Objective:To investigate the protective effect of achyranthes bidentata(AB)on sperm quality in mice with sper-matogenic disorder through the glycolytic metabolic pathway and its action mechanism.Methods:We equally randomized 40 Kun-ming mice into a normal control,a model control,a low-dose AB(3.5 g/kg)and a high-dose AB group(7.0 g/kg),and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin(30 mg/kg).Two days after modeling,we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining,detection of perm motility with the sperm quality analyzer,examination of the apoptosis of testis cells by flow cytometry,measurement of the levels of testosterone(T),malondialdehyde(MDA),superoxide dismutase(SOD)and cata-lase(CAT)in the serum and testis tissue by ELISA,and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ(HK2),pyruvate kinase M2(PKM2),platelet phosphofructokinase(PFKP),lactate dehydrogenase A(LDHA)and the meiosis pro-teins REC8 and SCP3 by Western blot,and the mRNA expressions of glycolytic phosphofructokinase 1(PFK1),phosphoglycerate ki-nase 1(PGK1),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)by fluorescence quantitative PCR(FQ-PCR).Results:Compared with the model controls,the mice in the AB groups showed significant increases in the testis coefficient,kidney in-dex,sperm concentration,sperm motility,spermatogonia,primary spermatocytes,spermatids,sperm count and the serum T level(P＜0.05 orP＜0.01),but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm(P＜0.01).Achyranthes bidentata also significantly elevated the levels of SOD and CAT,and down-regulated the mRNA expressions of MDA,TNF-α and IL-1β(P＜0.05 or P＜0.01),and up-regulated the protein expressions of HK2,PKM2,PFKP,LDHA,REC8 and SCP3,and expressions of the glycolysis key genes Pfk1 and Pgk1(P＜0.05 orP＜0.01).Conclusion:Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.

To investigate the effects of phosphorus fertilizer on the morphological traits, active ingredients and rhizosphere soil microbial community of Polygala tenuifolia. The phosphorus fertilizer was calculated in terms of P_2O_5. Five treatments were set up: 0(CK), 17(P1), 34(P2), 51(P3), and 68(P4) kg per Mu(1 Mu≈667 m~2). A randomized block design was adopted. Samples of P. tenuifolia and its rhizosphere soil were collected under different superphosphate fertilizer treatments. Illumina high-throughput sequencing was used to analyze the rhizosphere soil microbial community, 9 morphological traits were measured and the content of 11 active ingredients were determined. The results showed that the whole plant weight, shoot fresh weight, root weight, and root peel thickness were the highest under P1 treatment, increasing by 34.41%, 38.80%, 39.21%, and 3.17% respectively compared to CK. Under P2 treatment, the plant height, stem diameter, root thickness, and core thickness were significantly higher than CK. Phosphorus fertilizer had a significant impact on the content of tenuifolin, sibiricose A5, sibiricose A6, arillanin A, 3,6'-disinapoyl sucrose, and polygalaxanthone Ⅲ. Correlation analysis results showed that the relative abundance of Arthrobacter, Bacillus, norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, MND1 and other bacteria, as well as the relative abundance of Neocosmospora, Paraphoma and other fungi were positively correlated with root diameter, wood core diameter, the whole plant weight, root weight, shoot fresh weight of P. tenuifolia. Bacillus, Neocosmospora, Subulicystidium were significantly positively correlated with oligosaccharides such as 3,6'-disinapoyl sucrose, sibiricose A5、sibiricose A6、glomeratose A、arillanin A and tenuifoliside C. Arthrobacter, Humicola, Aspergillus, Paraphoma were positively correlated with tenuifolin and norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, Fusarium were positively correlated with polygalaxanthone Ⅲ. Evidently, appropriate phosphorus application is conducive to the growth and quality improvement of P. tenuifolia, and can increase the abundance of beneficial microorganisms in the soil.
Rhizosphere ; Phosphorus/pharmacology* ; Soil Microbiology ; Polygala/anatomy & histology* ; Fertilizers/analysis* ; Bacteria/metabolism* ; Soil/chemistry* ; Microbiota/drug effects* ; Plant Roots/metabolism*

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Hypoplastic left heart syndrome is a congenital heart disease characterized by mitral and（or）aortic valve stenosis or atresia，leading to the hypoplasia of the left ventricle，ascending aorta and aortic arch.If not treated in time，most children die within a few weeks after birth.Congenital complete atrioventricular block is a rare congenital cardiac conduction disorder.When combined with severe cardiac malformations，the mortality rate is extremely high.In this case，a 26-year-old pregnant woman with a history of 3 pregnancies and 1 delivery，had a natural conception with monochorionic diamniotic twins. At 22 +5 weeks of gestation，it was first found that one of the twins had hypoplastic left heart syndrome with congenital complete atrioventricular block through fetal echocardiography detection.This situation was extremely rare，and there was a lack of clinical guidelines on how to manage the pregnancy and determine the time of delivery time.In this case，prenatal ultrasound was used to monitor and comprehensively evaluate fetal cardiac function through the cerebroplacental ratio（CPR）combined with the cardiovascular overall performance score（CVPS）.Pregnancy safety management was implemented，and a cesarean section was performed at an elective time.Another healthy fetus did not suffer any adverse effects. This case provides strong evidence for ensuring the safety of healthy fetus and mother in perinatal period.It is also confirmed that CPR and CVPS combined evaluation of fetal cardiac function and pregnancy outcome will be more accurate and comprehensive.This method is simple，accurate，non-invasive，and can be used as an effective method for clinical evaluation of fetal cardiac function.

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression. CONCLUSION The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans ; Multiple Myeloma/therapy* ; Middle Aged ; Male ; Female ; Aged ; Prognosis ; Immunoglobulin D ; Adult ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively. RESULTS: Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×10⁹ /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 ⁺ CD4^- CD8 ⁺), 6 cases were CD57 ⁺, 3 cases were TCRα/β ⁺, and 3 cases were TCRγ/δ ⁺. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving. CONCLUSION The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; Retrospective Studies

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Hypoplastic left heart syndrome is a congenital heart disease characterized by mitral and（or）aortic valve stenosis or atresia，leading to the hypoplasia of the left ventricle，ascending aorta and aortic arch.If not treated in time，most children die within a few weeks after birth.Congenital complete atrioventricular block is a rare congenital cardiac conduction disorder.When combined with severe cardiac malformations，the mortality rate is extremely high.In this case，a 26-year-old pregnant woman with a history of 3 pregnancies and 1 delivery，had a natural conception with monochorionic diamniotic twins. At 22 +5 weeks of gestation，it was first found that one of the twins had hypoplastic left heart syndrome with congenital complete atrioventricular block through fetal echocardiography detection.This situation was extremely rare，and there was a lack of clinical guidelines on how to manage the pregnancy and determine the time of delivery time.In this case，prenatal ultrasound was used to monitor and comprehensively evaluate fetal cardiac function through the cerebroplacental ratio（CPR）combined with the cardiovascular overall performance score（CVPS）.Pregnancy safety management was implemented，and a cesarean section was performed at an elective time.Another healthy fetus did not suffer any adverse effects. This case provides strong evidence for ensuring the safety of healthy fetus and mother in perinatal period.It is also confirmed that CPR and CVPS combined evaluation of fetal cardiac function and pregnancy outcome will be more accurate and comprehensive.This method is simple，accurate，non-invasive，and can be used as an effective method for clinical evaluation of fetal cardiac function.

Objective:To observe the effect and safety of the traditional Chinese medicine(TCM)Linggui Formula(LGF)in the treatment of asthenospermia with kidney deficiency and blood stasis.Methods:This randomized controlled trial included 90 ca-ses of asthenospermia with kidney deficiency and blood stasis treated in our hospital from September 2022 to September 2023,45 by oral medication with LGF(the trial group)and the other 45 with oral levocarnitine solution(the control group),all for 12 weeks.We followed up the patients for 12 weeks,recorded the semen parameters,TCM syndrome scores,sexual hormone levels,pregnancy rates,and DNA fragmentation index(DFI)of the patients,and compared them between the two groups before and after treatment.Re-sults:Totally,82 of the patients completed the study,42 in the trial and 40 in the control group.After treatment,the patients in the trial group showed significant increases in the percentage of progressively motile sperm(PMS)(from[19.25±3.08]% to[38.57±4.99]%,P<0.05),total sperm motility(from[32.29±3.64]% to[46.50±4.77]%,P<0.05)and sperm concentration(from[83.9±37.2]to[95.1±34.9]×106/ml],P<0.05),and so did the controls in PMS(from[19.75±4.28]% to[34.46±5.07]%,P<0.05),total sperm motility(from[33.02±4.93]% to[43.11±4.72]%,P<0.05)and sperm concen-tration(from[85.2±39.7]to[88.1±35.2]×106/ml,P<0.05),all even more significant in the trial than in the control group(P<0.05).No statistically significant difference was observed in the semen volume either in the trial(from[3.38±0.38]to[3.24±0.45]ml,P>0.05)or in the control group(from[3.46±0.52]to[3.30±0.37]ml,P>0.05),or between the trial and control groups(P>0.05),or in the sexual hormone levels,pregnancy rates,and sperm DFI between the two groups before and after treatment(P>0.05).Both groups of patients had good safety profiles without serious adverse reactions.Conclusion:Linggui Formula can improve the percentage of PMS in asthenospermia patients with kidney deficiency and blood stasis,potentially enhancing pregnancy rates and with a good safety.