1.Efficacy and Safety of Qihuang Acupuncture Theory Combined with Opioid Analgesics in the Treatment of Moderate to Severe Cancer Pain in Lung Cancer Patients:a Randomize-Controlled Trial
Yingqi WANG ; Ruifang YU ; Jinpeng HUANG ; Guiya LIAO ; Ziyan GAN ; Zhenhu CHEN ; Xiaobing YANG ; Chunzhi TANG
Journal of Traditional Chinese Medicine 2025;66(4):358-366
ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group, with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain, short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group, administered once every other day, with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity, measured using the numerical rating scale (NRS) before and after treatment, and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) score, and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests, including routine blood, urine, stool, liver function, and kidney function, were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial, and both groups showed a decrease in average NRS scores and PS scores after treatment, with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group (P<0.05 or P<0.01). After treatment, the NRS change rate in the Qihuang acupuncture group was (0.42±0.17), significantly higher than that in the control group (0.14±0.27, P<0.01). The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group (P<0.01). The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30, and a decrease in symptom scores for fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and financial difficulties. In contrast, overall health status and constipation scores in the control group increased, while scores of fatigue, nausea and vomiting, pain, and appetite loss decreased (P<0.05 or P<0.01). After treatment, the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group (P>0.05), while the control group showed a significant increase in the 24-hour dose (P<0.01). No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study, the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% (1/33), while the incidence in the control group was 27.27% (9/33) and 36.36% (12/33), respectively, with the Qihuang acupuncture group showing significantly lower incidence (P<0.01). No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life, reduce the dose of opioid analgesics, and has good safety.
2.Evaluation of analgesic effect of nalbuphine in patients with non-mechanical ventilation in intensive care unit: a multi-center randomized controlled trail
Yi ZHOU ; Shaohua LIU ; Song QIN ; Guoxiu ZHANG ; Yibin LU ; Xiaoguang DUAN ; Haixu WANG ; Ruifang ZHANG ; Shuguang ZHANG ; Yonggang LUO ; Yu FANG ; Xiaoyun FU ; Tao CHEN ; Lening REN ; Tongwen SUN
Chinese Journal of Emergency Medicine 2024;33(1):59-64
Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.
3.Investigation of Efficacy and Mechanism of Zukamu Granules on Hypoxic Pulmonary Hypertension
Ruiqi LIU ; Tianyi YUAN ; Ranran WANG ; Ruifang ZHENG ; Difei GONG ; Shoubao WANG ; Jianguo XING ; Guanhua DU ; Lianhua FANG
Herald of Medicine 2024;43(4):550-560
Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.
4.Applications of Micro-Indicators in Syndrome Differentiation and Treatment of Traditional Chinese Medicine Based on the Trinity Life View of Body,Qi,and Spirit
Zhibin WANG ; Yang WANG ; Weijie HUANG ; Wen TANG ; Kang TONG ; Ruifang LIU ; Candong LI
Journal of Traditional Chinese Medicine 2024;65(4):337-340
The microcosmic syndrome differentiation is expounded from the the trinity life view of the body, qi, and spirit. This article analysed the relationship between micro-indicators and body, qi and spirit, considering that the abnormalities of micro-indicators in pathological states involve three different levels in terms of body, qi and spirit, and may reflect the degree of malfunction of body, qi and spirit and the dynamic changes of the focus during different pathological processes.Accordingly, based on the syndrome differentiation and treatment of traditional Chinese medicine, it is proposed that the macroscopic and the microscopic, the local and the whole, as well as the imbalance of body, qi and spirit reflected by microscopic and macroscopic indicators at different stages of disease should be combined to determine the corresponding treatment, thereby restoring the “harmony of body and spirit” of the human body.
5.The water-soluble TF3 component from Eupolyphaga sinensis Walker promotes tibial fracture healing in rats by promoting osteoblast proliferation and angiogenesis
Binghao Shao ; Xing Chen ; Jin' ; ge Du ; Shuang Zou ; Zhaolong Chen ; Jing Wang ; Huaying Jiang ; Ruifang Lu ; Wenlan Wang ; Chunmei Wang
Journal of Traditional Chinese Medical Sciences 2024;11(2):245-254
Objective:
To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability.
Methods:
A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels.
Results:
Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.
Conclusion
TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.
6.Establishment and analysis of an early prognosis model of patients with acute kidney injury in intensive care unit
Yu'an GENG ; Congmei WANG ; Zhijing XU ; Lu QI ; Yangang SHI ; Shiqiong SU ; Kai WANG ; Ruifang LIU
Chinese Critical Care Medicine 2024;36(2):178-182
Objective:To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance.Methods:A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI.Results:A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHEⅡ score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day " n", with y = 1.246?2 x1.164?9 and an R2 of 0.860?1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day " n", with y = -0.260?6 x2+3.010?7 x-1.612 and an R2 of 0.998?9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 μmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. Conclusion:The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.
7.Effect and significance of Wenyang Qudu formula on serum inflammatory factors and immune index in patients with severe infections
Zhijing XU ; Congmei WANG ; Yu'an GEN ; Lu QI ; Yangang SHI ; Huiming ZHANG ; Ying ZHANG ; Yihang ZHONG ; Ruifang LIU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):20-23
Objective To explore effect of Wenyang Qudu formula on serum inflammatory factors and immune index in patients with severe infections.Methods A total of 86 severe infection patients admitted to the Third People's Hospital of Henan Province from January to December 2023 were selected as the research subjects.According to the patient file order,odd numbers were the study group,and even numbers were the control group,with 43 cases in each group.The control group was treated with cefoperazone sulbactam sodium,while the study group was treated with Wenyang Qudu formula in addition to the control group[drug composition:Prepared aconite(first decocted)30 g,Poria cocos 30 g,White peony 15 g,Red peony 15 g,Stir fried atractylodes macrocephala 30 g,Dried ginger 9 g,Roasted licorice 9 g,Cassia twig 15 g,Semen lepidii 15 g,Dragon's bone 15 g,Raw oyster 15 g,Codonopsis pilosula 12 g,Angelica sinensis 12 g,Asarum 3 g,Schisandra chinensis 6 g,and Jujube 12 g].Brew in water,and took one dose daily,once in the morning and once in the evening,for a continuous period of 7 days.The differences in the scores of traditional Chinese medicine symptoms such as fever,dyspnea,frequent urination,urgency,and degree of sputum production,serum levels of interleukin-10(IL-10),C-reactive protein(CRP),eosinophils(EOS),and immune function indicators[immunoglobulin E(IgE),CD3+,CD4+,CD8+,CD4+/CD8+]were compared between two groups after treatment,and observed the occurrence of adverse reactions.Results After treatment,the traditional Chinese medicine symptom scores(fever,dyspnea,frequent urination and urgency,degree of sputum production),as well as IL-10,CRP,EOS levels,IgE,and CD8+ were significantly reduced in both groups compared to before treatment,CD3+,CD4+,and CD4+/CD8+ were significantly increased compared to before treatment.In addition,the study group had significantly lower scores of fever,dyspnea,frequent urination and urgency,degree of sputum production,IL-10,CRP,EOS levels,IgE,and CD8+ compared to the control group(fever score:1.36±0.30 vs.2.57±0.46,dyspnea score:1.22±0.31 vs.2.26±0.75,urinary frequency and urgency score:1.30±0.39 vs.2.33±0.82,degree of sputum production:1.19±0.77 vs.2.51±0.85,IL-10(ng/L):9.03±1.67 vs.10.51±2.40,CRP(mg/L):4.68±1.33 vs.7.82±2.53,EOS(×109/L):0.30±0.04 vs.0.46±0.10,IgE(mg/L):104.62±10.73 vs.135.68±14.64,CD8+:0.228±0.016 vs.0.258±0.020,all P<0.05],the levels of CD3+,CD4+,and CD4+/CD8+ were significantly higher than those in the control group(CD3+:0.636±0.044 vs.0.567±0.055,CD4+:0.537±0.054 vs.0.397±0.045,CD4+/CD8+:1.76±0.51 vs.0.55±0.39,all P<0.05].After treatment,it was discovered that the study group had not experienced any adverse reactions,while the control group had 1 case of nausea and vomiting and 1 case of chest tightness.There was no statistically significant difference in the incidence of adverse reactions between the study group and the control group[0(0/43)vs.0.05%(2/43),P>0.05].Conclusion The Wenyang Qudu formula can reduce the serum factor levels of IL-10,CRP,and EOS in critically infected patients,and improve immune function with good safety.
8.Diagnostic value of 18F-FDG and 18F-DTBZ PET/CT imaging for Parkinson′s disease with rapid eye movement sleep behaviour disorder
Meng YANG ; Xinyu WANG ; Ruifang WANG ; Yanpeng LI ; Qingzhu WANG ; Ruihua WANG ; Ping CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(8):449-455
Objective:To investigate the characteristics of 18F-FDG and 18F-9-fluoropropyl-(+ )-dihydrotetrabenazine (FP-(+ )-DTBZ; short for DTBZ) brain vesicular monoamine transporter type 2 (VMAT2) PET/CT imaging and analyze its clinical diagnostic value in Parkinson′s disease (PD) patients with or without rapid eye movement sleep behaviour disorder (RBD). Methods:From July 2022 to June 2023, 50 patients clinically confirmed with primary PD who underwent 18F-FDG and 18F-DTBZ PET/CT imaging in the First Affiliated Hospital of Zhengzhou University were prospectively collected. Among them, 18 patients with PD accompanied by RBD (PD-RBD(+ ) group; 16 males, 2 females, age (59.2±9.3) years); 32 patients without RBD (PD-RBD(-) group; 16 males, 16 females, age (57.7±10.2) years). Moreover, 10 healthy controls matched with the age of PD patients were included (5 males, 5 females, age (60.3±9.6) years). 18F-DTBZ specific uptake ratio (SUR) of bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra and other brain regions were obtained with occipital cortex as the reference region. Striatal anterior-posterior gradient and other related semi-quantitative indicators were calculated according to the corresponding formula. One-way analysis of variance (the least significant difference (LSD)- t test), Kruskal-Wallis rank sum test (Bonferroni correction), independent-sample t test and Mann-Whitney U test were used to analyze the data. Pearson correlation and Spearman rank correlation analyses were used to evaluate the correlations. ROC curve analysis was also performed. The differences in global glucose metabolism in two groups were compared using statistical parametric mapping (SPM). Results:PD-RBD(+ ) group had a significantly lower Mini-Mental State Examination (MMSE) or PD Sleep Scale (PDSS) score than PD-RBD(-) group ( z values: -3.12, -3.08, both P<0.01), and its contralateral striatal anterior-posterior gradient of the predominantly affected limbs was significantly lower than that in PD-RBD(-) group ( t=-2.73, P=0.009). SPM analysis showed that the glucose metabolism in the contralateral prefrontal lobe was higher than that in the PD-RBD (-) group ( t values: 3.11-3.57, all P<0.001). 18F-DTBZ SUR in the bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra were considerably lower in both groups compared to the healthy control group ( F values: 6.24-147.61, H values: 8.66-24.43, all P<0.05; post-hoc: LSD- t test, Bonferroni correction, all P<0.01). In the PD-RBD(-) group, contralateral striatal anterior-posterior gradient were negatively correlated with unified PD Rating Scale (UPDRS) score and modified Hoehn-Yahr (mH-Y) stage ( r=-0.35, P=0.048; rs=-0.39, P=0.026). The AUC for distinguishing PD-RBD(+ ) and PD-RBD(-) with a contralateral striatal anterior-posterior gradient was 0.706 (95% CI: 0.562-0.851, P=0.016), with the sensitivity and specificity of 59.4%(19/32) and 16/18, respectively. Conclusions:The decrease of contralateral striatal anterior-posterior gradient of VMAT2 is more obvious in patients with PD-RBD(+ ), and there are differences in brain metabolism between the two groups, suggesting that there may be different neuropathological changes and different pathophysiological mechanisms between PD patients with and without RBD. 18F-DTDZ PET/CT can provide imaging basis for the differential diagnosis of the disease subtypes.
9.Progress of selenium and its compounds in leukemia
Shuwen ZHANG ; Ruifang ZHU ; Hongwei WANG
Journal of Leukemia & Lymphoma 2024;33(5):313-316
Selenium is one of the essential trace elements in human body, which plays an important role in regulating human growth and physiological function. Selenium deficiency can lead to a variety of diseases, such as Kashin-Beck disease, Keshan disease, thyroid disease and increase the incidence of cancer. It was found that serum selenium level decreased significantly in patients with leukemia, and it was associated with poor prognosis. Selenium can play a dual role in the treatment of leukemia: on the one hand, it can play a synergistic anti-leukemia effect with chemotherapy drugs, and on the other hand, it can reduce the side effects of chemotherapy drugs. In recent years, nano-selenium, as a new type of elemental selenium, has higher bioavailability, stronger bioactivity and lower toxicity than organic and inorganic selenium. This article reviews the progress of selenium and its compounds in leukemia.
10.Analysis of the regional distribution differences of common variations of the MMACHC gene in cblC methylmalonic acidemia patients
Yuxin DENG ; Lili HAO ; Si DING ; Yi DING ; Wenjuan QIU ; Huiwen ZHANG ; Lili LIANG ; Kaichuang ZHANG ; Yi YANG ; Ruifang WANG ; Xuefan GU ; Lianshu HAN
Chinese Journal of Pediatrics 2024;62(11):1076-1082
Objective:To analyze regional differences in MMACHC gene variations among patients with cblC-type methylmalonic acidemia (MMA) in China and to explore the relationship between these variations and neonatal screening, biochemical markers and prognosis.Methods:Retrospective case summary. Clinical and laboratory data, including general condition, biochemical markers and genetic analysis, were collected from 1 859 cblC MMA patients from 2005 to 2023. Patients were divided into 7 groups according to their regions: north China, northeast China, east China, central China, south China, southwest China and northwest China. They were also classified into neonatal screening and non-neonatal screening groups. Mann-Whitney U and Kruskal-Wallis tests were used to compare biochemical marker levels. In contrast, the Chi-square test was applied to compare MMACHC gene variant frequencies, neonatal screening proportion, onset age and prognosis between groups. Results:Among 1 859 cases of cblC MMA, 1 019 were male and 840 were female, with a consultation age of 1.0 (0.1, 5.0) month. A total of 1 787 cases carried compound heterozygous or homozygous variants and only 1 variant site was identified in 72 cases. The 10 most frequent variants were c.609G>A (1 238 cases), c.658_660delAAG (343 cases), c.80A>G (284 cases), c.482G>A (239 cases), c.567dupT (191 cases), c.656_658delAGA (131 cases), c.217C>T (109 cases), c.394C>T (105 cases), c.445_446delTG (51 cases) and c.1A>G (50 cases). The frequency of the c.609G>A was the lowest in northwest China (28.8% (44/154), χ2=-18.42, P<0.05). The frequency of the c.567dupT was the most common in southwest China (25.0% (20/80), χ2=71.70, P<0.001) and c.656_658delAGA had the highest frequency in northeast China (9.3% (19/205), χ2=32.08, P<0.001). Non-missense variants (91.2% (62/68), 88.5% (46/52)) and early-onset patients (90.0% (36/40), 94.4% (34/36)) were both more prevalent in southwest and south China ( χ2=14.95, 31.69, both P<0.05). The proportion of neonatal screening was the lowest in south China (22.2% (8/36), χ2=98.48, P<0.05), where the mortality rate was the highest (19.1% (4/21), χ2=38.98, P<0.001). East China exhibited the highest frequency of missense variants (21.5% (339/1 579)), the highest proportion of patients identified through neonatal screening (54.5% (465/853)), and a more significant proportion of patients with good prognosis (36.6% (227/621), χ2=14.57, 93.49, 38.98, all P<0.05). In addition, the c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods (8.3% (132/1 586) vs. 5.9% (122/2 060), χ2=7.97, P<0.05). Conclusions:The frequency of MMACHC gene variation varies across different regions. The c.609G>A was least frequent in northwest China, c.567dupT was most common in southwest China, and c.656_658delAGA was most prevalent in northeast China. South China had the lowest neonatal screening rate and the highest mortality. At the same time, east China exhibited the highest frequency of missense variants, the highest proportion of patients identified through neonatal screening and the best prognosis. The c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods.


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