The patient was a girl, aged 10 years, who was admitted due to fever for 5 days and pancytopenia in peripheral blood for 2 days. Bone marrow examination showed the presence of phagocytic activity, and peripheral blood tests showed pancytopenia, an increase in ferritin, a reduction in fibrinogen, increases in triglyceride and sCD25, and a reduction in natural killer cell activity, which led to the diagnosis of hemophagocytic lymphohistiocytosis (HLH). On the day of admission, the child developed convulsions and rapidly progressed to refractory status epilepticus, which was consistent with the manifestations of febrile infection-related epilepsy syndrome. HLH was controlled after active immunotherapy, with the sequela of refractory epilepsy, and her cognitive function was essentially within normal limits. This article reports the condition of febrile infection-related epilepsy syndrome caused by HLH for the first time in China, in order to improve the awareness of this disease among clinicians.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Female ; Child ; Epilepsy/etiology* ; Fever/etiology* ; Epileptic Syndromes/etiology*

OBJECTIVE: To analyze the distribution of thalassemia (referred to as "thalassemia") gene variant types in the population of the Wuhan area, aiming to provide a genetic basis for the precise prevention and control as well as clinical diagnosis of thalassemia in the Wuhan region. METHODS: In this study, 2 133 suspected thalassemia patients and individuals undergoing prenatal screening who visited the Department of Hematology, Obstetrics and Gynecology, Reproductive Medicine, Pediatrics, and Neurology at Wuhan First Hospital from October 2022 to October 2024 were selected as the research subjects. Peripheral blood samples were collected from the patients. The common 27 thalassemia genotypes of α- and β-thalassemia were initially screened using fluorescence PCR melting curve analysis technology. For samples where the fluorescence PCR melting curve results indicated unknown variants or where the clinical phenotype was inconsistent with the common genotypes, Sanger sequencing technology was used for review and verification. RESULTS: Among the 2 133 specimens analyzed, common thalassemia gene variants were detected in 210 cases (9.85%, 210/2 133). A total of 156 cases (8.05%, 156/1 938) of thalassemia gene variants were detected in females and 54 cases (27.69%, 54/195) in males. A total of 94 cases (4.41%, 94/2 133) of α-thalassemia were detected, including 46 cases (2.16%, 46/2 133) of silent α-thalassemia, 47 cases (2.20%, 47/2 133) of mild α-thalassemia, and 1 case (0.05%, 1/2 133) of intermediate α-thalassemia. Additionally, 111 cases of β-thalassemia were identified (5.20%, 111/2 133), including 51 cases of β/β⁺ thalassemia (2.39%, 51/2 133), 59 cases of β/β⁰ thalassemia (2.77%, 59/2 133), and 1 case of β⁺/HbE thalassemia (0.05%, 1/2 133). αβ-composite thalassemia gene variants were detected in 5 cases (0.23%, 5/2 133), including 1 complex variant with a genotype of --^SEA/αα combined with CD41-42 (-TTCT) and 29(A>G), representing a heterozygous variant of three genotypes. Rare globin gene variants were detected in 3 cases, including HBB:c.60C>T, HBB:c.-146G>T, and HBA2:c.*12G>A. CONCLUSION The Wuhan region exhibits a relatively high prevalence of thalassemia genes with notable gender disparities. While maintaining focus on thalassemia screening for females, enhanced males screening efforts and genetic counseling should be implemented in future prevention programs.
Humans ; Female ; Male ; Genotype ; beta-Thalassemia/genetics* ; China ; Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Genetic Variation

OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

OBJECTIVE: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro. METHODS: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo. RESULTS: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05). CONCLUSION Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals ; Sirtuin 1/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Autophagy/drug effects* ; Male ; Intestinal Mucosa/drug effects* ; Rats, Sprague-Dawley ; Epithelial Cells/metabolism* ; Colon/drug effects* ; Humans ; Kidney Failure, Chronic/drug therapy* ; Signal Transduction/drug effects* ; Renal Dialysis ; Rats ; Kidney/drug effects*

Objective To investigate the effect of large artery atherosclerosis(LAA)and non-LAA subtypes on the efficacy of Ginkgo Diterpene Lactone Meglumine(GDLM)in patients with acute ischemic stroke.Methods This was a post-hoc analysis of multicenter,randomized,double-blind,placebo-controlled,and parallel-group trial.A total of 3 448 patients who had acute ischemic stroke were randomly assigned in a 1∶1 ratio to receive the injection of GDLM or the placebo once day within 48 h after symptoms and continued for 14 d.The primary outcome was the proportion of patients with a modified Rankin Scale(mRS)of 0 or 1 on day 90 after randomization.Results A total of 3 448 patients were enrolled,with 1 604(46.52% )patients with non-LAA and 1 844(53.48% )with LAA.Compared to the placebo treatment.GDLM injection effectively improve the functional prognosis,with a higher proportion of mRS score of 0-1 in both non-LAA(OR=1.24,95% CI:1.02-1.51;P=0.03)and LAA(OR=1.37,95% CI:1.14-1.65;P<0.001)group.There was no significant interaction between LAA subtypes with treatment(P=0.48 for interaction).Conclusion Among patients with acute ischemic stroke in this randomized clinical trial,GDLM might improve the favorable clinical outcomes at 90 d compared with placebo,regardless of LAA subtypes.Nevertheless,it is necessary to confirm the findings in the future.

Breast cancer remains a substantial threat to women's health and is one of the most prevalent malignant tumors in women.Because breast cancer onset is closely associated with female physiological characteristics,this article proposes that breast cancer be classified as a"women's miscellaneous diseases"and that its treatment be explored from this perspective.Drawing from Chapter 8 on Golden Chamber of Prescriptions for Miscellaneous Diseases in Women of Synopsis of Golden Chamber,the initial pathogenesis of breast cancer is associated with"emotional stress,improper lifestyle,deficiency,cold,and stagnation."The fundamental mechanism behind its formation is"blood cold accumulation and hardened masses."Specifically,emotional imbalance and improper lifestyle habits contribute to the combined invasion of the uterus by"deficiency,""accumulated cold,"and"stagnant qi."Over time,"cold-blood stasis accumulates at the uterine ostium,"and the cold and the stasis ascends from the uterus along the thoroughfare and conception vessels,obstructing the breast collaterals.This combination of yang qi stagnation and yin cold congealment,ultimately leads to the development of breast cancer.The treatment principle should focus on"activating yang and dispersing cold."A therapeutic approach centered on Wenjing Decoction combined with Xiaoyao Powder can be adapted based on the stage and type of breast cancer while also considering the dynamic interplay between pathogenic factors and healthy qi,along with shifts in deficiency and excess patterns of disease.By adhering to the principles of consistency and flexibility and integrating disease and syndrome differentiation,the goal is to develop precise and personalized treatment strategies to improve clinical outcomes.

Objective To investigate the effect of large artery atherosclerosis(LAA)and non-LAA subtypes on the efficacy of Ginkgo Diterpene Lactone Meglumine(GDLM)in patients with acute ischemic stroke.Methods This was a post-hoc analysis of multicenter,randomized,double-blind,placebo-controlled,and parallel-group trial.A total of 3 448 patients who had acute ischemic stroke were randomly assigned in a 1∶1 ratio to receive the injection of GDLM or the placebo once day within 48 h after symptoms and continued for 14 d.The primary outcome was the proportion of patients with a modified Rankin Scale(mRS)of 0 or 1 on day 90 after randomization.Results A total of 3 448 patients were enrolled,with 1 604(46.52% )patients with non-LAA and 1 844(53.48% )with LAA.Compared to the placebo treatment.GDLM injection effectively improve the functional prognosis,with a higher proportion of mRS score of 0-1 in both non-LAA(OR=1.24,95% CI:1.02-1.51;P=0.03)and LAA(OR=1.37,95% CI:1.14-1.65;P<0.001)group.There was no significant interaction between LAA subtypes with treatment(P=0.48 for interaction).Conclusion Among patients with acute ischemic stroke in this randomized clinical trial,GDLM might improve the favorable clinical outcomes at 90 d compared with placebo,regardless of LAA subtypes.Nevertheless,it is necessary to confirm the findings in the future.

AIM To investigate the clinical effects of Supplemented Jiao'ai Decoction combined with warm acupuncture and moxibustion on patients with endometriosis due to Congealing Cold with Blood Stasis.METHODS Eighty-six patients were randomly assigned into control group(43 cases)for 3-menstrual cycle intervention of warm acupuncture and moxibustion,and observation group(43 cases)for 3-menstrual cycle intervention of both Supplemented Jiao'ai Decoction and warm acupuncture and moxibustion.The changes in clinical effects,TCM syndrome scores,dysmenorrhea degree indices(VAS score,PGE2,PGF2α),hemodynamic indices(RI,PI),sexhormones(E2,FSH,LH),inflammatory factors(IL-1β,IL-6,TNF-α)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,dysmenorrhea degree indices,hemodynamic indices,sexhormones and inflammatory factors(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with endometriosis due to Congealing Cold with Blood Stasis,Supplemented Jiao'ai Decoction combined with warm acupuncture and moxibustion can safely and effectively regulate sexhormone levels,endometrial hemodynamics,inhibit inflammatory responses,and alleviate dysmenorrhea symptoms.

Breast cancer remains a substantial threat to women's health and is one of the most prevalent malignant tumors in women.Because breast cancer onset is closely associated with female physiological characteristics,this article proposes that breast cancer be classified as a"women's miscellaneous diseases"and that its treatment be explored from this perspective.Drawing from Chapter 8 on Golden Chamber of Prescriptions for Miscellaneous Diseases in Women of Synopsis of Golden Chamber,the initial pathogenesis of breast cancer is associated with"emotional stress,improper lifestyle,deficiency,cold,and stagnation."The fundamental mechanism behind its formation is"blood cold accumulation and hardened masses."Specifically,emotional imbalance and improper lifestyle habits contribute to the combined invasion of the uterus by"deficiency,""accumulated cold,"and"stagnant qi."Over time,"cold-blood stasis accumulates at the uterine ostium,"and the cold and the stasis ascends from the uterus along the thoroughfare and conception vessels,obstructing the breast collaterals.This combination of yang qi stagnation and yin cold congealment,ultimately leads to the development of breast cancer.The treatment principle should focus on"activating yang and dispersing cold."A therapeutic approach centered on Wenjing Decoction combined with Xiaoyao Powder can be adapted based on the stage and type of breast cancer while also considering the dynamic interplay between pathogenic factors and healthy qi,along with shifts in deficiency and excess patterns of disease.By adhering to the principles of consistency and flexibility and integrating disease and syndrome differentiation,the goal is to develop precise and personalized treatment strategies to improve clinical outcomes.