Objective:To analyze the epidemiological characteristics and delay in detection of reported brucellosis cases in Nangang District of Harbin City, Heilongjiang Province, in order to provide a basis for improving targeted measures for brucellosis prevention and control.Methods:Data on brucellosis reported in Nangang District of Harbin City between 2018 and 2022 were obtained from the China Disease Prevention and Control Information System. A descriptive analysis was conducted to outline the epidemiological status, epidemiological features, and sources of cases. Seasonal patterns of brucellosis were assessed using the concentration degree and seasonal index methods. Joinpoint regression model was used to analyze the trend of delay in detection.Results:From 2018 to 2022, a total of 4 428 cases of brucellosis were reported in Nangang District, with 1 183 cases (26.72%) reported in 2018 and 528 cases (11.92%) reported in 2022. The gender ratio of the cases was 2.80 ∶ 1.00 (3 264 ∶ 1 164). Most cases occurred in individuals aged 30 to 59 years (73.19%, 3 241/4 428). Occupationally, farmers comprised the majority of cases (88.73%, 3 929/4 428), followed by homemakers/unemployed individuals (3.73%, 165/4 428), and students (2.03%, 90/4 428). Regarding case origin, 31.48% (1 394/4 428) were from Harbin City, while 64.97% (2 877/4 428) originated from other cities within Heilongjiang Province, predominantly from Suihua City (38.89%, 1 722/4 428). Additionally, 157 cases (3.55%, 157/4 428) were reported from outside Heilongjiang Province, all of which were from Inner Mongolia Autonomous Region and Jilin Province. Brucellosis incidence showed weak seasonality ( M = 0.230), with the epidemic period spanning from March to August. During this period, seasonal indices C exceeded 100%, peaking in July (168.02%). From 2018 to 2022, the average annual delay rate in case detection was 20.14% (892/4 428). The delayed detection rates of brucellosis cases in each year were 30.68% (363/1 183), 17.86% (200/1 120), 17.23% (117/679), 12.75% (117/918), and 17.99% (95/528), respectively (average annual percentage change = - 17.52%, P = 0.090). Conclusions:Brucellosis in Nangang District of Harbin Citydemonstrates weak seasonality, with peak incidence occurring from March to August. Detection delays remain a concern, highlighting the need for sustained surveillance and the implementation of integrated, multi-sectoral prevention and control measures.

Objective:To investigate the efficacy and safety of Doxycycline in the treatment of Mycoplasma pneumoniae pneumonia (MPP). Methods:Case series study.A retrospective observational study was conducted on 202 patients diagnosed with MPP in Beijing United Family Hospital from January 2022 to January 2024.The patients were divided into 3 groups according to antibiotics used: Azithromycin group which enrolled 93 cases, 60 cases (Azithromycin alone group) were included after excluding 33 cases with adding steroids; Doxycycline group which enrolled 32 case, 31 cases (Doxycycline alone group) were included after excluding 1 case with adding steroids; Azithromycin switch to Doxycycline when diagnosed Macrolides-unresponsive MPP(MUMPP). Azithromycin switch to Doxycycline group which enrolled 77 cases, 73 cases (switch group) were included after excluding 4 cases with adding steroids.Results used the Mann-Whitney U test, Chi-square test or exact test analyse, comparing the differences in defervescene time, hospitalization day, outcomes and side effects in each group. Results:The fever duration in the Doxycycline alone group was 48(36, 48) h, which was significantly shorter than that in the Azithromycin alone group[120(120, 144) h] ( Z=-7.646, P<0.001). The hospitalization time in the Doxycycline alone group was [3(3, 4) d], which was significantly shorter than that in the Azithromycin alone group [4(3, 5) d] ( Z=-3.368, P=0.002). The medium fever duration in the switch group after Azithromycin was changed to Doxycycline was 48 h, which was not statistically significantly different from that in the Doxycycline alone group ( Z=-0.571, P=0.849). The medium hospitalization time in the switch group after Azithromycin changed to Doxycycline was 4 d, which was significantly longer than that in the Doxycycline alone group (3 d) ( Z=-2.759, P=0.008). Among 93 cases enrolled in the Azithromycin group, 33 cases (35.5%) converted to unresponsive MPP(UMPP), 23 cases (24.7%) progressed to refractory MPP (RMPP), and 33 cases (35.5%) added steroids.Among 32 cases included in the Doxycycline group, 1 case (3.1%) converted to UMPP, no case developed to RMPP, and 1 case (3.1%) added steroids.The above-mentioned 3 proportions were significantly different between the two groups (all P<0.001). Among 93 cases enrolled in the Azithromycin group, 11 cases (11.8%) progressed to severe MPP (SMPP), and 13 cases (14.0%) developed complications.In 32 cases included in the Doxycycline group, 1 case (3.1%) progressed to SMPP, and 3 cases (9.4%) developed complications.The difference in these 2 proportions was not statistically significant between the two groups ( P=0.294, 0.760). In 77 patients included in the Azithromycin switch to Doxycycline group, there were 4 cases converting to UMPP, 4 cases converting to RMPP and 4 cases adding steroids, which were not statistically significantly different from those in the Doxycycline group (all P=0.540). In the Azithromycin switch to Doxycycline group, there were 3 cases progressing to SMPP, and 7 cases developed complications, which were not statistically significantly different from those in the Doxycycline group (all P=1.000). Conclusions:Doxycycline can improve the fever symptom, shorten illness duration and hospitalization time, and reduce steroid usage and the proportions of UMPP and RMPP in pediatric MPP.Switching to Doxycycline is recommended for MUMPP patients as Doxycycline is effective for the treatment of pediatric MPP and no tetracycline pigmentation teeth now.

Objective:To characterize the minimal inhibitory concentration (MIC) of macrolides against clinical Mycoplasma pneumoniae (MP) isolates and to investigate the significance of 23S rRNA mutations. Methods:Cross-sectional study.A total of 288 clinical MP strains preserved in the laboratory from 2016 to 2021 were taken for macrolide resistance gene testing and the evaluation of in vitro susceptibility to Azithromycin and Erythromycin.MIC 50 and MIC 90 values were calculated separately for macrolide-susceptible and -resistant strains. Results:All 288 MP strains underwent the test of in vitro susceptibility to Azithromycin, while 86 of them were additionally tested for Erythromycin.Among these strains, 22 strains were Azithromycin-sensitive, and 266 strains were Azithromycin-resistant.A2063G mutations were detected in 260 (97.7%) strains, while A2064G mutations were detected in 6 (2.3%) strains.Azithromycin-resistant strains had an MIC 50 of 128.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 16.000 and 512.000 μg/mL.Seven strains were sensitive and 79 strains were resistant to Erythromycin.Among Erythromycin-resistant strains, A2063G mutations were detected in 73 (92.4%) strains, while A2064G mutations were detected in 6 (7.6%) strains.Erythromycin-resistant strains had an MIC 50 of 256.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 64.000 and 1 024.000 μg/mL. Conclusions:A2063G and A2064G mutations in the 23S rRNA gene of MP are associated with high-level in vitro resistance to Azithromycin and Erythromycin, significantly limiting the clinical effectiveness of these antibiotics.Early resistance gene testing is recommended for suspected MP patients, which can help optimize the treatment, improve prognosis, and prevent resistance spread.

Objective:To analyze the epidemiological characteristics and delay in detection of reported brucellosis cases in Nangang District of Harbin City, Heilongjiang Province, in order to provide a basis for improving targeted measures for brucellosis prevention and control.Methods:Data on brucellosis reported in Nangang District of Harbin City between 2018 and 2022 were obtained from the China Disease Prevention and Control Information System. A descriptive analysis was conducted to outline the epidemiological status, epidemiological features, and sources of cases. Seasonal patterns of brucellosis were assessed using the concentration degree and seasonal index methods. Joinpoint regression model was used to analyze the trend of delay in detection.Results:From 2018 to 2022, a total of 4 428 cases of brucellosis were reported in Nangang District, with 1 183 cases (26.72%) reported in 2018 and 528 cases (11.92%) reported in 2022. The gender ratio of the cases was 2.80 ∶ 1.00 (3 264 ∶ 1 164). Most cases occurred in individuals aged 30 to 59 years (73.19%, 3 241/4 428). Occupationally, farmers comprised the majority of cases (88.73%, 3 929/4 428), followed by homemakers/unemployed individuals (3.73%, 165/4 428), and students (2.03%, 90/4 428). Regarding case origin, 31.48% (1 394/4 428) were from Harbin City, while 64.97% (2 877/4 428) originated from other cities within Heilongjiang Province, predominantly from Suihua City (38.89%, 1 722/4 428). Additionally, 157 cases (3.55%, 157/4 428) were reported from outside Heilongjiang Province, all of which were from Inner Mongolia Autonomous Region and Jilin Province. Brucellosis incidence showed weak seasonality ( M = 0.230), with the epidemic period spanning from March to August. During this period, seasonal indices C exceeded 100%, peaking in July (168.02%). From 2018 to 2022, the average annual delay rate in case detection was 20.14% (892/4 428). The delayed detection rates of brucellosis cases in each year were 30.68% (363/1 183), 17.86% (200/1 120), 17.23% (117/679), 12.75% (117/918), and 17.99% (95/528), respectively (average annual percentage change = - 17.52%, P = 0.090). Conclusions:Brucellosis in Nangang District of Harbin Citydemonstrates weak seasonality, with peak incidence occurring from March to August. Detection delays remain a concern, highlighting the need for sustained surveillance and the implementation of integrated, multi-sectoral prevention and control measures.

Objective:To investigate the efficacy and safety of Doxycycline in the treatment of Mycoplasma pneumoniae pneumonia (MPP). Methods:Case series study.A retrospective observational study was conducted on 202 patients diagnosed with MPP in Beijing United Family Hospital from January 2022 to January 2024.The patients were divided into 3 groups according to antibiotics used: Azithromycin group which enrolled 93 cases, 60 cases (Azithromycin alone group) were included after excluding 33 cases with adding steroids; Doxycycline group which enrolled 32 case, 31 cases (Doxycycline alone group) were included after excluding 1 case with adding steroids; Azithromycin switch to Doxycycline when diagnosed Macrolides-unresponsive MPP(MUMPP). Azithromycin switch to Doxycycline group which enrolled 77 cases, 73 cases (switch group) were included after excluding 4 cases with adding steroids.Results used the Mann-Whitney U test, Chi-square test or exact test analyse, comparing the differences in defervescene time, hospitalization day, outcomes and side effects in each group. Results:The fever duration in the Doxycycline alone group was 48(36, 48) h, which was significantly shorter than that in the Azithromycin alone group[120(120, 144) h] ( Z=-7.646, P<0.001). The hospitalization time in the Doxycycline alone group was [3(3, 4) d], which was significantly shorter than that in the Azithromycin alone group [4(3, 5) d] ( Z=-3.368, P=0.002). The medium fever duration in the switch group after Azithromycin was changed to Doxycycline was 48 h, which was not statistically significantly different from that in the Doxycycline alone group ( Z=-0.571, P=0.849). The medium hospitalization time in the switch group after Azithromycin changed to Doxycycline was 4 d, which was significantly longer than that in the Doxycycline alone group (3 d) ( Z=-2.759, P=0.008). Among 93 cases enrolled in the Azithromycin group, 33 cases (35.5%) converted to unresponsive MPP(UMPP), 23 cases (24.7%) progressed to refractory MPP (RMPP), and 33 cases (35.5%) added steroids.Among 32 cases included in the Doxycycline group, 1 case (3.1%) converted to UMPP, no case developed to RMPP, and 1 case (3.1%) added steroids.The above-mentioned 3 proportions were significantly different between the two groups (all P<0.001). Among 93 cases enrolled in the Azithromycin group, 11 cases (11.8%) progressed to severe MPP (SMPP), and 13 cases (14.0%) developed complications.In 32 cases included in the Doxycycline group, 1 case (3.1%) progressed to SMPP, and 3 cases (9.4%) developed complications.The difference in these 2 proportions was not statistically significant between the two groups ( P=0.294, 0.760). In 77 patients included in the Azithromycin switch to Doxycycline group, there were 4 cases converting to UMPP, 4 cases converting to RMPP and 4 cases adding steroids, which were not statistically significantly different from those in the Doxycycline group (all P=0.540). In the Azithromycin switch to Doxycycline group, there were 3 cases progressing to SMPP, and 7 cases developed complications, which were not statistically significantly different from those in the Doxycycline group (all P=1.000). Conclusions:Doxycycline can improve the fever symptom, shorten illness duration and hospitalization time, and reduce steroid usage and the proportions of UMPP and RMPP in pediatric MPP.Switching to Doxycycline is recommended for MUMPP patients as Doxycycline is effective for the treatment of pediatric MPP and no tetracycline pigmentation teeth now.

Objective:To characterize the minimal inhibitory concentration (MIC) of macrolides against clinical Mycoplasma pneumoniae (MP) isolates and to investigate the significance of 23S rRNA mutations. Methods:Cross-sectional study.A total of 288 clinical MP strains preserved in the laboratory from 2016 to 2021 were taken for macrolide resistance gene testing and the evaluation of in vitro susceptibility to Azithromycin and Erythromycin.MIC 50 and MIC 90 values were calculated separately for macrolide-susceptible and -resistant strains. Results:All 288 MP strains underwent the test of in vitro susceptibility to Azithromycin, while 86 of them were additionally tested for Erythromycin.Among these strains, 22 strains were Azithromycin-sensitive, and 266 strains were Azithromycin-resistant.A2063G mutations were detected in 260 (97.7%) strains, while A2064G mutations were detected in 6 (2.3%) strains.Azithromycin-resistant strains had an MIC 50 of 128.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 16.000 and 512.000 μg/mL.Seven strains were sensitive and 79 strains were resistant to Erythromycin.Among Erythromycin-resistant strains, A2063G mutations were detected in 73 (92.4%) strains, while A2064G mutations were detected in 6 (7.6%) strains.Erythromycin-resistant strains had an MIC 50 of 256.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 64.000 and 1 024.000 μg/mL. Conclusions:A2063G and A2064G mutations in the 23S rRNA gene of MP are associated with high-level in vitro resistance to Azithromycin and Erythromycin, significantly limiting the clinical effectiveness of these antibiotics.Early resistance gene testing is recommended for suspected MP patients, which can help optimize the treatment, improve prognosis, and prevent resistance spread.

Objective To investigate the relationship between the levels of CD4+/CD8+and D-dimer(D-D)in peripheral blood and the outcome of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods Ninety patients with EBV-HLH who were treated in Beijing Friendship Hospital from September 2021 to August 2023 were included as observation group,and additional 90 patients with infectious mononucleosis(IM)treated in the hospital contemporarily were selected as the control group.The levels of CD4+/CD8+and D-D in peripheral blood were compared between the two groups of patients to examine the correlation between the levels of CD4+/CD8+and D-D in peripheral blood and EBV-DNA load in patients with EBV-HLH,compare the outcome of patients within 3 months in terms of the levels of CD4+/CD8+and D-D in peripheral blood,evaluate the effects of CD4+/CD8+and D-D levels in peripheral blood on the risk of death from EBV-HLH,and analyze the interaction between the levels of CD4+/CD8+and D-D in peripheral blood.Results The patients in observation group showed significantly lower peripheral blood CD4+/CD8+ratio and significantly higher D-D than the patients in control group(P＜0.05).The peripheral blood CD4+/CD8+ratio was negatively correlated with EBV-DNA load(P＜0.05),and D-D was positively correlated with EBV-DNA load(P＜0.05)in EBV-HLH patients.The patients with high peripheral blood CD4+/CD8+ratio were assocaited with lower 3-month mortality rate compared to the patients with low CD4+/CD8+ratio.The patients with high D-D level were associated with higher 3-month mortality rate compared to the patients with low D-D level(P＜0.05).In EBV-HLH patients with low levels of peripheral blood CD4+/CD8+,the risk of death was 6.125 times that of the patients with high levels of CD4+/CD8+.High level D-D was associated with 14.348 times risk of death compared to the patients with low level D-D.CD4+/CD8+and D-D had synergistic effect on death of EBV-HLH patients.Conclusions Peripheral blood CD4+/CD8+levels decreased and D-D levels increased in EBV-HLH patients.Peripheral blood CD4+/CD8+levels and D-D levels and their changes may be useful for predicting the outcome of patients.

Objective:To investigate the optimal serum antibody titer in acute stage for the diagnosis of Mycoplasma pneumoniae (MP) infection by passive agglutination, and to evaluate the clinical diagnostic value of different antibody titers.Methods:A cross-sectional study.Eighty-eight pairs of clinical serum samples were collected from children with MP infection treated at the Department of Pediatrics in Shengjing Hospital of China Medical University from December 2016 to February 2017 and Children′s Hospital of Baotou in November 2019.The four-fold change of the double serum specific antibody titer was used as the gold standard, and the receiver operating characteristic (ROC) curve was plotted.When detecting the single serum in acute stage, different antibody titers were used as positive criteria to evaluate their clinical application value in the diagnosis of MP infection and find the most appropriate serum antibody titer as the diagnostic cut-off value.Results:(1)When the serum specific antibody titer ≥1∶40 was used as the positive criterion, the sensitivity was 72.9%, the area under the ROC curve was 0.817, and the specificity was 87.5%, which might cause overdiagnosis.When the serum specific antibody titer ≥1∶160 was used as the positive criterion, the specificity was 97.5%, the area under the ROC curve was 0.775, and the sensitivity was 52.1%, which might cause missed diagnosis.When the serum specific antibody titer ≥1∶80 was used as the positive criterion, the sensitivity was 60.4%, the specificity was 97.5%, and the area under the ROC curve was 0.823, overall performing better compared with the said two criteria.(2)After the disease lasted at least 5 days, blood samples were collected.About 72.5% of the children had antibodies, and 60.0% of the children had antibody titers ≥1∶80.Conclusions:(1)When the passive agglutination method is used to detect MP infection, antibody titer ≥1∶80 is recommended as the diagnostic standard.However, in clinical practice, the diagnosis of MP infection depends on clinical and other laboratory test results.(2) It is appropriate to collect blood samples on 5-7 days of illness.If MP infection is clinically suspected, and an antibody titer of 1∶40 is also suggestive, it can perform cooperative diagnosis based on molecular biology lab results or retest at a shorter interval.

Objective:To investigate drug resistance gene in Mycoplasma pneumoniae(MP) and the distribution of 13 respiratory pathogens in bronchoalveolar lavage fluid(BALF) of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:A total of 100 BALF of children with MPP in Peking University Third Hospital and Peking University First Hospital from January 2018 to January 2019 were collected.Fluorogenic quantitative PCR was used to detect nucleic acid and it′s drug resistance gene of MP and multiple PCR method was adopted to detect influenza A virus, influenza A virus-H 1N 1, influenza A virus-H 3N 2, influenza B, human parainfluenza virus, adenovirus, human bocavirus, human rhinovirus, Chlamydia pneumoniae, human metapneumovirus, MP, human coronavirus, and respi-ratory syncytial virus gene, and the results were compared by using Chi square test. Results:In 100 BALF samples, MP and drug resistance gene were detected by fluorogenic quantitative PCR.Totally, 83 cases (83.00%) were MP positive and 78 cases (93.98%) were drug resistant.All of them had the point mutations A2063G in V region of 23S rRNA domain.A total of 13 kinds of respiratory pathogens were detected by multiplex PCR method, and 89 cases (89.00%) were positive.Totally, 79 cases (79.00%) were MP positive, of which 74 cases (74.00%) detected only MP, and 5 cases (5.00%) detected MP combined with other pathogens.Other pathogens were detected in 10 cases (10.00%). The virus detection rate of 0-4 years old group was higher than that of >4-6 years old group ( P=0.042) and >6 years old group ( P=0.002), and the differences were statistically significant. Conclusions:MP can be detected in most BALF samples of MPP children, the drug resistance phenomenon is serious, and the main point mutation is A2063G.There were other respiratory pathogens and 2 or 3 pathogens were detected in a small number of BALF samples.

Objective:To investigate the common bacteria in the oropharynx of children with Mycoplasma pneumoniae pneumonia (MPP) and its clinical significance.Methods:A total of 134 children with MPP who were hospitalized in the Department of Pediatric Respiratory, Shengjing Hospital of China Medical University from December 2016 to June 2017 were selected as the research subjects, and 42 healthy children in the same hospital were selected retrospectively as the healthy control group during the same period.Fluorescent quantitative polymerase chain reaction Taqman probe was used to detect common oropharyngeal bacteria[ Streptococcus pneumoniae(SP), Moraxella catarrhalis(CTA), Haemophilus influenza(HI)] for the enrolled children.Firstly, the bacterial detection rate of MPP children and healthy children was compared.Then, according to age(<1 years old, 1-<3 years old, 3-<6 years old and 6-14 years old), bacterial detection[Mycoplasma pneumoniae(MP), MP+ bacteria]and bacterial species(MP+ SP, MP+ CTA, MP+ HI), 134 children with MPP were divided into groups to compare.Moreover, the relevant clinical datas were retrospectively analyzed by rank sum test and chi- square test. Results:Among 134 children with MPP, 79 (58.96%) children were detected bacteria, and 17 (40.48%) children were detected bacteria among 42 healthy children, with statistically significant differences( χ2=4.404, P<0.05). Compared with the MP group, the level of white blood cell (WBC)[8.5(6.7, 12.0)×10 9/L vs.7.8(5.8, 9.3)×10 9/L, Z=-2.232], C reactive protein(CRP)[19.2(7.2, 35.0) mg/L vs.8.4(3.4, 24.6) mg/L, Z=-2.810], lactate dehydrogenase(LDH)[286(244, 365) U/L vs.250(210, 302) U/L, Z=-2.474] and the incidence of lobar pneumonia[40.51%(32/79 cases) vs.18.18%(10/55 cases), χ2=7.510], pleural effusion[13.92%(11/79 cases) vs.3.64%(2/55 cases), χ2=3.917], refractory Mycoplasma pneumoniae pneumonia (RMPP)[34.18%(27/79 cases) vs.18.18%(10/55 cases), χ2=4.151] in MP+ bacteria group were higher; the course of fever[10(7, 12) d vs.8(6, 10) d, Z=-2.706] and duration of antibiotic use[16(13, 19) d vs.12(9, 16) d, Z=-3.747] in MP+ bacteria group were longer (all P<0.05). The level of WBC in MP+ SP group[12.20(7.80, 17.30)×10 9/L] was higher than that in MP+ HI group [6.75(5.37, 9.44)×10 9/L], and the differences were statistically significant( Z=11.574, P<0.05), and the incidence of lobar pneumonia in MP+ SP group [56.67%(17/30 cases)]was higher than that in MP+ CTA group [0(0/3 cases)]and MP+ HI group[18.75%(3/16 cases)], and the differences were statistically significant( χ2=9.770, P<0.05). Conclusions:Bacterial colonization or infection is more likely to occur in the oropharynx of children with MPP.When WBC, CRP, and LDH are significantly increased and the image shows a large consolidation or pleural effusion, it may indicate mixed bacterial infection, longer course of fever and higher incidence of RMPP, and the common mixed bacteria is SP.