ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

Background: Traditional Mongolian medicine utilizes complex herbal formulations for restoring bodily functions and treating various ailments. Sampilnorov, a traditional medicinal composition, is recognized for its therapeutic properties in regenerating one of the 17 qualities and 15 functions of the human body, particularly qi and its associated functions. Aim: This study aims to analyze the therapeutic potential of Sampilnorov in treating conditions related to vein disorders, fever, and musculoskeletal diseases. Materials and Methods: A literature review was conducted, focusing on the Mongolian Medicine section of the Medical Pharmacopoeia of the People’s Republic of China. The pharmacological properties, indications, and mechanisms of Sampilnorov were examined. Results: The findings suggest that Sampilnorov is a valid therapeutic system in Mongolian traditional medicine for addressing multiple physiological dysfunctions. Further clinical and pharmacological studies are necessary to validate its efficacy and mechanisms of action. Conclusion Sampilnorov pills are traditionally used for Eliminating chronic fever and lesions in the white veins, Removing yellow fluid accumulation, Treating disorders of the black and white veins, such as paralysis, gout, rheumatism, and typhoid fever, Healing damaged veins and alleviating symptoms of leprosy, kidney vein concussions, kidney heat, vein and tendon spasms, and joint sprains.

Background/Aims: Multiple rapid swallows (MRS) is a provocative test during high-resolution esophageal manometry (HRM) to evaluate contraction reserve (CR). This study aims to determine the prevalence of CR in patients with ineffective esophageal motility (IEM) and MRS performed in the upright position, and to assess the ideal number of MRS sequences. Methods: We enrolled adult patients diagnosed with IEM according to the Chicago classification version 4.0 who underwent HRM with 3 MRS sequences. Presence of CR was identified as either: the distal contraction integral (DCI) of the post-MRS sequence exceeding the mean DCI of single swallows (ratio > 1) or the mean DCI of the 3 post-MRS sequences surpassing the mean DCI of single swallows. The occurrence of CR was compared following 1, 2, and 3 MRS sequences. Results: When assessing CR in 57 patients referenced to mean single supine swallow DCI, the pooled prevalence of CR following 1, 2, and 3 MRS sequences was 23/57 (40.4%), 31/57 (54.4%), and 33/57 (57.9%), respectively. More patients had CR after 2 MRS sequences compared to 1 (P < 0.001), but there was no significant difference in CR between 2 and 3 MRS sequences (P = 0.160). More patients had CR after 2 (P = 0.013) and 3 MRS sequences (P = 0.034) when CR was referenced to single upright compared to single supine swallows. Conclusion Among patients with IEM, 58.0% had CR after 3 upright MRS sequences and 2 were adequate to assess CR.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Background/Aims: Multiple rapid swallows (MRS) is a provocative test during high-resolution esophageal manometry (HRM) to evaluate contraction reserve (CR). This study aims to determine the prevalence of CR in patients with ineffective esophageal motility (IEM) and MRS performed in the upright position, and to assess the ideal number of MRS sequences. Methods: We enrolled adult patients diagnosed with IEM according to the Chicago classification version 4.0 who underwent HRM with 3 MRS sequences. Presence of CR was identified as either: the distal contraction integral (DCI) of the post-MRS sequence exceeding the mean DCI of single swallows (ratio > 1) or the mean DCI of the 3 post-MRS sequences surpassing the mean DCI of single swallows. The occurrence of CR was compared following 1, 2, and 3 MRS sequences. Results: When assessing CR in 57 patients referenced to mean single supine swallow DCI, the pooled prevalence of CR following 1, 2, and 3 MRS sequences was 23/57 (40.4%), 31/57 (54.4%), and 33/57 (57.9%), respectively. More patients had CR after 2 MRS sequences compared to 1 (P < 0.001), but there was no significant difference in CR between 2 and 3 MRS sequences (P = 0.160). More patients had CR after 2 (P = 0.013) and 3 MRS sequences (P = 0.034) when CR was referenced to single upright compared to single supine swallows. Conclusion Among patients with IEM, 58.0% had CR after 3 upright MRS sequences and 2 were adequate to assess CR.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Background/Aims: Multiple rapid swallows (MRS) is a provocative test during high-resolution esophageal manometry (HRM) to evaluate contraction reserve (CR). This study aims to determine the prevalence of CR in patients with ineffective esophageal motility (IEM) and MRS performed in the upright position, and to assess the ideal number of MRS sequences. Methods: We enrolled adult patients diagnosed with IEM according to the Chicago classification version 4.0 who underwent HRM with 3 MRS sequences. Presence of CR was identified as either: the distal contraction integral (DCI) of the post-MRS sequence exceeding the mean DCI of single swallows (ratio > 1) or the mean DCI of the 3 post-MRS sequences surpassing the mean DCI of single swallows. The occurrence of CR was compared following 1, 2, and 3 MRS sequences. Results: When assessing CR in 57 patients referenced to mean single supine swallow DCI, the pooled prevalence of CR following 1, 2, and 3 MRS sequences was 23/57 (40.4%), 31/57 (54.4%), and 33/57 (57.9%), respectively. More patients had CR after 2 MRS sequences compared to 1 (P < 0.001), but there was no significant difference in CR between 2 and 3 MRS sequences (P = 0.160). More patients had CR after 2 (P = 0.013) and 3 MRS sequences (P = 0.034) when CR was referenced to single upright compared to single supine swallows. Conclusion Among patients with IEM, 58.0% had CR after 3 upright MRS sequences and 2 were adequate to assess CR.

[摘 要] 目的：探讨精氨酸-甘氨酸-天冬氨酸（RGD）修饰对肿瘤抑素19肽（T-19）抗肝癌活性的影响，比较分析T-19及RGD修饰的T-19（RGD-T-19）对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法：用Fmoc固相法合成T-19及RGD-T-19，用高效液相色谱仪和质谱进行分离、鉴定。常规培养SK-Hep-1细胞，用0、50、100、150、200、250 mg/mL的T-19及RGD-T-19分别处理细胞，分为0 mg/mL（对照）组、50 mg/mL组、100 mg/mL组、150 mg/mL组、200 mg/mL组、250 mg/mL组。CCK-8法、克隆形成实验、划痕愈合实验和Tanswell小室实验、WB法和qPCR法分别检测SK-Hep-1细胞的增殖、迁移、侵袭能力，以及环氧合酶-2（COX-2）、基质金属蛋白酶-2（MMP-2）、MMP-9、组织基质金属蛋白酶抑制剂-1（TIMP-1）、TIMP-2蛋白和MMP-1、MMP-2 mRNA的表达。结果：经质谱鉴定，用Fmoc固相法合成的T-19及RGD-T-19纯度高。T-19和RGD-T-19均能显著抑制SK-Hep-1细胞的增殖、迁移、侵袭能力，抑制COX-2蛋白、MMP-2和MMP-9蛋白及mRNA的表达、促进TIMP-1、TIMP-2蛋白的表达（P < 0.05, P < 0.01, P < 0.001），RGD-T-19的抑制或促进效应均明显强于T-19（均P < 0.05）。结论：利用Fmoc固相法合成了纯度高、活性好的T-19及RGD-T-19，两种肽均能抑制SK-Hep-1细胞增殖、侵袭和迁移能力，RGD-T-19作用明显强于T-19。