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 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.

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.

Objective:This study aims to investigate the relationship between high-risk human papillomavirus (HR-HPV) infection and the composition of vaginal microecology. It will analyze the efficacy of integrated traditional Chinese and Western medicine intervention in treating HR-HPV infection, as well as the effects of this combined approach on vaginal microecology. Additionally, the study seeks to identify new methods to inhibit the malignant progression of cervical intraepithelial lesions.Methods:A prospective study was conducted involving 100 patients with HR-HPV infection who visited the Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from April to June 2023. The participants were randomly divided into a control group and an observation group, with 50 patients in each group using a random number table method. The control group received interferon treatment, while the observation group was treated with a combination of interferon and Yanfukang Lotion. High-throughput DNA sequencing of vaginal secretions was conducted to compare the differences in pre- and post-treatment vaginal microecological composition and the rate of HR-HPV clearance between the two groups. Results:In the observation group, both the diversity index and the abundance of vaginal microecology showed significant improvements compared with the control group, particularly in the abundance of dominant Lactobacillus species. These differences were statistically significant ( R = 0.124, 0.304, 0.030, all P < 0.05). The rates of HR-HPV clearance and overall effective rate (clearance + effective) in the observation group were 44% (22/50) and 68% (34/50), respectively, which were significantly higher than those in the control group [20% (10/50), 32% (16/50), χ2 = 12.98, both P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2 = 1.76, P > 0.05). Conclusion:The combination of interferon and Yanfukang Lotion effectively treats HR-HPV infection by regulating the composition of vaginal microecology. This approach shows considerable efficacy and good safety, indicating its potential for further clinical application.

Objective:This study aims to investigate the relationship between high-risk human papillomavirus (HR-HPV) infection and the composition of vaginal microecology. It will analyze the efficacy of integrated traditional Chinese and Western medicine intervention in treating HR-HPV infection, as well as the effects of this combined approach on vaginal microecology. Additionally, the study seeks to identify new methods to inhibit the malignant progression of cervical intraepithelial lesions.Methods:A prospective study was conducted involving 100 patients with HR-HPV infection who visited the Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from April to June 2023. The participants were randomly divided into a control group and an observation group, with 50 patients in each group using a random number table method. The control group received interferon treatment, while the observation group was treated with a combination of interferon and Yanfukang Lotion. High-throughput DNA sequencing of vaginal secretions was conducted to compare the differences in pre- and post-treatment vaginal microecological composition and the rate of HR-HPV clearance between the two groups. Results:In the observation group, both the diversity index and the abundance of vaginal microecology showed significant improvements compared with the control group, particularly in the abundance of dominant Lactobacillus species. These differences were statistically significant ( R = 0.124, 0.304, 0.030, all P < 0.05). The rates of HR-HPV clearance and overall effective rate (clearance + effective) in the observation group were 44% (22/50) and 68% (34/50), respectively, which were significantly higher than those in the control group [20% (10/50), 32% (16/50), χ2 = 12.98, both P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2 = 1.76, P > 0.05). Conclusion:The combination of interferon and Yanfukang Lotion effectively treats HR-HPV infection by regulating the composition of vaginal microecology. This approach shows considerable efficacy and good safety, indicating its potential for further clinical application.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Objective:To explore multidisciplinary team (MDT) for the treatment of hip fracture in the elderly.Methods:A retrospective analysis was done of the 196 elderly patients who had been admitted to Department of Joint Surgery, Beijing Shijitan Hospital from September 2017 to December 2018 for hip fractures. They were divided into 2 groups depending on whether MDT had been applied or not. In the MDT group of 102 patients, there were 43 males and 59 females with an age of 81.9±8.4 years, and 63 femoral neck fractures and 39 intertrochanteric fractures. In the traditional treatment group of 94 patients, there were 37 males and 57 females with an age of 81.3±8.6 years, and 55 femoral neck fractures and 39 intertrochanteric fractures. The 2 groups were compared in terms of complications and mortality during hospitalization, interval from admission to surgery, total hospital stay, and Harris hip scores at 6 months after surgery.Results:There were no statistically significant differences in general data before surgery between the 2 groups, indicating comparability ( P>0.05). Eighty-four patients (89.4%) in the traditional treatment group and 98 patients (96.1%) in the MDT group underwent surgery, showing no significant difference between the groups ( χ2=3.327, P=0.068). In the patients undergoing surgery in the MDT group, the incidences of postoperative delirium [12.2% (12/98)], pulmonary infection [11.2% (11/98)], cardiogenic disease [13.3%(13/98)], electrolyte disturbance[12.2%(12/98)] and deep venous thrombosis of lower extremity [6.1% (6/98)] were significantly lower, the interval from admission to surgery (1.9 d±0.9 d) and total hospital stay (10.2 d±0.9 d) significantly shorter, and Harris hip scores (81.3±6.2) at 6 months after surgery significantly higher than those in the patients undergoing surgery in the traditional treatment group [31.0%(26/84), 22.6% (19/84), 25.0% (21/84), 28.6% (24/84), 16.7%(14/84); 3.1 d±1.6 d and 14.1 d±6.2 d; 75.4±7.8; respectively] (all P<0.05). Conclusion:In the treatment of hip fracture in the elderly, multidisciplinary team is effective in reducing complications during hospitalization, shortening the interval from admission to surgery and total hospital stay, and promoting functional recovery of the hip.

Objective: To investigate the changes of ³¹P-MRS in denervated skeletal muscle at 7.0 T MR system. Methods: In the experiment group, a total of 18 male Sprague-Dawley rats aged 6-8 weeks old and weighing 200-250 g were obtained. The right posterior femoral nerve were transected, and the proximal stumps were ligated by using 5-0 nylon stitches to preclude spontaneous repair. A sham surgery (incision and exploration of the nerve) was performed at the same time (n=6). Before rat model established and at varying times after initial surgery (3 d, and 1, 2, 4, 6, and 8 weeks). ³¹P-MR spectra of rat quadriceps femoris were acquired on 7.0 T Agilent small animal MR imaging system. We quantified the phosphocreatine (PCr), adenosine triphosphate(β-ATP), and inorganic phosphate (Pi) using Creatine phosphate disodium salt(10 mmol/L) as an external standard. The ratios, include PCr/Pi, Pi/β-ATP, PCr/β-ATP, PCr/(PCr+Pi) and Pi/(PCr+Pi) were quantified in jMRUI. All data were analyzed by one way analysis of variance (ANOVA) with posttest inter-group comparisons using Bonferroni test. Comparative analysis methods between the experimental and control group were performed via independent samples t test. P<0.05 was considered as statistically significance. Results: The average measured concentrations of β-ATP, PCr, and Pi in control groups were (6.654±0.178) μmol/g, (25.656±0.738) μmol/g, and (1.594±0.096) μmol/g, respectively. There were significant statistically differences in β-ATP, PCr, Pi, PCr/Pi, PCr/PCr+Pi,Pi/PCr+Pi between the study and control group(P<0.05) at any measurement time point after denervation. Pi/β-ATP,PCr/β-ATP and pHi in the experimental group significantly statistically differed from those of the control group (all P<0.05)at each time point except on day 3 after operation. The total concentrations of β-ATP and PCr were reduced by 11.5% and 19.7% respectively on day 3. Thereafter, β-ATP and PCr declined rapidly by 63.1% and 68.8% at week 4 respectively, then decreased slowely by 74.0%和82.3% till week 10. The change of PCr/Pi is similar to β-ATP and PCr, but more remarkable. Pi, Pi/PCr+Pi, Pi/ATP showed a progressively increase till week 10. The intra-cellular pH (pHi) of normal rat muscles was 7.033±0.017, While the pHi gently in experiment rat muscles decreased during the entire experiment. Conclusion ³¹P-MRS with 7.0 T can quantify the temporal changes of energy metabolism and pHi in normal and denervated rat muscles. It shows that the dysfunction of energy metabolism are progressive with time and that they begin within a short period following the nerve section, the change of β-ATP, PCr, PCr/Pi take place primarily within 4 weeks after denervation. β-ATP, PCr, and PCr/Pi may be potential biomarkers of energy metabolism in the evaluation of denervated muscle atrophy.

Objective To investigate the effects of tranexamic acid (TXA) on perioperative blood loss,D-Dimer and fibrinogen (FIB) in total knee arthroplasty (TKA).Methods A prospective study,from December 2016 to November 2017 patients with end-stage knee osteoarthritis underwent unilateral TKA were randomly divided into two groups.Patients in treatment group received two doses of 15 mg/kg TXA by intravenous inffusion 1 hour pre-operation and before the release of tourniquet;the control group was replaced with the same amount of saline.The preoperative and 3 days post-operation hemoglobin,hematocrit value,drainage,blood transfusion were recorded.The D-Dimer and FIB were dynamically monitored before operation and 1,3,7,14 d after the operation.And there were also observations for whether they had deep vein thrombosis and both lower limbs of all patients were examined by the color Doppler ultrasonography 14 days after operation.Results The drainage and the total blood loss in treatment group was significantly less than in control group (P ＜ 0.01,P ＜ 0.05).The volume of both allogeneic and autologous blood transfusion in treatment group were significantly less than those in the control group (P ＜0.01).The ratio of allogenic blood transfusion was 14.6％ (6/41) in treatment group,38.1％ (16/42) in control group (P ＜ 0.01).D-dimer at 1,3d post-operation in treatment group was significantly lower than that in the control group (P ＜0.05),but the difference was getting smaller at 7,14d post-operation (P ＞0.05).FIB at any time point between the two groups was no significant difference (P ＞ 0.05).There was no symptomatic deep venous thrombosis (DVT) in all of the three groups within 14 days.Conclusions The TXA infused intravenous can significantly decrease drainage,the total blood loss and blood transfusion without increasing risk for DVT in TKA.but early post-operation TXA could affect the level of D-dimer,thus affecting the value of early warning of DVT.

Objective To discuss the safety and short-term efficacy of MR-guided focused ultrasound surgery (MRgFUS) for pain palliation of bone metastases patients.Methods Fourteen patients with painful bone metastases were recruited in this prospective study.The treating efficacy was characterized by numerical rating scale (NRS),the brief pain inventory quality of life (BPI-QOL) survey,and Karnosky performance status scale (KPS).Adverse events occurred pre-and post-treatment were analyzed.Normal distributed statistics was analyzed by using paired-samples t test or Wilcoxon rank sum test.Results Fourteen patients were treated with MRgFUS,2 patients dropped out of the study.The NRS ratings are 6.50(4.00),5.00 (5.25),2.50(5.00),2.50(4.75),2.00 (6.00) for pre-treatment,one week,one month,two months,and three months,respectively.Such variances of NRS ratings were statistically significant (Z=-2.773,-2.740,-2.769,-2.675;P＜0.05).The BPI-QOL ratings were (42.42± 8.27),(30.67 ± 12.29),(29.17±15.38),(29.92± 17.67) and (35.67± 19.28),respectively.The BPI-QOL ratings decreased in the first two months after the treatment which is statistically significant (t=3.231,2.820 and 2.453;P＜0.05);whereas for the third month,the BPI-QOL rating was statistically insignificant compared with the one before the treatment (P＞0.05).The KPS ratings were 80(28),80(20),65(45) for pre-treatment,one week and three months after treatment,respectively.Three months after the treatment,the KPS ratings decreased which was statistically significant compared with the one before the treatment (Z=-2.204,P＜0.05).After the treatment,one patient developed deep venous thrombosis,three patients reported lower extremities numbness,two patients had soft tissue edema around the lesions.Conclusions MRgFUS is effective for short-term pain palliation of bone metastases.Such noninvasive technique is safe and can improve patients' living condition.