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.

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 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 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.

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.

Objective:To research the quality control and testing methods of polysomnography and to ensure its safe and effective performance.Methods:A quality control testing method was designed for the main indicators of EEG signal,EMG signal,ECG signal,and pulse oxygen saturation of polysomnography.In August 2023,two polysomnography instruments of the same brand and different models(marked as Test Equipment A and Test Equipment B)in clinical use in Daping Hospital,Army Medical University were selected.The quality control testing of polysomnography instrument was conducted by using electroencephalogram calibration instrument and vital sign simulator to evaluate the reliability of the performance of polysomnography.Results:A quality control testing method was developed for quality control testing of polysomnography aiming at the repeatability of the indicated values of EEG signals,EMG signals,ECG signals,and pulse oxygen saturation of polysomnography.Except for the output value of 2 mV of the voltage measurement simulator of test equipment B,the relative error of the recorded data was-11%,and the parameters were out of tolerance,and the rest of the test data of test equipment A and test equipment B met the maximum limit output value of the national metrology verification regulations and the technical requirements of the equipment manufacturer.Conclusion:The quality control detection method of polysomnography can evaluate the performance parameters of the selected testing equipment A and testing equipment B,and provide technical support for the quality control detection and safe use of such equipment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.