To analyze the investigation and disposal of an H5N6 human infection with animal derived influenza epidemic in Quanzhou City in 2024, and provide reference for the control and prevention of animal derived influenza epidemics in future.According to Technical Guidelines for Control and Prevention of Human infected with Zoonotic Influenza Viruses (Trial), we investigated the diagnosis and treatment of the case, suspected exposure, infection sources and routes, by the method of field epidemiological investigation. The case, close contacts, and relevant environmental samples were collected for nucleic acid testing and gene sequencing. A nasopharyngeal carcinoma patient who rapidly progressed to severe pneumonia and died of multiple organ failure after being diagnosed with H5N6. The H5N6 virus nucleic acid test results of 5 close contacts and 37 suspected exposed individuals were all negative, and no second-generation cases occurred. Through on-site investigation and genetic sequencing analysis, it is highly likely that the source of infection is the outdoor environment of free range poultry contaminated with H5N6 virus in the vicinity of the patient's home.Patients with nasopharyngeal carcinoma or other immune restricted diseases should take personal protective measures, stay away from poultry and livestock breeding and trading places, and avoid close contact with poultry or other animals as much as possible. We should strengthen the training of management personnel of third-party testing institutions, enhance the work of thematic risk assessment and the application of risk assessment results,and expand the scope of monitoring human infected with zoonotic influenza viruses in breeding farms, live poultry markets, and migratory bird habitats.

Objective To investigate the relationship between cerebrospinal fluid albumin/serum albumin(C-ALB/S-Alb)and the systemic immune inflammatory index(SII)and postoperative delirium(POD)in elderly patients with general anesthesia combined with epidural anesthesia.Methods Elderly patients who un-derwent elective hip replacement surgery and received general anesthesia combined with epidural anesthesia in this hospital from October 2023 to June 2024 were selected.According to the assessment results of the Chi-nese version of the 3-Minute Delirium Diagnostic Scale(3D-CAM),the patients were divided into the POD group(68 cases)and the non-POD group(76 cases).The general information of the patients was collected,the cerebrospinal fluid and venous blood specimens were detected.The levels of cerebrospinal fluid albumin(C-Alb),serum albumin(S-Alb),α-synuclein(α-syn),β-amyloid protein(Aβ)1-42,Aβ1-40,total Tau protein(t-Tau),phosphorylated Tau protein(p-Tau)were detected by enzyme-linked immunosorbent assay(ELISA).The neutrophil count,platelet count and lymphocyte count of the patients were detected by the fully automatic blood analyzer,and the SII was calculated.Results Compared with the non-POD group,the levels of C-Alb,α-syn,t-Tau,p-tau,SII and C-Alb/S-Alb in the POD group increased,while Aβ1-42 and Aβ1-40 were significantly decreased,and the differences were statistically significant(P＜0.05).C-Alb,t-Tau,SII and C-Alb/S-Alb were all independent risk factors for the occurrence of POD.The results of the receiver operating characteristic(ROC)curve analysis showed that the areas under the curve(AUC)of the ROC curves of SII,t-Tau,C-Alb,C-Alb/S-Alb and C-Alb/S-Alb combined with SII for predicting delirium were 0.824,0.818,0.723,0.862 and 0.926,respectively.The AUC predicted by C-Alb/S-Alb combined with SII was the highest(all P＜0.05).Conclusion High SII and C-Alb/S-Alb are independent risk factors for POD occurrence in eld-erly patients with general anesthesia combined with epidural anesthesia.Both have good predictive efficacy for POD,and the combined use has better predictive efficacy.

OBJECTIVE To establish HPLC fingerprints of three drying processes(Atmospheric pressure drying,Decompression drying,Freeze-drying)of Danggui Buxue granules,and combine them with antioxidant tests to determine the optimal drying process and main active components of Danggui Buxue granules.METHODS The fingerprints of multiple batches of Danggui Buxue granules were established by HPLC;the"Fingerprint Similarity Evaluation System of Traditional Chinese Medicine Chromatogram"was used to evaluate the similarity;Hierarchical Cluster Analysis(HCA)and Principal Component Analysis(PCA)were used to characterize the different drying processes of Danggui Buxue granules;evaluate the antioxidant activity of Danggui Buxue granules in different drying processes using 1,1-diphenyl-2-picrylhydrazy(DPPH)and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt(ABTS)free radical scavenging method;the spectrum-effect relationship between Danggui Buxue granules fingerprint and antioxi-dant activity was analyzed by grey correlation degree and Pearson,Spearman,Kendall's tau-b correlation analysis methods.RE-SULTS The results of fingerprint showed that there were 16 common peaks in 30 batches of Danggui Buxue granules,and 6 of them were identified by comparison.The results of Cluster Analysis and Principal Component Analysis showed that 30 batches of Danggui buxue granules were divided into 3 categories,and the difference between the groups of atmospheric pressure drying was the least.The results of oxidation test showed that different drying processes of Danggui Buxue granules had good antioxidant activity,and the atmos-pheric pressure drying had the lowest IC50 and the strongest antioxidant activity.Finally,combining the results of gray correlation anal-ysis and correlation analysis,the compounds F2,F10,F13(calycosin),F15(formononetin),F16 might be important characteristic peaks reflecting the antioxidant activity of Danggui Buxue granules.CONCLUSION Compared with other drying processes,atmos-pheric pressure drying has higher batch consistency and stronger antioxidant activity,and can be used as the preferred drying process for Danggui Buxue granules,and components 2,10,13,15 and 16 are the main active ingredients for Danggui Buxue granules to exert antioxidant effects.

OBJECTIVE To establish HPLC fingerprints of three drying processes(Atmospheric pressure drying,Decompression drying,Freeze-drying)of Danggui Buxue granules,and combine them with antioxidant tests to determine the optimal drying process and main active components of Danggui Buxue granules.METHODS The fingerprints of multiple batches of Danggui Buxue granules were established by HPLC;the"Fingerprint Similarity Evaluation System of Traditional Chinese Medicine Chromatogram"was used to evaluate the similarity;Hierarchical Cluster Analysis(HCA)and Principal Component Analysis(PCA)were used to characterize the different drying processes of Danggui Buxue granules;evaluate the antioxidant activity of Danggui Buxue granules in different drying processes using 1,1-diphenyl-2-picrylhydrazy(DPPH)and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt(ABTS)free radical scavenging method;the spectrum-effect relationship between Danggui Buxue granules fingerprint and antioxi-dant activity was analyzed by grey correlation degree and Pearson,Spearman,Kendall's tau-b correlation analysis methods.RE-SULTS The results of fingerprint showed that there were 16 common peaks in 30 batches of Danggui Buxue granules,and 6 of them were identified by comparison.The results of Cluster Analysis and Principal Component Analysis showed that 30 batches of Danggui buxue granules were divided into 3 categories,and the difference between the groups of atmospheric pressure drying was the least.The results of oxidation test showed that different drying processes of Danggui Buxue granules had good antioxidant activity,and the atmos-pheric pressure drying had the lowest IC50 and the strongest antioxidant activity.Finally,combining the results of gray correlation anal-ysis and correlation analysis,the compounds F2,F10,F13(calycosin),F15(formononetin),F16 might be important characteristic peaks reflecting the antioxidant activity of Danggui Buxue granules.CONCLUSION Compared with other drying processes,atmos-pheric pressure drying has higher batch consistency and stronger antioxidant activity,and can be used as the preferred drying process for Danggui Buxue granules,and components 2,10,13,15 and 16 are the main active ingredients for Danggui Buxue granules to exert antioxidant effects.

Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.

Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.

Objective:To evaluate the potential of 177Lu-prostate specific membrane antigen (PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and compare it with 177Lu-PSMA-I&T. Methods:177Lu-PSMA-3Q was prepared and the quality control and stability testing were performed. Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were conducted in normal BALB/c mice and 22Rv1 tumor-bearing mice. SPECT imaging was performed on 2 patients (60 and 76 years old) with mCRPC from Chinese PLA General Hospital at 24, 72, and 120 h after injection of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T ((7.40±0.74) GBq). Data were analyzed by using independent-sample t test. Results:177Lu-PSMA-3Q was prepared with the total activity of 74 GBq, the yield rate of 95% (uncorrected), and the radiochemical purity was still above 95% after 168 h at room temperature. The distribution half-lives of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were (0.75±0.22) and (0.86±0.19) min, and the clearance half-lives were (24.74±3.77) and (29.53±3.42) min. Biodistribution of normal mice showed that the uptake values in the liver, lungs, and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177Lu-PSMA-I&T ( t values: 4.24-8.36, all P<0.05). The tumor uptake of 177Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177Lu-PSMA-I&T ((0.856±0.183) vs (0.579±0.126) percentage activity of injection dose per gram of tissue (%ID/g); t=2.78, P=0.024) in 22Rv1 tumor-bearing mice. The rapid clearance pattern resulted in a higher tumor/muscle (T/M) ratio for 177Lu-PSMA-3Q (99.604±11.106), which was significantly higher than that for 177Lu-PSMA-I&T (45.078±10.444; t=7.80, P<0.001). According to SPECT imaging of patients with mCRPC, the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h, with significant difference ( t=7.62, P=0.002). Conclusion:177Lu-PSMA-3Q is easy to label, and has high yield and radiochemical purity, good stability, excellent biological performance, good targeting ability in patients, longer retention time, and fast background clearance rate, which is an ideal prostate cancer treatment drug targeting PSMA.

Objective:To observe the clinical effect of tranexamic acid radiofrequency introduction combined with Q-switched laser comprehensive treatment of moderate to severe melasma.Methods:From December 2019 to September 2021, ninety-six female patients with melasma [age 24-59 years old, average age (37.8±6.0) years old] were admitted to the Plastic and Aesthetic Department of the First Affiliated Hospital of Henan University of Chinese Medicine. They were divided into the Q-switched laser group and the combined group by random number table method, with 48 cases respectively. The Q-switched laser group received Q-switched laser therapy, while the combined group received tranexamic acid radiofrequency introduction combined with Q-switched laser comprehensive therapy. The melasma area and severity index (MASI) scores were compared between the two groups before and after treatment. The clinical efficacy, adverse reactions and recurrence rates of the two groups were compared.Results:The MASI scores of the Q-switched laser group and the combined treatment group were (28.28±1.24) points and (28.52±4.25) points respectively before treatment, and (13.38±7.96) points and (9.11±5.48) points respectively after treatment. The MASI scores of the two groups were decreased after treatment, which of the combined group was lower than that of the Q-switched laser group ( t=3.06, P<0.05). The total clinical effective rate of the combination group (93.75%) was higher than that of the Q-switched laser group (79.17%) (χ 2=4.36, P<0.05). The incidence rate of hyperpigmentation (2.08%) and recurrence rate (2.08%) of the combination group were lower than those of the Q-switched laser group (14.58%, 16.67%) (χ 2=6.01, P<0.05). Conclusions:Tranexamic acid radiofrequency introduction combined with Q-switched laser comprehensive treatment can improve skin lesions and clinical efficacy in patients with moderate to severe melasma, and reduce pigmentation and recurrence.

Objective : To analyze the overall survival( OS) of sequential osimertinib treatment in patients with epidermal growth factor receptor(EGFR) exon 20 T790M mutant advanced non⁃small cell lung cancer(NSCLC) and risk factors of the efficacy of sequential osimertinib treatment. Methods : The data of 138 advanced NSCLC patients with acquired EGFR exon 20 T790M mutation who took sequential osimertinib as second⁃line treatment. KaplanMeier variable was used for survival analysis. The Log⁃rank method was used for univariate analysis. The COX risk regression model was used for multivariate analysis. The survival status and influencing factors of patients treated with sequential osimertinib were analyzed. Results : At the last follow⁃up , 99 of the 138 patients died. Median progression free survival (PFS1)of first⁃line of first⁃ or second⁃generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR⁃TKIs) was 11 months (95% CI: 10. 1 - 11. 9) ; median PFS2 of osimertinib was 10 months (95% CI: 8. 5 - 11. 5) ; The median PFS with sequential osimertinib treatment was 24 months(95% CI: 21. 7 -26. 3) , the median OS was 32 months(95% CI: 28. 9 - 35. 1) . In univariate and multivariate analysis , PFS1 was an independent prognostic factor for PFS and OS(P < 0. 001) . Conclusion Sequential osimertinib treatment for advanced NSCLC patients with acquired EGFR exon 20 T790M mutation achieved good PFS(24 months) and OS (32 months) .

OBJECTIVE To excavate and evaluate β-blockers associated with acute renal failure（ARF）signal. METHODS Using the report odds ratio （ROR）method and Bayesian confidence interval progressive neural network （BCPNN）method，signal detection and analysis were performed for 4 kinds of β-blockers（metoprolol，bisoprolol，atenolol，nebivolol）associated with ARF Δ 基金项目：重庆市临床药学重点专科建设项目 （No.渝卫办发 in FDA adverse event reporting system （FAERS）from the two 〔2020〕68号）；重庆医科大学未来医学青年创新团队发展支持计划项 dimensions of Standard International Dictionary of Medical 目（No.W0081） Terms （MedDRA） analysis query （SMQ） term set and ＊药师，硕士研究生。研究方向：药物警戒。电话：023-68485161。 preferred term （PT） level terms. When the two methods E-mail：2020121624@stu.cqmu.edu.cn detected positive signals at the same time ，it indicated that # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药物警 suspicious signals were detected. RESULTS Totally 14 328 戒。电话：023-63625666。E-mail：jiayuntaomail@hospital.cqmu.edu.cn ARF reports of 4 kinds of β-blockers were retrieved within the ·1380· China Pharmacy 2022Vol. 33 No. 11 中国药房 2022年第33卷第11期 narrow sense of “acute renal failure ”in SMQ term set ，of which men （6 964）were more than women （6 206）. The age of patients was mainly concentrated in the middle-aged and elderly （≥45 years old ），and serious adverse events accounted for 77.23％. The results of signal retrieval based on SMQ term set showed that ROR values and 95％ confidence intervals of metoprolol ，bisoprolol， atenolol and nebivolol detected by ROR method were 2.58（2.51，2.65），5.30（5.14，5.47），2.80（2.69，2.91）and 3.28（3.04， 3.53）respectively. The signal components （IC）detected by BCPNN method and the lower limit of IC were 1.29（1.25），2.26 （2.22），1.42（1.36）and 1.64（1.53）respectively，suggesting suspicious signals were detected in these four kinds of β-blockers associated ARF. The results of signal detection based on PT level terms showed that 37 positive signals were detected by ROR method，38 positive signals were detected by BCPNN method ，and 36 suspicious signals were detected by the two methods at the same time. For each drug ，12 suspicious signals of metoprolol were detected at the same time ，9 suspicious signals of bisoprolol and atenolol were detected at the same time ，and 6 suspicious signals of nebivolol were detected at the same time ；the number and type of signals were different among the 4 kinds of drug. CONCLUSIONS Four kinds of β-blockers may cause ARF. Compared with metoprolol and atenolol ，bisoprolol and nebivolol have strong statistical correlation with ARF ，suggesting that medical personnel should pay attention to the possible renal related adverse reactions of these drugs in the process of clinical use.