The biofilm is a major pathogenic factor for many types of chronic infections,and Escherichia coli bio-film plays an important role in community-acquired infection and hospital-acquired infection and is one of common causes of urinary tract infection(UTI).The quorum sensing(QS)system of E.coli biofilm can mediate intercel-lular information exchange and thus regulate the whole community to adapt to the environmental changes,and the extracellular matrix-derived complex resistance mechanisms lead to a certain degree of bacterial resistance to anti-microbial drugs and resistance to immune system,which then makes it difficult for the conventional antimicrobial drugs to effectively eradicate the biofilm-associated infections.The article focuses on the formation of E.coli bio-film,drug resistance mechanisms and treatment aspects and summarizes the progress of research on the novel substitutive therapies against the E.coli biofilms that were developed in recent years,such as phytochemicals,nanomaterials,probiotics and phage therapy,so as to provide theoretical bases for the clinical treatment and the development of novel drug therapies against the E.coli biofilm.

Objective To develop an ultra-high performance liquid chromatography-mass spectrometry method(UPLC-MS/MS)for the determination of nirmatrelvir concentration in mouse plasma.Methods The ACQUITY UPLC system was used in tandem with an API 4000 triple quadrupole mass spectrometer.The analytical column was Waters BEH C18(2.1 mm×5.0 mm,1.7 μm)column,and the mobile phases consisted of water(containing 0.1％formic acid)and methanol(containing 0.1％formic acid)under gradient elution at the flow rate of 0.4 mL·min-1.The column temperature was set at 40 ℃,and the injection volume was 5 μL.Electrospray ionization was used as ion source,and positive multiple reaction monitoring mode was adopted to quantitatively analyze the ionization pairs m/z 500.3→110.3(nirmatrelvir)and m/z 237.3→193.3(carbamazepine).Carbamazepine was employed as an internal standard.Results The linear range of nirmatrelvir was from 10 ng·mL-1 to 2 560 ng·mL-1.For the quality control nirmatrelvir samples,the accuracies of intra-and inter-batch were less than±15％,and the precisions of intra-and inter-batch were lower than 15％.Nirmatrelvir in plasma was stable at room temperature for 24 h and remained stable after three freeze-thaw cycles.The extracted nirmatrelvir solution could be stored at 4℃ for 3 d without any visible change.Conclusion The method was characterized by good specificity,high sensitivity,and appropriate linear range.The methodological validation was in accordance with the 2020 edition of the Chinese Pharmacopoeia and could be applied to the quantitative detection of nirmatrelvir in plasma.

Objective:To apply patent metrics to analyze the distribution, development trends, and characteristics of patents related to orthokeratology lenses for assisted wearing, providing a reference for the research and development of such patents.Methods:Patents related to orthokeratology lenses for assisted wearing were retrieved by computer from the China National Intellectual Property Administration database, incopat, Derwent Innovations Index, Free Patents Online, Organisation Africaine de la Propriété Intellectuelle, and IP Australia. The search timeframe was from the establishing of these databases until March 8, 2024. Patent metrics methods, word frequency analysis, and high-frequency word co-occurrence analysis were used for data analysis.Results:A total of 60 relevant patents were selected. The development of orthokeratology lens-assisted wearing patents began relatively late but has shown a strong growth trend, reaching a peak around 2015. Chinese patents accounted for the largest share (91.7%, 55/60) , with Zhejiang Province, Beijing City, Jiangsu Province, Guangdong Province, and Shanghai City having the highest number of patents. The majority of the applicants were enterprises. The research focus in this field is on mechanical assistance patents for lens wearing, with cutting-edge technologies focusing on monitoring the displacement of lenses relative to the pupil and providing timely feedback and guidance.Conclusions:This study, using patent metrics, word frequency analysis, and high-frequency word co-occurrence analysis, provides a reference for patent applications and product development in orthokeratology lens-assisted wearing in nursing.

The biofilm is a major pathogenic factor for many types of chronic infections,and Escherichia coli bio-film plays an important role in community-acquired infection and hospital-acquired infection and is one of common causes of urinary tract infection(UTI).The quorum sensing(QS)system of E.coli biofilm can mediate intercel-lular information exchange and thus regulate the whole community to adapt to the environmental changes,and the extracellular matrix-derived complex resistance mechanisms lead to a certain degree of bacterial resistance to anti-microbial drugs and resistance to immune system,which then makes it difficult for the conventional antimicrobial drugs to effectively eradicate the biofilm-associated infections.The article focuses on the formation of E.coli bio-film,drug resistance mechanisms and treatment aspects and summarizes the progress of research on the novel substitutive therapies against the E.coli biofilms that were developed in recent years,such as phytochemicals,nanomaterials,probiotics and phage therapy,so as to provide theoretical bases for the clinical treatment and the development of novel drug therapies against the E.coli biofilm.

Objective To develop an ultra-high performance liquid chromatography-mass spectrometry method(UPLC-MS/MS)for the determination of nirmatrelvir concentration in mouse plasma.Methods The ACQUITY UPLC system was used in tandem with an API 4000 triple quadrupole mass spectrometer.The analytical column was Waters BEH C18(2.1 mm×5.0 mm,1.7 μm)column,and the mobile phases consisted of water(containing 0.1％formic acid)and methanol(containing 0.1％formic acid)under gradient elution at the flow rate of 0.4 mL·min-1.The column temperature was set at 40 ℃,and the injection volume was 5 μL.Electrospray ionization was used as ion source,and positive multiple reaction monitoring mode was adopted to quantitatively analyze the ionization pairs m/z 500.3→110.3(nirmatrelvir)and m/z 237.3→193.3(carbamazepine).Carbamazepine was employed as an internal standard.Results The linear range of nirmatrelvir was from 10 ng·mL-1 to 2 560 ng·mL-1.For the quality control nirmatrelvir samples,the accuracies of intra-and inter-batch were less than±15％,and the precisions of intra-and inter-batch were lower than 15％.Nirmatrelvir in plasma was stable at room temperature for 24 h and remained stable after three freeze-thaw cycles.The extracted nirmatrelvir solution could be stored at 4℃ for 3 d without any visible change.Conclusion The method was characterized by good specificity,high sensitivity,and appropriate linear range.The methodological validation was in accordance with the 2020 edition of the Chinese Pharmacopoeia and could be applied to the quantitative detection of nirmatrelvir in plasma.

Objective:To apply patent metrics to analyze the distribution, development trends, and characteristics of patents related to orthokeratology lenses for assisted wearing, providing a reference for the research and development of such patents.Methods:Patents related to orthokeratology lenses for assisted wearing were retrieved by computer from the China National Intellectual Property Administration database, incopat, Derwent Innovations Index, Free Patents Online, Organisation Africaine de la Propriété Intellectuelle, and IP Australia. The search timeframe was from the establishing of these databases until March 8, 2024. Patent metrics methods, word frequency analysis, and high-frequency word co-occurrence analysis were used for data analysis.Results:A total of 60 relevant patents were selected. The development of orthokeratology lens-assisted wearing patents began relatively late but has shown a strong growth trend, reaching a peak around 2015. Chinese patents accounted for the largest share (91.7%, 55/60) , with Zhejiang Province, Beijing City, Jiangsu Province, Guangdong Province, and Shanghai City having the highest number of patents. The majority of the applicants were enterprises. The research focus in this field is on mechanical assistance patents for lens wearing, with cutting-edge technologies focusing on monitoring the displacement of lenses relative to the pupil and providing timely feedback and guidance.Conclusions:This study, using patent metrics, word frequency analysis, and high-frequency word co-occurrence analysis, provides a reference for patent applications and product development in orthokeratology lens-assisted wearing in nursing.

Objective:To systematically evaluate the efficacy of vitamin D (VD) in the treatment of male infertility.Methods:Randomized controlled trials (RCT) on male infertility treated with VD alone or in combination were identified and collected from PubMed, Embase, Web of science, CNKI, Wanfang and VIP databases. Patients were divided into experimental group (VD or combination therapy with VD as the main treatment) and control group (placebo treatment). A meta-analysis of the included studies was performed using RevMan5.4 software. The combined effect scale was calculated as the weighted mean difference ( MD) and its 95% CI. Results:Six RCTs with a total of 673 patients were ultimately included, and the study baseline was comparable. Total sperm motility ( MD=6.49, 95% CI: 2.75-10.22, P<0.001) and percentage of forward motile sperm ( MD=5.03, 95% CI: 1.36-8.70, P=0.007) were significantly different between the experimental group and control group. Total sperm count ( MD=5.56, 95% CI: -12.62-23.75, P=0.550), sperm concentration ( MD=-0.30, 95% CI: -4.81-4.21, P=0.890), semen volume ( MD=-0.04, 95% CI: -0.18-0.09, P=0.510) and normal sperm morphology ( MD=0.42, 95% CI: -0.05-0.88, P=0.080) were not significantly different between the experimental group and control group. Conclusion:VD is effective in improving semen quality in the treatment of male infertility. However, due to the limited number of samples included in RCT, clinical trials with larger samples are still needed to further confirm this thesis.

Objective:To explore the relevant risk factors and prognosis of patients with intrahepatic cholangiocarcinoma (ICC) who experienced recurrence within 6 months after surgeryMethods:This retrospective study included a total of 259 patients with ICC a treated at He'nan Provincial People's Hospital and He'nan Cancer Hospital from Jan 2018 to Jan 2020. The clinical and pathological data ,differences between the group with recurrence within 6 months and the group without recurrence within 6 months were compared using the chi-square test. Logistic regression analysis was used to determine the relevant risk factors for recurrence within 6 months. Kaplan-Meier method was used to construct survival and recurrence curves, and survival rates were calculated.Results:The overall survival and recurrence-free survival of patients in the group with recurrence within 6 months were significantly shorter. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery ( P<0.001). Conclusion:The patient population experiencing recurrence within 6 months after ICC surgery has an extremely poor prognosis and possesses a specific tumor microenvironment. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery.

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Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.