OBJECTIVE To optimize the extraction process of flavonoids from Potentilla discolor .METHODS Deep eutectic solvents （DESs） were used as the extraction solvent to prepare test sample solutions. The contents of rutin， quercitrin， and kaempferol were determined by ultra-performance liquid chromatography. The analytic hierarchy process combined with the criteria importance through intercriteria correlation weighting method was employed to assign comprehensive weights to the contents of the three flavonoids， and calculate the comprehensive score. The optimal DESs were screened based on the comprehensive score.Mean while， using the comprehensive score as the response variable and the liquid-to-solid ratio， ultrasonic time， and urltrasonic temperature as the influencing factors， the extraction technology of flavonoids from P.discolor was optimized by Box-Behnken response surface methodology and subsequently validated.RESULTS The comprehensive weight coefficients of rutin， quercitrin， and kaempferol were 0.646 7， 0.207 5， and 0.145 8， respectively. The optimal DESs were choline chloride-lactic acid （molar ratio 1∶4） with a water content of 40%. The optimal extraction conditions were determined as follows： liquid-to-solid ratio of 25∶1， ultrasonic time of 40 min， and ultrasonic temperature of 50 ℃. The validation results showed that the average comprehensive score of three batches of samples was 99.28， with an RSD of 0.54% （ n ＝3）.CONCLUSIONS The optimal extraction technology of flavonoids from P. discolor based on DESs obtained in this study was stable and feasible.

OBJECTIVE To provide guidance for pharmaceutical care in patients with severe Cryptococcus gattii infections.METHODS Clinical pharmacists participated in the diagnosis and treatment of a male patient with disseminated Cryptococcus gattii infection （involving the lungs and central nervous system）. Given the patient’s poor response to initial therapy， the clinical pharmacists， based on antimicrobial susceptibility test results， recommended voriconazole as an alternative azole. In response to refractory hypokalemia caused by liposomal amphotericin B， the clinical pharmacists assisted the physician in developing an intensive potassium replacement regimen. Regarding the interaction between voriconazole and nifedipine， the clinical pharmacists proactively identified the risk and intensified monitoring of the patient’s blood pressure. In response to the onset of hepatitis C during treatment， the clinical pharmacists thoroughly weighed the priority of infection treatment and recommended temporarily postponing antiviral therapy for hepatitis C. For the individualized use of voriconazole， the clinical pharmacists repeatedly performed therapeutic drug monitoring （TDM）. Regarding the patient’s poor lesion resolution， the clinical pharmacists participated in multidisciplinary team discussions to clarify the indications for surgery.RESULTS The physician adopted the clinical pharmacists’ recommendations. Following pharmacological treatment and surgical intervention， the patient’s condition stabilized， and he was discharged while still on medication.CONCLUSIONS For severe Cryptococcus gattii infections， clinical pharmacists should focus on pathogen characteristics， strengthen adverse reaction management， pay close attention to drug interactions， conduct TDM， and actively participate in multidisciplinary team collaboration to ensure the safety and efficacy of patient treatment.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective : To investigate the association between single nucleotide polymorphism(SNP) of PROS1 gene and recurrent spontaneous abortion(RSA) in Baotou Han population. Methods : 158 RSA patients and 158 control subjects were selected as the study subjects, and the activities of protein S, protein C and antithrombin-Ⅲ were measured. The rs13062355, rs6441600 and rs12634349 loci of PROS1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Non-conditional Logistic regression was used to analyze the correlation between three SNPs of PROS1 gene and the risk of RSA. Results : The protein S and antithrombin-Ⅲ activities of RSA patients decreased significantly(P<0.05). PROS1 SNP rs13062355 was associated with the risk of RSA under the dominant model: compared with genotype TT, patients with CT+CC genotypes had a reduced risk of RSA(OR=0.398, 95%CI: 0.249-0.638); SNP rs6441600 and rs12634349 were not associated with the risk of RSA(P>0.05). In the haplotypes constructed by PROS1 rs13062355, rs6441600 and rs12634349, Haplotype C-C-C was statistically different between the two groups(P<0.05). The third-order interaction model rs13062355-rs6441600-rs12634349 was associated with the risk of RSA. Conclusion PROS1 SNP rs13062355 may be associated with the risk of RSA in Han women in Baotou area. Haplotype C-C-C of PROS1 rs13062355, rs6441600 and rs12634349 reduces the risk of RSA. The third-order model rs13062355-rs6441600-rs12634349 interaction has a synergistic effect on the occurrence of RSA.

Objective To explore the prevalence of 9 respiratory pathogens from March 2023 to February 2024,as well as the detection efficiency of various methods for pathogens.Methods A retrospective analysis was conducted on the detection of 9 pathogens in 38 948 patients who first presented with respiratory symp-toms from March 2023 to February 2024,as well as the detection efficacy of nucleic acid,antigen,antibody and other methods.Results Firstly,among 38 948 patients,a total of 8 345 cases(21.43%)were detected with at least one pathogen,of which 8 158 cases(20.95%)were detected with only one pathogen,and 187 cases(2.29%,187/8 158)were detected with two or more pathogens.The top three detection rates were SARS-CoV-2(20.37%),mycoplasma pneumoniae(MP,15.58%)and influenza A virus(IVA,10.79%).Secondly,among patients who detected at least one of the nine pathogens,the detection rate was 24.94%in autumn,21.45%in spring,18.54%in summer,and 19.22%in winter,and the difference in detection rates between the four seasons was statistically significant(P<0.001).Thirdly,except for the relatively high detection rates of SARS-CoV-2 in spring(51.24%)and summer(37.31%),and the highest detection rate of IVB in winter(11.28%),the detection rates of other pathogens were highest in autumn.Fourthly,there was a statistically significant difference in the total detection rates among the children group(31.83%),the youth group(12.48%),the middle-aged group(10.70%),and the elderly group(12.43%)(P<0.001).The detection rates of 7 pathogens,including MP,IVA,Influenza B virus(IVB),syncytial virus,CP,adenovirus,and parain-fluenza virus type 1,were highest in children,and there was a statistically significant difference in comparison between different age groups(P<0.05).The detection rate of SARS-CoV-2 in the children group(3.45%)was lower than that in other age groups(30.90%,29.09%,32.16%,P<0.001).There was no statistically significant difference in HPIV-3 between different age groups(P=0.478).Fifthly,there was no significant difference in overall detection rate between male and female(P>0.05).However,the detection rates of MP and CP in female were higher than those in male(P<0.05),while IVA in male was slightly higher than that in female(P=0.014).There were no significant differences in the detection rate of other 6 pathogens between female and male(P>0.05).Sixthly,the detection rate of MP antigen was lower than that of MP nucleic acid detection(P<0.001),and the detection rate of MP antibody detection was lower than that of MP nucleic acid detection(P<0.001).The detection rate of MP antibody detection increased significantly with the extension of time from initial symptoms to medical treatment(P<0.001).Seventhly,the detection rates of antigen of IVA,IVB,RSV and ADV were significantly lower than those of the corresponding nucleic acid(P<0.001),and the detection rates of nucleic acid testing for 4 kinds of pathogen was about 5 times that of the correspond-ing antigen testing(4.75-6.25 times).And the consistency of the detection rate between antigen detection and nucleic acid detection was poor(Kappa=0.046-0.239).Conclusion The prevalence of common respir-atory pathogens from March 2023 to February 2024 exhibits certain characteristics.Moreover,the detection ef-ficiency of different methods for pathogens varies greatly,and appropriate detection methods should be select-ed based on a thorough understanding of their performance.

Objective To explore the acceptability of routine biochemical test results for serum samples with varying degrees of chylous high triglyceride(TG).Methods Blood samples of 69 patients with different degrees of lipids were collected,including 33 patients with mild to moderate lipids(1.7 mmol/L≤TG<5.6 mmol/L)and 36 patients with severe lipids(TG≥5.6 mmol/L).Twenty-nine biochemical tests were detected before and after high-speed centrifugation.The result acceptability before high speed centrifugation of serum was compared with the results after high speed centrifugation as the gold standard[TG and total cholesterol(TC)before centrifugation].The acceptable criteria were subject to the following three conditions at the same time.Firstly,correlation coefficient(R2)was greater than or equal to 0.95.Secondly,the slope of linear re-gression equation was 1.00±0.05.Thirdly,for the same index,the number of samples whose result bias be-fore and after centrifugation was less than 1/2 total allowable error(TEa)in more than 90%of the total sam-ple numbers.Results Firstly,in the mild to moderate lipemia group,22 tests met the criteria,7 tests did not,including total protein(TP),albumin(ALB),TG,aspartate aminotransferase(AST),carbon dioxide(CO2),α-L-fucosidase(AFU),lactate dehydrogenase(LDH)(bias<10%),and the coincidence rate was 75.9%.In the severe lipemia group,12 tests met the criteria,17 tests did not,including pre-albumin(PA),AFU,γ-glu-tamyltransferase(γ-GT),LDH,AST,TC,direct bilirubin(DBIL),CO2,5'-nucleotidase(5'-NT),small and low-density lipoprotein cholesterol(sd-LDL-C),high density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),adenosine deaminase(ADA),cystatin C(CysC),glycosylated albumin(GA),total bilirubin(TBIL)(bias>10%),the coincidence rate was 41.4%,and there was a statistically sig-nificant difference in the coincidence rate between the two groups(P<0.05).Secondly,there was no statisti-cally significant difference in the acceptability of results between continuous monitoring method and endpoint method detection methods(P>0.05).Conclusion Most test results of direct determination with mild or moderate lipemia samples are acceptable,and the bias of unacceptable tests is small(<10%),so it is recom-mended to issue a test report without further sample treatment.However,due to the large number of unacceptable tests and larger bias(>10%),severe lipemia samples should be determined after high-speed centrifugation.

Rolling manipulation is one of the swing techniques with strong operational skills in massage therapy. This article summarized the biomechanical parameters and mechanism of the massage operation from multiple perspectives, including three-dimensional motion, force trajectory, dynamic parameters, force effect relationship, and mechanism. It is found that the massage operation could exert force in the vertical and horizontal directions of the body surface, and the movement trajectories of the front and back were generally symmetrical. The anterior force was approximately three times the retraction force, and the brachioradialis, pectoralis major, triceps, and deltoids were the main muscles that could exert force during manual manipulation. The method can have effects on hemodynamics, cellular anti-inflammatory effects, and improve the physiological function of tissues and organs. However, there is currently a lack of objective and unified norms and standards for the specific strength, frequency, and specific parameter combinations of massage methods, so the further improvement is still needed.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

In the context of an aging population, diabetes has emerged as a significant public health challenge.However, compared to the extensive research on target organs such as the cardiovascular, nervous, and renal systems, the impact of diabetes on the skeletal system has been underestimated.The pathological microenvironment of diabetes and systemic internal environment disorders harm bones by affecting bone density, disrupting bone microstructure, interfering with the bone mineralization process, and reducing the quality of bone collagen, which leads to the development of osteoporosis.Therefore, maintaining bone health should be an important component of comprehensive diabetes management.This review aims to provide an overview of the pathological characteristics, mechanisms, and treatment strategies for osteoporosis in both type 1 and type 2 diabetes, serving as a reference for bone health management in diabetic patients.

Objective To optimized the extraction process of the"Honghuangbai"gel and to establish the content determination method of the gel.Methods The contents of salidroside,berberine hydrochloride and 1,4-bis[4-(glucose-oxy)benzyl]-2-isobutyl malate in"honghuangbai"extract were determined by HPLC with gradient elution;the content of total polysaccharide was determined by anthrone-sulfuric acid method.AHP-CRITIC composite weighting method was used to calculate the weight coefficient of 4 indicators,and the comprehensive score was taken as the evaluation index.Combined with L9(34)orthogonal experiment design,the effects of solid-liquid ratio,extraction time and times on the extraction process of"honghuangbai"gel were investigated,and the optimal extraction process was selected and verified.The method for the determination of 4 index components in the gel was established and the methodology was investigated.Results The optimal solid-liquid ratio was 1∶45,the optimal extraction time was 2 h and the optimal extraction times was twice.The linear relationships of the four indexes were good in their respective linear ranges,with R2＞0.999 0.The average recoveries were 98.67％～102.09％,and RSD was 0.77％～3.17％.Good precision,repeatability and stability,RSD≤2.28％.Conclusion The optimal extraction process of"honghuangbai"gel optimized by AHP-CRITIC combined with orthogonal test is stable and economical.The method of the gel content determination is feasible and the result is reliable,which provides experimental basis for the establishment of the quality standard of the gel.