OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

Objective To analyze the antibody types of autoimmune hemolytic anemia(AIHA)patients in Panyu dis-trict,Guangzhou and track the therapeutic effect of blood transfusion,so as to provide reference for clinical transfusion treat-ment strategy of AIHA patients.Methods From January 2021 to October 2023,96 ambiguous cross-matching blood sam-ples from Blood Transfusion Departments of local hospitals sent to Panyu Central Blood Station were analyzed,and 25 sam-ples of AIHA patients were identified.Then blood group identification,Rh system antigen phenotyping,antibody screening and cross-matching were further performed to analyze the correlation between antibody types and transfusion efficacy in AIHA patients.Results Among the 25 samples of AIHA patients,17 showed consistency between forward and reverse blood grouping and8 showed discrepancy.There were 19(19/25,76%)samples incompatible in cross match on the major side,of which 18(18/19,94.7%)were positive for direct Coombs test,autoantibodies and non-specific antibodies,and1(1/19,5.3%)was positive for autoantibody and alloantibody.There were 6(6/25,24%)samples compatible in cross match on the major side,of which 3(3/6,50%)were positive for autoantibodies,3(3/6,50%)were positive for au-toantibody and alloantibody.Of the 25 AIHA patients,20 received blood transfusion treatment and could be traced,and 5 patients did not receive blood transfusion treatment or transferred to other hospitals and could not be traced.Blood transfu-sion was effective in 11(11/20,55%)cases,partially effective in 6(6/20,30%)cases,and ineffective in 3(3/20,15%)cases.Among the ABO blood group incompatibility samples,transfusion was effective or partially effective in 17(17/20,85%)cases.Conclusion The transfusion efficacy of AIHA patients is not directly related to the results of cross-matc-hing.Under the premise of regulating the autoimmune environment and eliminating the ABO blood group incompatibility caused by unexpected alloantibodies,AIHA patients with incompatible cross-matching can be transfused when necessary,and transfusion of ABO and Rh system antigen homologous blood can improve the safety and efficiency of transfusion.

Objective:To evaluate the effects of inhaling high concentration hydrogen on myocardial injury and mitochondrial biogenesis in septic mice.Methods:One hundred and twenty-eight clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis group (group Sep), and sepsis+ hydrogen group (group Sep+ H). The sepsis model was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and Sep+ H groups, 67% H 2 was inhaled for 1 h starting from 1 and 6 h after operation, respectively. Twenty mice in each group were randomly selected to observe the survival conditions at 7 days after operation. Blood samples were taken from the remaining mice at 24 h after operation for determination of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) (by enzyme-linked immunosorbent assay), for examination of the pathological changes of myocardial tissues (by HE staining), and for determination of the mitochondrial membrane potential (MMP) (by fluorescence spectrophotometry), ATP content (by luciferase assay), and expression of myocardial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM) (by Western blot). Results:Compared with Sham group, the survival rate was significantly decreased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were increased, the MMP and content of ATP in myocardial mitochondria were decreased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was down-regulated in Sep group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with group Sep, the survival rate was significantly increased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were decreased, the MMP and content of ATP in myocardial mitochondria were increased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was up-regulated in group Sep+ H ( P<0.05). Conclusions:Inhaling high concentration hydrogen can attenuate sepsis-induced myocardial injury in mice, and the mechanism may be related to promotion of mitochondrial biosynthesis and improvement in mitochondrial function.

Objective:To evaluate the effects of inhalation of high-concentration hydrogen on acute kidney injury (AKI) and mitochondrial dynamics in septic mice.Methods:One hundred and twenty-eight male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis AKI group, and sepsis AKI+ hydrogen group (group S-AKI+ H). A mouse model of sepsis-induced AKI was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and S-AKI+ H groups, 67% H 2+ 33% O 2 was inhaled for 1 h starting from 1 and 6 h after sham operation or developing the model, respectively. Twenty mice were selected to observe the survival at 7 days after developing the model. At 24 h after developing the model, blood samples were collected for determination of serum BUN and Cr concentrations (by colorimetric analysis), and renal tissues were obtained for determination of the contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and high mobility group protein B1 (HMGB1) (by enzyme-linked immunosorbent assay), activities of superoxide dismutase (SOD) and catalase (CAT) (by spectrophotometry) and expression of dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2) (by Western blot). The damage to the renal tubules was scored after HE staining. Results:Compared with Sham group, the survival rate was significantly decreased, the serum BUN and Cr concentrations, renal tubular damage score and contents of TNF-α, IL-1β and HMGB1 were increased, the activities of SOD and CAT were decreased, the expression of Drp1 was up-regulated, and the expression of Mfn2 was down-regulated in S-AKI group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with S-AKI group, the survival rate was significantly increased, the serum BUN and Cr concentrations, renal tubular injury score and contents of TNF-α, IL-1β and HMGB1 were decreased, the activities of SOD and CAT were increased, the expression of Drp1 was down-regulated, and the expression of Mfn2 was up-regulated in S-AKI+ H group ( P<0.05). Conclusions:Inhalation of high-concentration hydrogen can alleviate AKI in septic mice, and the mechanism may be related to inhibition of renal mitochondrial fission and promotion of mitochondrial fusion.

Objective:To explore the effect of Xingnao Kaiqiao acupuncture treatment on brain network reorganization for the patients with stroke recovery, and therefore understand the neural mechanism underlying Xingnao Kaiqiao acupuncture treatment.Methods:Prospective case series study. Thirteen acute ischemia stroke patients were recruited from the Department of Neurology, Shanghai Minhang Hospital of Integrated Traditional Chinese and Western Medicine from Aug 2018 to Oct 2019. They were treated with Xingnao Kaiqiao acupuncture once a day for 10 consecutive days in addition to routine treatments, and received clinical assessments before treatment and 14 days after treatment onset. EEG signals were recorded during the first acupuncture treatment, from before inserting the needles (the baseline), during needle retention, to after removal of the needles. The brain network was constructed using phase locking index, and its clustering coefficient (CC), characteristic path length (PL) and small-worldness (S) were analyzed using one-way repeated ANOVA.Results:Compared with the baseline, the CC of delta-band network (sparsity=0.10: t=3.306, P=0.006; 0.12: t=2.909, P=0.013; 0.14: t=2.331, P=0.038) and the PL of delta-band (sparsity=0.12: t=3.236, P=0.007; 0.14: t=2.754, P=0.017, 0.18: t=2.878, P=0.014) and alpha-band (sparsity=0.10: t=2.432, P=0.032) networks were significantly decreased during the needle retention stage. Clinical assessments demonstrated a significant treatment efficacy of Xingnao Kaiqiao acupuncture, and its efficacy which was indicated by improved NIHSS score, was significantly correlated with the CC changes in the delta band network from baseline to needle retention. The correlation was strongest when the network sparsity was 0.12 ( r=0.78, P=0.002). Conclusion:Xingnao Kaiqiao acupuncture can regulate the brain network of stroke patients in real time, and this immediate regulation maybe associated with its treatment effect.

Objective: To understand the epidemiological characteristics of school foodborne disease outbreaks in Liaoning Province, and to provide scientific basis for effective prevention and control of school foodborne disease outbreaks in the future. Methods: An epidemiological study was conducted on the school foodborne disease outbreaks reported by the National Foodborne Disease Outbreak Surveillance System in Liaoning Province from 2011 to 2021. The influencing factors of school foodborne disease outbreaks were analyzed by binary Logistic regression. Results: From 2011 to 2021, a total of 29 school foodborne outbreaks were reported in Liaoning Province, with accumulative cases of 1 003, 218 hospitalized cases and no death cases. The number of outbreaks and cases were the highest in 2020(7 cases, 320).The incidence of the disease showed a bimodal distribution throughout the year, with the peak in March and December, and the number of outbreaks in schools in March was the largest(8 cases,27.59%). Primary and secondary schools reported the largest number of incidents, cases and hospitalizations(12 cases, 555, 97). The mean interval of outbreak reporting was longest in junior college (32.01 h), while the mean duration of outbreak was longest in university ( 52.33 h ). Most of cases (536,53.44%) had vomiting symptoms. Staphylococcus aureus toxin, Bacillus cereus toxin and Norovirus caused more incidents(3 cases for each one). In addition to the unknown causes, improper processing and cross contamination were the main causes(6 cases for each one). Headache index was positively correlated with outbreak size in schools ( OR = 9.78). Clinical symptoms fever and exposure duration event indexes were positively correlated with the reporting time interval of school outbreak events ( OR =7.08, 22.40)( P <0.05). Conclusion It is necessary to strengthen the management and supervision of school catering institutions in winter and spring, optimize the reporting process, and effectively reduce the scale of outbreaks of foodborne diseases in schools.

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P < 0.001). There were significant differences in the number of patients with low or high expression of miR-486-5p between the patients with different TNM stages, presence or absence of lymphatic metastasis, and presence or absence of distant metastasis ( χ 2 =13.765, 5.157, and 6.638, all P < 0.05). Compared with CA19-9 alone, miR-486-5p+CA19-9 had a significantly better value in distinguishing the operable group from the benign pancreatic disease group (area under the ROC curve [AUC]=0.87, 95% confidence interval [ CI ]: 0.760-0.942; with a sensitivity of 81.3% and a specificity of 83.3%), distinguishing the operable group from the healthy control group (AUC=0.92, 95% CI : 0.836-0.970; with a sensitivity of 90.6% and a specificity of 86.4%), and distinguishing the operable group from the non-operable group (AUC=0.94, 95% CI : 0.884-0.998; with a sensitivity of 85.7% and a specificity of 93.7%) ( Z =2.841, 2.510, and 2.387, all P < 0.05), and the optimal cut-off values were 3.12, 3.21, and 6.63, respectively. Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.

Objective:To detect the known hotspot mutations of GNAS in children with McCune-Albrigtht syndrome(MAS) by droplet digital PCR, and to explore its application value in the diagnosis of MAS.Methods:A total of 122 children with MAS were enrolled in the pediatric department of Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University. For the known mutation hotspot of GNAS gene (R201H/C), dd-PCR, real-time fluorescent pyrophosphatic activation polymerase reaction (PAP) and second-generation sequencing were used to detect the presence of gene mutation and to analyse the relevance with the clinical features.Results:GNAS gene mutation was detected in 89 out of 122 children with MAS and 57 cases were found to have mutations. The positive rates of ddPCR, PAP, and second generation sequencing were 77.42%, 29.03%, and 56.25%, respectively. The GNAS gene mutation was detected in all classical triad patients. Among them, the positive rates of ddPCR in peripheral blood of typical and atypical children were 100% and 73.1% respectively, which were significantly higher than those of the other two methods. The detection rate of GNAS mutation in precocious puberty with bone lesions was higher than that in precocious puberty with skin lesions, suggesting that fibrous dysplasia with precocious puberty is an important basis for clinical diagnosis of MAS in children.Conclusion:Precocious puberty is the most common endocrine manifestation of MAS in children. Bone fibrous dysplasia with precocious puberty is an important factor in clinical diagnosis. ddPCR has high sensitivity, which can be helpful for molecular diagnosis of MAS.

Objective:To evaluate the reliability of flow cytometry (FCM) for diagnosing lymphoma associated hemophagocytic syndrome (LAHS).Method:The clinical data in 57 patients with hemophagocytic lymphohistiocytosis (HLH)were retrospective analyzed at Peking University Shenzhen Hospital from July 2010 to July 2019. All patients were performed bone marrow FCM and bone marrow pathological examination before final diagnoses were made. The golden diagnosis criterion was based on clinical, biochemical and histopathological evidence, which was regarded as the standard to evaluate the sensitivity and specificity of FCM analysis in diagnosing LAHS.Results:Among 57 cases, 36 cases were eventually diagnosed with LAHS, including 15 B-cell lymphoma(14 diffuse large B-cell lymphoma, 1 B-cell lymphoma with reactive T-cell hyperplasia), 13 aggressive NK/T cell lymphoma/leukemia, 2 cases of gamma-delta T-cell lymphoma, 4 angioimmunoblastic T-cell lymphoma, 1 enteropathy-associated peripheral T-cell lymphoma and 1 anaplastic T-cell lymphoma. Lymphoma cells in bone marrow were detected in all patients by FCM except one ENTCL patient. The sensitivity and the specificity of FCM in LASH compared to bone marrow biopsy were 97.2%( P=0.014)and 90.5%( P=0.488) respectively. In the other 21 non-LAHS patients, T cell receptor Vβ (TCRVβ) rearrangement was detected in 2 patients with Epstein-Barr virus (EBV) associated primary HLH. Conclusions:FCM effectively detects lymphoma cells in bone marrow of lymphoma patients with LHL, suggesting that FCM could be an important indicator for the diagnosis of LAHS. FCM also has the advantage in differentiating LAHS from other HLH.

OBJECTIVE: To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty. METHODS: Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2 mg·m ·d for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume. RESULTS: After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 ( < 0.01); the predicted adult height (PAH) increased from (156.2±5.9)cm to (158.4±2.1)cm after treatment ( < 0.05); the vaginal bleeding was reduced and the estradiol level decreased, while the teststosterone level and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion and abnormal liver function were observed. CONCLUSIONS Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.
Aromatase Inhibitors ; Child ; China ; Female ; Fibrous Dysplasia, Polyostotic ; Humans ; Letrozole ; Puberty, Precocious