Objective To evaluate the efficacy and safety of single-used flexible ureteroscope lithotripsy(FURL)in the treatment of 2.0-3.0 cm non-lower-pole renal stones in elderly patients.Methods A total of 78 elderly patients with non-lower-pole renal stones measuring 2.0-3.0 cm admitted to our hospital were included in this study.Based on the surgical procedure,the patients were divided into the FURL group(42 cases of FURL with holmium laser lithotripsy)and the MPCNL group[36 cases of minimally invasive percutaneous nephrolithotomy(MPCNL)with holmium caser lithotripsy].Various parameters including operation time,stone fragmentation time,postoperative decrease of hemoglobin(Hb)level,postoperative Visual Analog Scale(VAS)for pain,hospitalization duration,stone-free rate(SFR)at 1 week and 4 weeks after surgery,secondary surgery rate,and incidence of complications were compared between the two groups.Results All the patients successfully underwent surgery.The decrease of Hb in the FURL group was(4.4±1.6)g/L,significantly lower than that in the MPCNL group[(24.7±4.6)g/L,t=-25.342,P=0.000].The postoperative VAS scores of the FURL group was(1.6±0.4)points,significantly lower than that of the MPCNL group[(5.6±0.9)points,t=-25.642,P=0.000].The stone fragmentation time in the FURL group was(82.5±10.2)min,significantly longer than that in the MPCNL group[(53.8±8.4)min,t=13.437,P=0.000].The operation time in the FURL group was(98.3±12.5)min,and there was no statistically significant difference compared to the MPCNL group[(96.7±11.8)min,t=0.555,P=0581].The hospitalization time in the FURL group was(3.5±1.5)d,significantly shorter than that in the MPCNL group[(8.6±1.7)d,t=-13.947,P=0.000].The incidence of complications in the FURL group was 26.2％(11/42),and there was no significant difference compared to the MPCNL group[27.8％(10/36),x2=0.025,P=0.875].The proportion of secondary treatment in the FURL group was 19.0％(8/42),and there was no significant difference compared to the MPCNL group[11.1％(4/36),x2=0.938,P=0.333].At 1 week after surgery,the SFR of the FURL group was 54.8％(23/42),significantly lower than that of the MPCNL group[86.1％(31/36),x2=8.943,P=0.003].At 4 weeks after surgery,there was no significant difference in SFR between the FURL group[90.5％(38/42)]and the MPCNL group[91.7％(33/36),x2=0.000,P=1.000].Conclusions Single-used flexible ureteroscope lithotripsy is highly effective in the treatment of non-lower-pole renal stones measuring 2.0-3.0 cm in elderly patients.It offers advantages such as minimal invasion,rapid recovery,minimal bleeding,low incidence of complications,and shorter hospitalization duration,which is worthy of promotion.

Objective Through the study of different grades for Atractylodis macrocephalae Rhizoma decoction pieces,improve the quality evaluation method,and provide theoretical basis for the classification of Atractylodis macrocephalae Rhizoma.Methods According to the traditional classification,the Atractylodis macrocephalae Rhizoma decoction pieces was divided into three grades.By HPLC and UV method,the determination of atractylodes lactone Ⅰ,Ⅱ,Ⅲ and the content of total polysaccharide for 36 batches of different grades of Atractylodis macrocephalae Rhizoma decoction pieces.According to the 2020 edition of Chinese pharmacopoeia,the correlation between the appearance traits of different grades of Atractylodis macrocephalae Rhizoma decoction pieces and the internal quality control indexes was analyzed.Results According to the appearance characters,multiple quality control index of content determination,through the principal component analysis,cluster analysis and so forth.The quality of first-grade decoction pieces of Atractylodis macrocephalae Rhizoma is significantly better than the second-grade and third-grade decoction pieces(P<0.05),and there is no significant difference between second-grade and third-grade decoction pieces(P>0.05).As a result,the Atractylodis macrocephalae Rhizoma decoction pieces can be divided into two grades,different grades with the content of atractylodes lactone and total polysaccharide were positively correlated.Conclusion The classification of Atractylodis macrocephalae Rhizoma decoction pieces based on multiple quality control indexes combined with appearance characters can provide a scientific basis for the quality control and grade study of this decoction piece.

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL^-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g^-1) and jaceosidin (4.17 ± 0.18 mg·g^-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).
Antifungal Agents/chemistry* ; Arthrodermataceae ; Artemisia/chemistry* ; Molecular Docking Simulation ; Mitochondria ; Microbial Sensitivity Tests

Objective The monosaccharide composition of Abelmoschus Manihot Radix polysaccharide was identified and then we evaluated the therapeutic effect on slow transit constipation.Finally,the pharmacodynamic substances and molecular mechanisms in the polysaccharide from Abelmoschus Manihot Radix to improve slow transit constipation were explored by network pharmacology and molecular docking techniques.Methods The polysaccharide from Abelmoschus Manihot Radix has been prepared by aqueous-alcoholic precipitation and has been determined by HPAEC method;The mice model of slow transit constipation was made by sc loperamide(10 mg?kg-1)and the therapeutic effect for the treatment of constipation was evaluated by two indicators:fecal water content and small intestinal propulsion rate;Pathological changes in the colon tissue of STC mice were observed by HE.Immunohistochemical method was used to detect zonula occludens-1(ZO-1)and claudin-1 expression in colon tissue of STC mice;qRT-PCR method was used to detect mRNA expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 in each group;Network pharmacology and molecular docking technology were used to explore the potential targets and pathways of the polysaccharide from Abelmoschus Manihot Radix in treating slow transit constipation.Results The Polysaccharide from Abelmoschus Manihot Radix significantly increased fecal water content and intestinal propulsion rate in mice caused by slow transit constipation,decreased the expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 mRNA(P<0.01,P<0.001),protected the integrity of the colonic barrier in STC mice,and increased the protein expressions of ZO-1 and claudin-1 in colon tissues of STC mice.By network pharmacology,it was found that monosaccharides such as rhamnose,fucose and glucuronic acid could mainly act on key targets such as STAT3,JUN,CASP3,HSP90AA1,VEGFA and IL-1β and regulate the Inflammatory mediator regulation of TRP channels,EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications to improve the symptoms of constipation in mice.Western blot results showed that intervention with polysaccharides from the roots of Solanum palmatum significantly reduced the expression of CASP3,VEGFA and IL-1β protein in the colon tissue of constipated mice.Conclusion The polysaccharide from Abelmoschus Manihot Radix can treat slow transit constipation through multi-component,multi-target and multi-pathway therapy.It provides a scientific basis for the further clinical application of Abelmoschus Manihot and drug development(National patent ZL202310894613.3.has been authorized)and it is expected to promote the efficient utilisation of resources from the non-medicinal parts of Abelmoschus Manihot.

Objective The monosaccharide composition of Abelmoschus Manihot Radix polysaccharide was identified and then we evaluated the therapeutic effect on slow transit constipation.Finally,the pharmacodynamic substances and molecular mechanisms in the polysaccharide from Abelmoschus Manihot Radix to improve slow transit constipation were explored by network pharmacology and molecular docking techniques.Methods The polysaccharide from Abelmoschus Manihot Radix has been prepared by aqueous-alcoholic precipitation and has been determined by HPAEC method;The mice model of slow transit constipation was made by sc loperamide(10 mg?kg-1)and the therapeutic effect for the treatment of constipation was evaluated by two indicators:fecal water content and small intestinal propulsion rate;Pathological changes in the colon tissue of STC mice were observed by HE.Immunohistochemical method was used to detect zonula occludens-1(ZO-1)and claudin-1 expression in colon tissue of STC mice;qRT-PCR method was used to detect mRNA expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 in each group;Network pharmacology and molecular docking technology were used to explore the potential targets and pathways of the polysaccharide from Abelmoschus Manihot Radix in treating slow transit constipation.Results The Polysaccharide from Abelmoschus Manihot Radix significantly increased fecal water content and intestinal propulsion rate in mice caused by slow transit constipation,decreased the expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 mRNA(P<0.01,P<0.001),protected the integrity of the colonic barrier in STC mice,and increased the protein expressions of ZO-1 and claudin-1 in colon tissues of STC mice.By network pharmacology,it was found that monosaccharides such as rhamnose,fucose and glucuronic acid could mainly act on key targets such as STAT3,JUN,CASP3,HSP90AA1,VEGFA and IL-1β and regulate the Inflammatory mediator regulation of TRP channels,EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications to improve the symptoms of constipation in mice.Western blot results showed that intervention with polysaccharides from the roots of Solanum palmatum significantly reduced the expression of CASP3,VEGFA and IL-1β protein in the colon tissue of constipated mice.Conclusion The polysaccharide from Abelmoschus Manihot Radix can treat slow transit constipation through multi-component,multi-target and multi-pathway therapy.It provides a scientific basis for the further clinical application of Abelmoschus Manihot and drug development(National patent ZL202310894613.3.has been authorized)and it is expected to promote the efficient utilisation of resources from the non-medicinal parts of Abelmoschus Manihot.

Humans ; Teas, Herbal/analysis* ; Beverages/analysis* ; Tea ; Liver Neoplasms

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Objective To determine the effects of oxygen at varied concentrations on in vitro maturation (IVM)of oocytes,and subsequent fertilization,early-stage development of embryos by collecting the human imma-ture oocytes from assisted reproduction treatment. Methods Immature oocytes were randomly allocated to be cul-tured with oxygen at a lower or higher concentration. Intracytoplasmic sperm injection of mature oocytes after IVM , the rates of maturation,fertilization,embryo cleavage and high quality embryo were investigated. Results The GV oocytes cultured with oxygen at the lower concentration yielded higher maturation and fertilization rates than those at the higher concentration(P<0.05). There were no significant differences in the rates of embryo cleavage and high quality embryo between two groups(P > 0.05). For MI oocytes,the maturation rate of oocytes cultured with oxygen at the lower concentration was higher as compared to that at the higher concertration (P < 0.05). There were no significant differences in the rates of fertilization ,embryo cleavage and high quality embryo between the two groups(P > 0.05). Conclusions Oxygen at a lower concentration is beneficial to IVM of human imma-ture oocytes and it also improves the fertilization of GV oocytes after IVM. Oxygen at a lower concentration has no beneficial effect on the embryo cleavage rate and high quality embryo rate.

Objective To explore the feasibility of high-frequency ultrasound detecting median nerve (MN) in type 2 diabetes mellitus(T2DM)with diabetic peripheral neuropathy(DPN).Methods Forty-two healthy volunteers were included as control group(Group A).Eighty-eight T2DM patients were divided into two groups according to symptoms,signs and electrophysiological results:with DPN (group C,46 patients) and without DPN (Group B,42 patients).The width(W),thickness(T) and cross-sectional area(CSA) of MN at 6 points [the wrist crease,pisiform bone,hamate bone,the 6 cm proximal to the wrist crease,the 4 cm proximal to tip of the medial epicondyle(ME) and the midpoint of the humerus] were evaluated.ROC curve was plotted to determine clinical diagnostic value of three lines on six points in diagnosis of DPN. Results ①Comparing with Group A,the width(P <0.05) except for the 4 cm proximal to tip of ME and the midpoint of the humerus,the thickness (P <0.05) except for the 4 cm distal to ME and CSAs of all points were enlarged in DPN patients(P <0.001).The width(P <0.05)at the wrist crease,hamate bone and the midpoint of the humerus,the thickness (P <0.01) at the wrist crease and pisiform bone,CSAs (P <0.01) of all sites except for the wrist crease were increased in Group B.Comparing Group B with C, the width at the wrist crease,the thickness in the midpoint of the humerus,CSAs except for the 4 cm proximal to ME and the midpoint of the humerus were dramaticlly increased in Group C(P <0.001).②A diagnostic value comparison:when diagnostic value of W,T and CSA at six points is the most predictive, the sensitivity is 80.4%,84.8%,84.8% respectively and specificities are all 54.8%.Diagnostic value of CSA and T is superior to the width.The CSA and T of the hamate bone level were the most predictive of DPN.The corresponding optimal cut-off value was 0.097 cm 2 ,0.233 cm respectively.Conclusions The backbone and the abnormal changes of different lines of the MN in DPN can be observed by high-frequency ultrasound.The width and thickness of the MN at six points are increased in different degree,but CSAs of all levels can enlarge.When diagnostic value of W,T and CSA at six points is the most predictive for DPN, the sensitivity is superior to specificity respectively.The CSA and T of the hamate bone levelare the most predictive for the evaluation of DPN.

Objective To explore the nonlinear complexity characteristics of electroencephalogram (EEG) in ischemic stroke patients with different course. Methods Sample entropy of all bands of EEG signals in 20 ischemic stroke patients and 10 healthy controls was extracted and analyzed using statistical analysis methods. Results The full-band EEG in sample entropy of stroke patients was significantly lower than that of healthy controls in most locations. Theα-band sample entropy of different course had significant differences in the frontal, temporal and occipital lobe (P<0.05), and the parameters had significant negative linear correlation with the post-stroke time in some locations. Conclusions There is an abnormal neural electrical activity in post-stroke patients. It is feasible to detect the aberrant EEG complexity using sample entropy, which is worth of further research.