), respectively; No significant differences of the frequencies of the MspI alleles and genotypes were found between the patients with prostate cancer and the matched controls(P > 0.05). No significant differences of NAT2 slow acetylator genotype frequency were found between the controls and prostate cancer patients (P > 0.05). CONCLUSIONS: The CYP1A1 Ile-Val gene polymorphisms might be associated with the occurrence of prostate cancer, while MspI gene polymorphisms and NAT2 slow acetylator genotype might not be associated with the occurrence of prostate cancer.