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.

ObjectiveTo analyze the trend of lung cancer incidence in Fenghua District, Ningbo City of Zhejiang Province from 2009 to 2023, and to estimate the age-period- cohort effects of incidence rate, so as to provide scientific basis for the formulation of lung cancer prevention and control measures in Fenghua District. MethodsJoinpoint software was utilized to analyze the trends and calculate the average annual percentage change (AAPC) of lung cancer incidence based on the tumor incidence surveillance data from Fenghua District, 2009‒2023. The age-period-cohort (APC) model for lung cancer incidence was analyzed using STATA 17.0 software, and net drift and local drift of lung cancer incidence rates were analyzed using online analytical tools. ResultsThe incidence of lung cancer in Fenghua District showed an overall upward trend from 2009 to 2023, with the standardized incidence rate increasing from 45.05/100 000 in 2009 to 108.20/100 000 in 2023(AAPC=7.05%, P<0.05). The increase in the standardized incidence rate for females (AAPC=12.72%, P<0.05) was higher than that for males (AAPC=2.97%, P<0.05). The overall net drift in lung cancer incidence for residents of Fenghua District was 11.71%, with the net drift for females (16.54%) being higher than that for males (6.64%). The local drift in lung cancer incidence among different age groups ranged from -3.37% to 35.18%. The results of APC model showed that the risk of lung cancer incidence increased and then decreased with age, with the highest age effect coefficient observed in the 65‒69 years age group at 1.08. The period effect showed a gradually increasing trend in lung cancer incidence risk with the progression of time, and the period effect coefficient in 2019‒2023 (0.46) was higher than that in 2009‒2013 (-0.39), increasing by 217.95%. The cohort effect coefficient showed a trend of first decreasing and then increasing with the expansion of the birth cohort, in which the lowest cohort effect coefficient was -1.07 observed in the birth cohort of 1964‒1968 and the highest cohort effect coefficient was 1.77 in the birth cohort of 1924‒1928. ConclusionThe incidence of lung cancer in Fenghua District shows an upward trend from 2009 to 2023, with a higher increase in incidence rates among females than that in males. The risk of lung cancer incidence exists a trend of increasing and then decreasing with age growth. With the progression of time, the risk of lung cancer incidence shows a gradually increasing trend. However, with the expansion the birth cohort, the risk of lung cancer incidence demonstrates a trend of first decreasing and then increasing.

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 To investigate the intervention of Chinese herb Shengjiang San(SJS)for the imbal-ances of serum Th1/Th2 cells and related regulatory factors in sepsis patients. Methods Fifty-five sepsis patients were randomly divided into two groups:conventional treatment group of 27 cases and SJS group of 28 cases. Nine cases of healthy volunteers were enrolled as control group in the study. Cases of conventional group were treated with western medicine only and cases of SJS group were treated with both western medicine and Chinese herb SJS (100 mL twice one day). The therapy course of both groups was 3 days. Score of Chinese medical syndromes ,se-rum level of leukocyte count,C reactive protein(CRP)and procalcitonin(PCT),serum T-bet,GATA-3,Th1&Th2 cells in the proportion of whole CD4+Th cells and Th1/Th2 ratio were compared respectively in each group be-fore and after treatment. Results There were significant differences between SJS group and conventional group in score of Chinese medical syndromes,serum level of leukocyte count,T-bet,GATA-3,Th1&Th2 cells in the pro-portion of whole CD4+Th cells and Th1/Th2 ratio(P<0.05 or P<0.01). There were no significant differences be-tween the two groups in serum level of CRP,PCT and GATA3. Compared with control group,there were signifi-cant differences in all indicators except GATA3 of the two groups(P<0.01). Conclusion Chinese herb Shengji-ang San has an effective benefits to Chinese medical syndromes,inflammatory reaction,the imbalance of serum Th1/T2 and related regulatory factors(T-bet&GATA-3)in sepsis patients.

Objective To analyze the mutation status of K‐ras gene in colorectal cancer patients ,further more ,to provide guid‐ance for personalized therapy for colorectal cancer .Methods Nested and COLD‐PCR were used to detect the K‐ras mutations in 560 patients with colorectal cancer .Results In 560 colorectal cancer patients ,the total positive rate of K‐ras gene mutations was 27 .08% ,the mutation rate was 0 in 128 plasma samples and it was 27 .08% in 432 tissue samples .The mutate sites were G12S , G12C ,G12D ,G12A ,G12V ,G13R ,G13C ,G13D ,Q61K ,Q61L ,there were significant differences existed in different samples (P <0 .000 1) ;the mutation rate of 362 male patients was 20 .44% and the types of mutation include G12S ,G12C ,G12D ,G12V ,G13R , G13C ,G13D ,Q61K and Q61L .The mutation frequency was 21 .72% in 198 female patients ,the mutation points were G12S ,G12C , G12D ,G12A ,G12V ,G13R and G13D .There were no significant difference between different sex (P= 0 .722 7) ;the mutation fre‐quency was 20% in 80 youth patients including G12S ,G12C ,G12D ,G12V ,G13D and the mutation rate was 33 .07% in 127 middle age patients ,the points of mutation were G12S ,G12D ,G12A ,G12V ,G13R ,G13C ,G13D ,Q61K ,Q61L ,the mutation frequency was 16 .71% in 353 old age patients ,the types of mutation include G12C ,G12D ,G12V ,G13R ,G13D ,the difference was significant a‐mong different age patients (P= 0 .000 5) .Conclusion The total rate of mutations is 27 .08% in 560 colorectal cancer patients ,and the main points of mutation is G12D ,G12V ,G13D .There are significant differences in different type of samples as well as in differ‐ent ages ,but no statistical significance in different sex patients .

Professor HE Tianyou's unique understanding and treatment characteristics for intractahle facial paralysis are introduced. In clinical practice professor HE highly values acupoint selection and manipulation application, and integrates Chinese and western medicine to flexibly choose acupoints and formulate prescriptions according to syndrome differentiation and location differentiation, besides, he creates several specialized manipulation methods including "tug-of war opposite acupuncture method" and "tractive flash cupping". Based on strengthening body and dredging collaterals. more attention is given on stimulation to local paralyzed facial nerves; meanwhile acupuncture and medication are combined to improve clinical efficacy. During the treatment, the important role of psychological counseling on patient's anxiety is emphasized, and comprehensive treatment is given physically and psychologically in order to achieve the purpose of total rehabilitation.
Acupuncture Points ; Acupuncture Therapy ; Adult ; Drugs, Chinese Herbal ; administration & dosage ; Facial Paralysis ; drug therapy ; therapy ; Female ; Humans ; Medicine

Aim To investigate the inhibitory effects of urocortin2 (UCN2) on ventral tegmental area (VTA) nervous activity of morphine addiction rats and the mechanism. Methods Morphine addiction rats and the microiontophoresis method were used to observe the effects of UCN2 on VTA neuron′s spontaneous dis-charge changing rule, as well as the inhibitory effects of UCN2 on DA neuron′s cluster spontaneous dis-charge, to identify UCN2 and DA on the same VTA neuron. Morever, the inhibitor of corticotropin-regula-ting factor′s receptor ( CRF-2 R ) and the blocker of protein kinase A ( PKA ) , AST-2 B and H89 , were used to investigate the effects of UCN2 on VTA neuron′s of morphine addiction rats. Results UCN2 could inhibit the firing rate 82% (31/38) of the tested VTA neuron ( P<0. 01 ) , the discharge frequency changed from (20. 89 ± 2. 86) Hz to (13. 66 ± 3. 93) Hz (P<0. 01). Further, the inhibitor of PKA, AST-2B and H89 could ablolish the inhibitory effects of UCN2 . Morever, the excitatory firing of VTA neurons was at-tenuated by addition of UCN2 , while AST application could inhibit the UCN2′s inhibitory effects. Conclu-sion UCN2 could regulate the effects of VTA via PKA pathway and may thereby contribute to the improvement of drug addiction.

Objective To investigate the effect of high mobility group box-1 protein (HMGB1) on inter-leukin-2 (1L-2) and interleukin-2 receptor α (IL-2α) expressions in human T lymphocytes and its potential regulat-ing mechanism in vitro. Method Human T lymphocytes were isolated and suspended, the cells were cultured with 20 μg/mL phytohemagglutinin (PHA) in 5% CO_2 at 37 ℃, recombinant human HMGB1 (rhHMGB1, 0, 10, 100, 1000 ng/mL) was added with the PHA and cultures were centrifuged at 12 and 48 hours for cell collect-ing. Reverse transcription polymerase chain reaction (RT-PCR) amplification was perfomed to determine gene ex-pressions of IL-2, IL-2Rα. IL-2, sIL-2R protein levels in cell culture supematants were measured by ELIZA. Re-sults After coincubated with rhHMGB1 (10, 100, and 1000 ng/mL) for 12 hours, IL-2 levels in cell culture su-pernatants respectively were 0 . 064 ± 0. 017 μg/L, 0.076±0.033 μg/L, and 0.061 ±0.02 μg/L, which were significantly higher compared with the untreated cells (0.045±0.011 μg/L, P < 0.05 or P < 0.01). Mean-while, IL-2 mRNA expression was markedly up-regulated following rhHMGB1 stimulation in various doses (F = 4.6872, P < 0.01). At 48 bourn, however, both IL-2 mRNA expression and protein production tended to de-crease along with an increased dose of dd-IMGB1 stimulationn. IL-2/sIL-2R ratio in 1000 ng/mL rhHMGB1 was markedly lower than that in 10 ng/ml rhHMGB1 (0.036±0.015 vs.0.055±0.017, P <0.05), together with down-regulation of IL-2Rα mRNA expression(P <0.01). Conclusions These data indieated that HMGBI could marked influence the IL-2/IL-2R expression in human T lymphocytes. With the increase in stimulating doses and prolongation of time, HMGBI might down-regulate T cell-mediated immune response of human lymphocytes.