BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. RESULTS: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. CONCLUSION Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.
Child ; Female ; Humans ; Male ; Azacitidine/therapeutic use* ; Cladribine/therapeutic use* ; Retrospective Studies ; Leukemia, Myeloid, Acute/genetics* ; Neutropenia ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

To investigate the effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism, we used Huh7, Huh7.5, H460, and C3A cell lines as in vitro models to evaluate the cytotoxicity and antiviral activity of FFYH by observation of cell pathogenic effect (CPE); and then the inhibitory effect of FFYH on the transcription expression of coronavirus RNA and inflammatory factor mRNA were evaluated by quantitive reverse transcription PCR (qRT-PCR); finally, the inhibitory effect of FFYH on the expression of coronavirus protein and its underlying mechanism against coronavirus were investigated by Western blot and immunofluorescence. Our results indicated that 50% toxic concentration (TC₅₀) FFYH on Huh7, Huh7.5, H460, and C3A cells were 2 035.21, 5 245.69, 2 935.28 and 520 µg·mL^-1, respectively; 50% inhibitory concentration (IC₅₀) of FFYH on HCoV-229E in Huh7 and Huh7.5 cells were 438.16 and 238.54 µg·mL^-1 with safety index (SI) of 4.64 and 21.99, respectively; IC₅₀ of FFYH on HCoV-OC43 in H460 cells was 165.13 µg·mL^-1 with SI of 17.78. Moreover, FFYH not only could inhibit the replication of coronaviruses (HCoV-OC43 and HCoV-229E) through inhibiting the transcription of viral RNA and the expression of viral protein, but also effectively suppress the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) at mRNA level caused by coronaviruses, which might be associated with the inhibitory effect of FFYH on mitogen-activated protein kinase (MAPK) pathway and the nuclear translocation of nuclear transcription factor-κB (NF-κB). In summary, our results demonstrated that FFYH exhibited a good in vitro anti-coronavirus effect, which provides a theoretical basis for its clinical use in the treatment of anti-coronavirus pneumonia.

This paper clarified the scientific connotation of the changes in cold and heat properties of Arisaematis Rhizoma and Arisaema Cum Bile through investigating the changes of substance and energy metabolism after drug intervention in the rats with normal and cold/heat syndrome, so as to improve the method of evaluating the drug properties of Chinese medicine. After one week of adaptive feeding, healthy male SD rats were randomly divided into three parts: normal rats, heat syndrome rat models, and cold syndrome rat models. Through ice water bath and oral euthyrox(120 μg·kg~(-1)), the models of cold syndrome and heat syndrome were induced, respectively. The models were made at 9:00 am. and administrated by gavage at 3:00 pm. every day. All administration groups were administrated with Arisaematis Rhizoma and Arisaema Cum Bile decoction, respectively, and the blank group was given the same dose of normal saline. After continuous administration for 15 d, the rats were anesthetized by chloral hydrate, blood was taken from abdominal aorta, and the hearts and livers were removed and stored at-80 ℃. The changes in the body weight and anal temperature of rats during administration were detected, and the liver coefficient of rats was detected after removing the liver. Enzyme-linked immunosorbent assay(ELISA) was adopted to detect the expression level of the indexes related to substance and energy metabolism in liver and heart of rat, and Western blot was used to detect the expression of key proteins in AMPK/mTOR signaling pathway for further verification. The results showed that Arisaematis Rhizoma enhanced the expression level of enzymes related to substance and energy metabolism in the normal and cold and heat syndrome rat models, and increased anal temperature, which exhibited warm(hot) drug property. Arisaema Cum Bile inhibited the level of substance and energy metabolism in rats, and reduced anal temperature, which showed cold(cool) drug property. Chinese Pharmacopoeia has recorded "Arisaematis Rhizoma has warm property and Arisaema Cum Bile has cool property", which is consistent with the phenomenon in this study. Therefore, it is feasible to evaluate the drug properties of Chinese medicine based on the substance and energy metabolism of normal and cold/heat syndrome model rats, which completes the method of evaluating drug properties of Chinese medicine.
AMP-Activated Protein Kinases ; Animals ; Arisaema/chemistry* ; Bile ; Chloral Hydrate ; Cold-Shock Response/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism ; Heat Stroke/therapy* ; Hot Temperature ; Male ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; Syndrome ; TOR Serine-Threonine Kinases ; Thyroxine ; Water