ObjectiveThis study aims to conduct a 28-day oral toxicity test to observe the subacute toxic effects of Ganoderma lucidum spore oil in rats, elucidate its impacts on physiological indicators in rats, and provide a scientific basis for the safety evaluation of this substance. MethodsEighty 4-week-old specific pathogen-free (SPF) SD rats were randomly divided into a control group and three dose groups: low-dose (0.83 g/kg), medium-dose (1.67 g/kg), and high-dose (3.33 g/kg), with 10 males and 10 females in each group. The experimental groups were given Ganoderma lucidum spore oil by gavage at the corresponding doses, while the control group was given the same volume of edible corn oil. Administration lasted for 28 consecutive days, during which the rats had free access to food and water. The general condition of the rats was observed, and body weight, food intake, and food utilization rate were measured. After the treatment period, urine was collected from rats in each group for routine urinalysis. Blood samples were collected from the abdominal aorta under anesthesia induced by intraperitoneal administration of Zoletil 50 (5 mg/kg) and xylazine hydrochloride (10 mg/kg) for complete blood count, coagulation testing, and serum biochemical analyses. Gross necropsy was performed in all rats. Organs were excised and weighed, organ coefficients of major organs were calculated, and histopathological examinations of major organs were conducted in the control and high-dose groups. ResultsDuring the entire experimental period, all rats in the control and the three dose groups thrived without any mortality. No abnormal behaviors or clinical signs were observed in any of the groups. In the serum biochemistry, a statistically significant increase (P<0.05) in total protein was found in the high-dose female group compared with the control group. However, there was no dose-response relationship, and the values remained within the normal range of historical data in our laboratory; therefore, the increase was considered not biologically significant. Rats in the remaining groups showed no statistically significant differences (all P>0.05) in complete blood count, serum biochemical parameters, coagulation parameters, urinalysis parameters, or organ coefficients compared with the control group. Histopathological examination revealed no significant abnormalities. ConclusionThe results indicate that Ganoderma lucidum spore oil does not exhibit significant subacute toxicity in SD rats at the tested dose levels.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective:To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas.Methods:The clinical data of 61 patients who underwent colonoscopy in the People's Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group.According to the colonoscopy results,they were divided into control group(29 cases),non-adenomatous polyp group(12 cases),adenoma group(10 cases),colorectal cancer group(10 cases).17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group.Before bowel preparation for colonoscopy,the fecal samples were collected.Then the DNA of bacteria in the fecal samples was extracted.The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced.The species diversity of fecal flora was analyzed.Results:Alpha diversity analysis showed that the species diversity of samples from the high al-titude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group,and the species diversity of colorectal samples from the high al-titude colorectal cancer group was higher than that of the other two groups.While beta diversity showed no significant difference among the five groups.Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area,while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area.Differences were found in genus level analysis that the abundance of Bacteroides,Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area;the abundance of Blautia and Collinsella in the high altitude control group was the highest.Lacto-bacillus was not detected in the low altitude control group,while there was a highly significant difference(P＜0.05)in the level of Lactobacillus in the four groups of high altitude area,and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups.In the four groups of samples at high altitude,the abundance of Bifidobacterium decreased significantly,while the abundance of Christensenellaceae_R-7_group increased significantly.Conclusion:Compared with the high and low altitude controls,the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different.And the abundance of species are also diffe-rent at the phylum and genus levels,suggesting that altitude factors may have some influence on intestinal flora.

Objective:To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas.Methods:The clinical data of 61 patients who underwent colonoscopy in the People's Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group.According to the colonoscopy results,they were divided into control group(29 cases),non-adenomatous polyp group(12 cases),adenoma group(10 cases),colorectal cancer group(10 cases).17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group.Before bowel preparation for colonoscopy,the fecal samples were collected.Then the DNA of bacteria in the fecal samples was extracted.The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced.The species diversity of fecal flora was analyzed.Results:Alpha diversity analysis showed that the species diversity of samples from the high al-titude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group,and the species diversity of colorectal samples from the high al-titude colorectal cancer group was higher than that of the other two groups.While beta diversity showed no significant difference among the five groups.Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area,while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area.Differences were found in genus level analysis that the abundance of Bacteroides,Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area;the abundance of Blautia and Collinsella in the high altitude control group was the highest.Lacto-bacillus was not detected in the low altitude control group,while there was a highly significant difference(P＜0.05)in the level of Lactobacillus in the four groups of high altitude area,and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups.In the four groups of samples at high altitude,the abundance of Bifidobacterium decreased significantly,while the abundance of Christensenellaceae_R-7_group increased significantly.Conclusion:Compared with the high and low altitude controls,the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different.And the abundance of species are also diffe-rent at the phylum and genus levels,suggesting that altitude factors may have some influence on intestinal flora.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective:To analyze the relationship between hematological and genotype characteristics of fetuses and patients with hemoglobin (Hb) H disease and their natural disease progression.Methods:From 2010 to 2022, a total of 1 252 blood samples from fetuses and patients with Hb H disease who visited the Guangxi Zhuang Autonomous Regional Maternal and Child Health Hospital were collected (including 174 umbilical cord blood samples, 1 062 peripheral blood samples from patients over 2 years old, and 16 peripheral blood samples from patients with rare cases of genotype Hb H). Additionally, 278 peripheral blood samples were collected from patients aged 0 - 2 years old with Hb H 3.7, Hb H 4.2, Hb H CS, and Hb H WS disease for the study of trends in red blood cell development. Multiple probe hybridization and microarray comparative genomic hybridization technology combined with first-generation Sanger sequencing were used for rare mutation detection.Results:Among the 1 062 Hb H disease patients over 2 years old, 62.34% (662/1 062) had gene deletion (--/-α), of which Hb H 3.7 (-- SEA/-α 3.7) and Hb H 4.2 (-- SEA/-α 4.2) were the most common, accounting for 42.28% (449/1 062) and 19.11% (203/1 062) of the total, respectively. Among the non-deletion genotypes (--/αα T or α Tα/αα T), Hb H CS (-- SEA/α CS), Hb H WS (-- SEA/α WS) and α CSα/α CSα accounted for 16.85% (179/1 062), 16.48% (175/1 062) and 1.98% (21/1 062), respectively. The 81.12% (537/662) of patients with deletional Hb H disease showed mild to moderate anemia, with Hb H detection rates ranging from 75% to 80%. Among non-deletional Hb H disease, Hb H WS disease showed the mild (blood Hb concentration > 95 g/L in 90% of patients) phenotype while Hb H CS and Hb H QS (-- SEA/αα QS) patients had moderate to severe anemia, with Hb H detected in peripheral blood at higher levels than in other types of Hb H disease patients. Except for Hb H CS and Hb H QS, which did not show a significant increase in Hb A2 levels when complicated with β-thalassemia, Hb A2 levels were increased (> 3.5%) in all other types of Hb H disease patients. When Hb H disease was complicated with β-thalassemia, Hb H peaks were not detected in either type of Hb H disease. The results of red blood cell development trend detection showed that erythrocyte counts were elevated in patients with Hb H disease compared to their normal counterparts; whereas, blood Hb, mean erythrocyte volume (MCV) and mean erythrocyte hemoglobin content (MCH) were lower than in their normal counterparts ( P < 0.05) and decreased to the minimum at 6 months to 1 year of age. Patients with Hb H CS disease, as the most severe form of anemia, had the highest MCV values ( P < 0.001). The results of fetal cord blood with Hb H disease showed that α CSα/α CSα caused severe intrauterine anemia, followed by Hb H QS and Hb H CS. The content of Hb Bart's in umbilical cord blood was negatively correlated with the severity of anemia ( rs = - 0.58, P < 0.001). When Hb H disease was complicated with β-thalassemia, there was no significant improvement in fetal anemia, and the Hb Bart's content did not change significantly ( P > 0.05). In addition, Hb H 21.9 (-α 21.9kb/-- SEA) and Hb H 2.4 (-α 2.4/-- SEA) were common in patients with deletion rare Hb H. In patients with non-deletion rare Hb H, αα Amsterdam-A1/-- SEA and αα Hb G-Georgia/-- SEA were both first reported. Conclusions:There is heterogeneity in clinical manifestations of patients with different types of Hb H disease or same type of Hb H disease at different developmental stages. When patients with Hb H are complicated with β-thalassemia, the phenotype of patients with the deletion type is improved, while that of patients with the non-deletion type is not. Compared to normal individuals, patients with Hb H disease have lower blood Hb concentration, MCV and MCH, and more rapid physiological changes in red blood cells.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective: Tracking the information on 1.69 million fetal cases across Guangxi Zhuang Autonomous Region (Guangxi) so as to study the occurrences of total and major birth defects in order to evaluate the ability on related prevention and control programs in Guangxi. Methods: Using the self-developed "Gui Women’s System" to establish a database of 1.69 million fetal cases in Guangxi and to analyze the distribution of time, space and population, as well as the outcomes of pregnancy, using the big data. Results: During the 29 months of observation, the overall live birth rate was 99.25%, with stillbirth rate during pregnancy as 0.44%, stillbirth rate during birth as 0.02%, and the 0-6 days mortality rate as 0.14%. The total detection rate on birth defects was 197.63/10 000; the incidence rate was 103.04/10 000, the birth rate was 102.55/10 000. The overall discovery rate of major birth defects was 48.33/10 000, with the incidence rate as 783 000, the birth rate as 0.58/10 000. The discovery rates of major birth defects in 14 cities were between 35 and 68/10 000, and the birth rate dropped significantly to less than 1.00 in 10 000. Nationalities showed that the number of pregnant women with birth defects more than 50 000 would include Hui (9.68/10 000), Yao (9.57/10 000), and Jing (9.37/10 000). With the increasing age of gestation, number of birth defects, incidence of major birth defects also increased. Ninety-five percent of the major birth defects were found within <28 weeks and with the top 5 kinds of major birth defects as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). The top 5 major birth defects appeared as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). Conclusion Programs leading to increase the rate on discovery of major birth defects were fundamental in effectively reducing the major birth defects.

Objective To investigate the preventive effects of Gushudan on osteoporosis in rats after administrated prednisolone.Methods Wistar male rats(60) were divided into six groups: control group,model group,Gushudan groups(3,1,and 0.3 g/kg),and Gushukang 1 g/kg group.The effect was observed by measuring the levels of blood calcium,blood phosphorus,blood BGP content,bone calcium,bone phosphorus,bone density,and hone biomechanics.Results After eight weeks,Gushudan significantly increased the bone density,bone biomechanics,blood BGP content,bone calcium,and bone phosphorus in model group rats.Conclusion Gushudan could increase bone density,bone biomechanics,blood BGP content,bone calcium,and bone phosphorus induced by prednisolone.These results suggest that Gushudan has a distinct preventive effect on osteoporosis rats.