At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*

Objective To investigate the causal relationship between hyperthyroidism and systemic lu-pus erythematosus(SLE).Methods According to the current summary data of genome-wide association studies(GWAS),the screened single nucleotide polymorphism(SNP)was selected as the instrumental varia-bles,hyperthyroidism served as the exposure factor and SLE as the outcome variable,and the Mendelian ran-domization analysis(MR)analysis method was used for conducting the study.Among them,the inverse vari-ance weighting(IVW)was the main MR analysis method,the MR-Egger regression method was used to the test for horizontal pleiotropy,and the sensitivity adopted the leave-one-method test,and the MR results con-ducted the visualized analysis by scatter plot,forest plot and funnel plot.Results Ten valid SNP were screened.In the MR analysis,IVW supported a causal relationship between hyperthyroidism and SLE(OR=1.838,95%CI:1.302-2.593,P<0.001);the MR-egger regression method supported the relationship be-tween hyperthyroidism and SLE(OR=4.070,95%CI:1.961-8.449,P=0.003);in addition,the weighted median method also supported the relationship between hyperthyroidism and SLE(OR=1.685,95%CI:1.238-2.294,P<0.001).Conclusion There appears to be a causal relationship between hyperthyroidism and SLE.

Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.

Objective To explore the clinical efficacy and safety of intravenous thrombolysis and dual antiplatelet therapy in the treatment of acute mild non-disabling ischemic stroke.Methods A retrospective cohort study was conducted,including 138 patients with acute mild non-disabling ischemic stroke[National Institutes of Health Stroke Scale(NIHSS)score≤5]from January 2022 to March 2024,within 6 h of onset.Patients were divided into an intravenous thrombolysis group(66 cases)and a dual antiplatelet group(72 cases).Propensity score matching was used to match patients 1∶1,resulting in 44 patients in each group after matching.Demographic data,clinical data,clinical outcome indicators,and adverse events were collected.The primary outcome was defined as a good functional outcome[modified Rankin Scale(mRS)score 0-2]at 90 d post-onset.Secondary outcomes included NIHSS scores at 24 h,72 h,and 7 d post-onset;the proportion of early neurological deterioration;intracranial and systemic hemorrhagic events within 90 d post-onset;and death within 90 d.Results ①Before matching,the intravenous thrombolysis group had a lower age and admission mRS score than that of the dual antiplatelet group,with statistically significant differences(all P＜0.05).After matching,there were no statistically significant differences between the two groups in terms of age,gender,hypertension,diabetes,cardiac disease,atrial fibrillation,hyper low density lipoprotein-cholesterol(LDL-C),hyperhomocysteinemia,prior stroke,prior smoking,admission NIHSS score,admission mRS score,location of stroke and TOAST classification(all P＞0.05);②There was no statistically significant difference in the proportion of patients with a good functional outcome at 90 d post-onset and the mRS score at 90 d between the intravenous thrombolysis group and the dual antiplatelet group[88.6％(39/44)vs 93.2％(41/44),P=0.458,P=0.308];③ The intravenous thrombolysis group had significantly lower median NIHSS scores at 24 h and 72 h post-onset compared to the dual antiplatelet group,with statistically significant differences[1 vs 2.5,1 vs 2,P=0.018,0.043].There were no statistically significant differences in the other efficacy and safety outcomes.Conclusions Intravenous thrombolysis therapy can bring significant short-term benefits to patients with acute mild non-disabling ischemic stroke,helping to shorten the time to recovery to a good neurological functional outcome,and does not increase the risk of bleeding and mortality.However,in terms of good functional outcomes at 90 d post-onset,its effects are similar to those of dual antiplatelet therapy.Nevertheless,there is an urgent need for larger sample,higher quality clinical studies to further validate these findings.

Objective To explore the clinical efficacy and safety of intravenous thrombolysis and dual antiplatelet therapy in the treatment of acute mild non-disabling ischemic stroke.Methods A retrospective cohort study was conducted,including 138 patients with acute mild non-disabling ischemic stroke[National Institutes of Health Stroke Scale(NIHSS)score≤5]from January 2022 to March 2024,within 6 h of onset.Patients were divided into an intravenous thrombolysis group(66 cases)and a dual antiplatelet group(72 cases).Propensity score matching was used to match patients 1∶1,resulting in 44 patients in each group after matching.Demographic data,clinical data,clinical outcome indicators,and adverse events were collected.The primary outcome was defined as a good functional outcome[modified Rankin Scale(mRS)score 0-2]at 90 d post-onset.Secondary outcomes included NIHSS scores at 24 h,72 h,and 7 d post-onset;the proportion of early neurological deterioration;intracranial and systemic hemorrhagic events within 90 d post-onset;and death within 90 d.Results ①Before matching,the intravenous thrombolysis group had a lower age and admission mRS score than that of the dual antiplatelet group,with statistically significant differences(all P＜0.05).After matching,there were no statistically significant differences between the two groups in terms of age,gender,hypertension,diabetes,cardiac disease,atrial fibrillation,hyper low density lipoprotein-cholesterol(LDL-C),hyperhomocysteinemia,prior stroke,prior smoking,admission NIHSS score,admission mRS score,location of stroke and TOAST classification(all P＞0.05);②There was no statistically significant difference in the proportion of patients with a good functional outcome at 90 d post-onset and the mRS score at 90 d between the intravenous thrombolysis group and the dual antiplatelet group[88.6％(39/44)vs 93.2％(41/44),P=0.458,P=0.308];③ The intravenous thrombolysis group had significantly lower median NIHSS scores at 24 h and 72 h post-onset compared to the dual antiplatelet group,with statistically significant differences[1 vs 2.5,1 vs 2,P=0.018,0.043].There were no statistically significant differences in the other efficacy and safety outcomes.Conclusions Intravenous thrombolysis therapy can bring significant short-term benefits to patients with acute mild non-disabling ischemic stroke,helping to shorten the time to recovery to a good neurological functional outcome,and does not increase the risk of bleeding and mortality.However,in terms of good functional outcomes at 90 d post-onset,its effects are similar to those of dual antiplatelet therapy.Nevertheless,there is an urgent need for larger sample,higher quality clinical studies to further validate these findings.

Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.

OBJECTIVE To evaluate the clinical value of anlotinib in third-line treatment for patients with advanced non-small cell lung cancer(NSCLC)through real-world data.METHODS Clinical data of patients with advanced NSCLC who received treatment at the First Affiliated Hospital of Anhui University of Chinese Medicine from February 2021 to December 2024 were retrospectively collected.They were divided into anlotinib group(27 cases,receiving anlotinib therapy)and immunotherapy group(22 cases,receiving immunotherapy agents alone or in combination with chemotherapy drugs)according to treatment regimens.The progression-free survival(PFS)and overall survival(OS)of patients were compared between the two groups,and the occurrence of adverse drug reactions during the treatment period was recorded.Using a partitioned survival model,an economic evaluation of the two treatment regimens was conducted with a cost-utility analysis approach from the perspective of the healthcare system.RESULTS The median PFS and OS of patients in the anlotinib group were 5.93 months and 11.27 months,respectively;the median PFS and OS of patients in the immunotherapy group were 5.33 months and 9.77 months,respectively;the difference was not statistically significant(P＞0.05).There was no statistical difference in the total incidence of adverse drug reactions and grade 3-4 serious adverse drug reactions between the two groups(P＞0.05).Compared with the immunotherapy group,the incremental cost-effectiveness ratio of the anlotinib group was 1 806 724.60 yuan/quality-adjusted life year(QALY),which was significantly higher than three times China's per capita gross domestic product in 2024(287 247 yuan/QALY).CONCLUSIONS For third-line treatment of advanced NSCLC patients,the efficacy of anlotinib is no worse than that of immunotherapy alone or in combination with chemotherapy drugs,and the safety of the two groups is comparable.However,anlotinib is not cost-effective.

OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus (T2DM) insulin resistance (IR) rats.METHODS Sixty male SD rats were randomly divided into control group (12 rats) and modeling group (48 rats).The modeling group was fed with a high-fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1％ streptozotocin to establish T2DM IR model.The model rats were randomly divided into model group,the compatibility of Astragali Radix-Puerariae Lobatae Radix group[QG group,4.05 g/(kg·d),intragastric administration],ferroptosis inhibitor ferrostatin-1 group[Fer-1 group,5 mg/kg by intraperitoneal injection,once every other day],the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group[QG+erastin group,4.05 g/(kg·d) by intragastric administration+erastin 10 mg/(kg·d),intraperitoneal injection].After 4 weeks of intervention,serum fasting blood glucose (FBG) and fasting insulin (FINS) were measured in each group of rats,and homeostasis model assessment of insulin resistance (HOMA-IR) and the natural logarithm of insulin action index(IAI) were calculated;the serum levels of total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C),aspartate transaminase (AST) and alanine transaminase (ALT),Fe2+and Fe content,glutathione (GSH),malondialdehyde (MDA) and superoxide dismutase (SOD) levels,NADP+/NADPH ratio and reactive oxygen species (ROS) were determined.The pathological morphology of its liver tissue was observed;the protein expressions of glutathione peroxidase 4 (GPX4),ferritin heavy chain 1 (FTH1),long-chain acyl-CoA synthetase 3 (ACSL3),ACSL4,ferritin mitochondrial (FTMT),and cystine/glutamate anti-porter (xCT) in the liver tissue of rats were detected.RESULTS Compared with control group,the liver cells in the model group of rats showed disordered arrangement,swelling,deepened nuclear staining,and more infiltration of inflammatory cells,as well as a large number of hepatocyte vacuoles and steatosis;FBG (after medication),the levels of TC,TG,LDL-C,AST,ALT,FINS,MDA and ROS,HOMA-IR,Fe2+and Fe content,NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated,while the levels of HDL-C,GSH and SOD,IAI,protein expressions of GPX4,FTH1,ACSL3,FTMT and xCT were significantly reduced or down-regulated (P<0.01).Compared with the model group,both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators,the differences in the changes of most indicators were statistically significant (P<0.01 or P<0.05).Compared with QG group,the improvement of the above indexes of QG+erastin group had been reversed significantly (P<0.01).CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats,and alleviate IR degree,ion overload and pathological damage of liver tissue.The above effects are related to the inhibition of ferroptosis.

Objective:To discuss the effect of ligustilide on the cardiac function and angiogenesis in the rats with heart failure,and to clarify its regulatory effect on protein kinase D1(PKD1)/hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway.Methods:The SD rats were randomly divided into sham operation group,model group,ligustilide group,PKD1/HIF-1α/VEGF signaling pathway inhibitor CID755673(CID)group,and ligustilide+CID group.The heart failure rat model was established by ligation of the left anterior descending coronary artery.The rats in ligustilide group were injected intravenously with 20 mg·kg-1 ligustilide,the rats in CID group were injected intraperitoneally with 50 mg·kg-1 CID,and the rats in ligustilide+CID group were injected intraperitoneally with 50 mg·kg-1 CID followed by intravenous injection of 20 mg·kg-1 ligustilide,once per day for 4 consecutive weeks.The cardiac function indexes of the rats in various groups were detected by echocardiography;the percentages of myocardial infarction areas of the rats in various groups were detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining;the pathomorphology of myocardium tissue of the rats in various groups was observed by HE staining;the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in ischemic area of myocardium tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.Results:Compared with sham operation group,the rats in model group and CID group had altered myocardial cell morphology,increased intercellular gaps,disorganized arrangement,visible muscle fiber breaks and inflammatory cell infiltration;the rats in ligustilide group and ligustilide+CID group had relatively orderly myocardial fiber arrangement,fewer myocardial fiber breaks and decreased number of inflammatory cells.Compared with sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of the rats in model group were decreased(P<0.05),the left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD)were increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05).Compared with model group,the LVEF and LVFS of the rats in ligustilide group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05);compared with model group,the LVEF and LVFS of the rats in CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with ligustilide group,the LVEF and LVFS of the rats in ligustilide+CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with CID group,the LVEF and LVFS of the rats in ligustilide+CID group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05).Conclusion:Ligustilide can promote the angiogenesis,reduce the myocardium infarction area,and improve the cardiac function in the rats with heart failure;it works through activation of the PKD1/HIF-1α/VEGF pathway.

Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.