The cellular oxygen sensor factor inhibiting HIF (FIH) is a JmjC domain-containing 2-oxoglutarate and Fe(II)-dependent oxygenase that catalyzes the hydroxylation of specific asparagine residues in the C-terminal transcriptional activation domain of hypoxia-inducible factor (HIF)-α. This modification inhibits HIF transcriptional activity by suppressing its interaction with the transcriptional coactivator p300/CBP. FIH inhibitors have attracted considerable attention due to their potential metabolic regulatory capabilities, particularly their significant therapeutic potential in improving lipid metabolic disorders. This review provides a detailed discussion of the catalytic mechanism of FIH and its biological functions in regulating the HIF pathway. In addition, it highlights recent advances in the development of FIH inhibitors and further explores their potential applications in the treatment of lipid metabolic diseases, offering new insights for the development of drugs targeting lipid metabolism disorders.

Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Plant-derived natural products have long been a vital source for developing therapeutic drugs. Wedelolactone (WDL), a coumestan isolated from Eclipta prostrata, Wedelia calendulacea, Wedelia chinensis, and Sphagneticola trilobata, demonstrates a broad spectrum of therapeutic potential, including anticancer, anti-inflammatory, anti-obesity, anti-myotoxic, antimicrobial, anti-diabetic, and tissue-protective activities. This review synthesizes information on the isolation, total synthesis, pharmacological activity, underlying mechanisms, and pharmacokinetic properties of WDL. Additionally, it offers insights into potential clinical applications and future drug discovery avenues utilizing WDL or its derivatives, either independently or in combination with other pharmaceuticals.
Coumarins/isolation & purification* ; Humans ; Animals ; Biological Products/chemical synthesis* ; Molecular Structure ; Plant Extracts/chemical synthesis* ; Wedelia/chemistry* ; Eclipta/chemistry*

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

Objective To investigate the role of member septin family(SEPT12)in human spermatogenesis and its influence on sperm motility and sperm ultrastructure.Methods Whole exome sequencing(WES)was performed on peripheral blood DNA extracted from 375 patients with asthenoteratozoospermia,and a patient with idiopathic in-fertility carrying compound heterozygous mutation of SEPT12 was screened out.Sanger sequencing was performed to verify the mutation,and co-segregation analysis was performed in the family.The morphological abnormalities of sperm were analyzed by hematoxylin-eosin(HE)staining and scanning electron microscopy(SEM),and the ultra-structural defects of sperm were analyzed by transmission electron microscopy(TEM).Then the effects of the muta-tion on the level and position of the protein and the changes of the location and level of the defect structure markers were analyzed by Western blot and immune-fluorescence(IF).Results The compound heterozygous mutations c.C332A(p.Ti111K)and c.406_416 del TGCTCGTATTG(p.q136 VFS*39)in the SEPT12 gene were screened and identified in a patient with asthenoteratozoospermia.The mutations were verified by Sanger sequencing,which was consistent with the co-segregation genetic pattern of the family.The mutations resulted in loss of protein expres-sion,decreased sperm motility and sperm morphological deformities,mainly including short tail,curly tail and ir-regular sperm head.The ultrastructure of sperm showed that the annulus between the mid-piece and the principle-piece was missing,the acrosome membrane of sperm head fell off and the nucleus contained vacuoles.In the mid-piece of sperm flagella,the arrangement of mitochondrial sheath was disordered,most of flagella axoneme central pair was absent,microtubules doublet was missing or disordered,and some radical spoke was absent.By Western blot and IF,the marker proteins of related structural components were detected,and the results showed that the level of SEPT4 protein decreased,SEPT6 protein unchanged,acrosomal related proteins ACTL7A and ACROSIN protein missing,and the expression levels of mitochondrial and axoneme related proteins TOMM20,SPAG6 and RSPH3 protein significantly decreased.Conclusion The deletion of SEPT12 protein caused by SEPT12 gene mu-tation leads to the deletion of the annulus between the mid-piece and the principle-piece,and the abnormal assem-bly of sperm acrosome,mitochondrial sheath and flagella.