Flexible ureteral lithotripsy (FURL) under general anesthesia (GA) is the dominant method in the treatment of renal and upper ureteral calculi，but some patients cannot tolerate GA.In recent years，there has been a growing interest in the use of local anesthesia (LA) as a safe and effective alternative.And it is also an option for patients who have calculi ≤20 mm with high fragility，lower CT value and better compatibility.Before surgery，it is important to conduct relevant examinations，evaluate the status of patients，prevent infections，and indwell ureteral stents.During surgery，lithotomy position，scissors position，prone leg position and other positions should be selected according to the specific conditions of patients.LA drugs should be used to control physiological pain and relieve psychological anxiety.Patients' breathing state should be carefully monitored，and appropriate ureteroscope and lens sheath should be selected for the success and safety of the operation.In this paper，the perioperative management of FURL under LA is briefly summarized，so as to provide reference for clinical practice.

Objective To study anti-inflammatory activities of oridonin derivatives without Michael fragment. Methods Two oridonin sulfonylureas were designed and synthesized by a photocatalysis reaction and a scaffold hopping strategy. The inhibitory rate of IL-1β was selected for anti-inflammatory activity evaluation. Results Both compound ZM658 and ZM659 revealed potent anti-inflammatory activities with the values of 69.3% and 59.7% in THP-1 cells, respectively. Moreover, two compounds also showed dose-dependent and low cytotoxicity. Conclusion The result indicated that Michael receptor fragment of oridonin could be substituted with sulfonylurea group.

Objective To study the antitumor activities of RRx-001 derivatives with novel covalent fragments. Methods Four targeted compounds were designed and synthesized. The structures were confirmed by ¹H NMR and HRMS. A549 and HCT116 cancer cell lines were selected for antiproliferative activity assays. Results All the compounds revealed antitumor activities and compound ZM528 showed the best antitumor activity against these two cell lines with IC₅₀ values of （5.1±4.8） μmol/L and （6.0±2.7） μmol/L, respectively. Conclusion The result indicated that bromoacetyl group of RRx-001 could be substituted with other covalent fragments.

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for simultaneous determination of seven characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rat plasma, including galangin, kaempferol, kaempferide, pinocembrin, 1,7-diphenyl-4-en-3-heptanone, 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA), and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4-en-3-heptanone(DPHB). The new developed HPLC-MS/MS method was applied to study the pharmacokinetics of the 7 characteristic components in rats with Helicobacter pylori gastritis. A Waters Sunfire C_(18) column(2.1 mm×150 mm, 3.5 μm) was used. The acetonitrile-aqueous solution(containing 0.1% formic acid) was adopted as the mobile phase for gradient elution. Seven components and internal standard(chlorogenic acid) were separated within 12 min. Mass spectrometric detection was performed in multiple reaction monitoring(MRM) mode using electrospray ionization(ESI) source with fast switching between positive and negative ions. The method was verified by specificity, linearity, precision, accuracy, recovery, matrix effect, and stability and met the requirements of pharmacokinetic study on the 7 components in rat plasma. Pharmacokinetic results showed that the average peak time(T_(max)) of the 7 components was 0.31-2.19 h, their elimination half-life(t_(1/2)) was 5.26-16.65 h, and the average residence time(MRT) was 6.29-31.03 h after the oral administration of the active fraction of Alpiniae Officinarum Rhizoma to rats with H. pylori gastritis. The plasma exposure levels of galangin and DHPA were higher than those of the other components. The concentration-time curves of four detected flavonoids showed obvious double peaks. This study elucidated the pharmacokinetic characteristics of 7 characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rats with H. pylori gastritis, providing a scientific basis for the identification of the pharmacodynamic substances of Alpiniae Officinarum Rhizoma for treatment of H. pylori gastritis and the clinical application of Alpiniae Officinarum Rhizoma in the prevention and treatment of H. pylori gastritis.
Animals ; Rats ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Helicobacter pylori/drug effects* ; Alpinia/chemistry* ; Rats, Sprague-Dawley ; Gastritis/metabolism* ; Helicobacter Infections/metabolism* ; Flavonoids/blood* ; Rhizome/chemistry* ; Liquid Chromatography-Mass Spectrometry

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

A 4-year-old boy was admitted to the hospital with a 3-day history of rash and intermittent abdominal pain, during which abnormal results from routine blood tests were discovered. Initially, he presented with acute jaundice hepatitis and pancytopenia. The patient's condition progressed rapidly, with recurrent fever, worsening jaundice of the skin and sclera, and progressively worsening hepatosplenomegaly. Liver function impairment and bone marrow failure continued to deteriorate, while cytokine levels continued to rise. After excluding infections, autoimmune diseases, tumors, genetic metabolic disorders, and toxicities, the patient was diagnosed with hepatitis-associated aplastic anemia (HAAA) complicated by hemophagocytic lymphohistiocytosis (HLH). Following treatment with corticosteroids, plasma exchange, intravenous immunoglobulin, and liver protection therapy, the patient's symptoms partially alleviated. Aplastic anemia complicated by HLH is relatively uncommon, and HAAA complicated by HLH is even rarer, often presenting insidiously and severely. This paper presents a case of HAAA complicated by HLH and summarizes previously reported cases in the literature, providing references for the early diagnosis and treatment of this condition.
Humans ; Lymphohistiocytosis, Hemophagocytic/therapy* ; Male ; Anemia, Aplastic/complications* ; Child, Preschool ; Hepatitis/complications*

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Objective:To investigate the outcomes of periacetabular osteotomy (PAO) through modified Smith-Petersen or Bikini approach with an auxiliary posterolateral incision for developmental dysplasia of hip (DDH).Methods:85 patients (97 hips) who underwent PAO through modified Smith-Petersen or Bikini approach with auxiliary posterolateral incision for DDH in the 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army or the Second Xiangya Hospital of Central South University from January 2016 to January 2021 were retrospectively analyzed. There were 70 females and 15 males, with an average age of 28.6±8.4 years (12-49). According to the Hartofilakidis classification, all patients were classified as type Ⅰ. There were 77 hips classified as Grade 0 and 20 hips classified as Grade 1 according to the T?nnis classification. The X-ray evaluation including the lateral central edge angle (LCEA), t?nnis angle (TNS) and anterior central edge angle (ACEA), visual analogue score (VAS) and modified Harries hip score (mHHS) were recorded preoperatively and during each postoperative follow-up. The cumulative sum (CUSUM) method was used to fit the learning curves of operation time.Results:All patients were followed-up with an average of 52.7±18.9 months (21 to 84). The average operative time and intraoperative blood loss were 95.9±28.2 min (65 to 215) and 414.7±97.0 ml (250 to 900), respectively. The learning curve of operation time was 10 cases. The average LCEA 32.39° (30.29°, 34.92°), TNS 3.14° (1.56°, 5.67°) and ACEA 31.55° (29.07°, 33.88°) were all significantly improved compared to preoperative values ( Z=-30.764, P<0.001; Z=30.595, P<0.001; Z=-38.134, P<0.001). The average VAS was reduced from 5.18±0.88 points preoperatively to 1.27±0.93 points postoperatively with significant difference ( t=51.231, P<0.001). The average mHHS was increased from 73.12±9.17 to 92.02±4.05 postoperatively with significant difference ( t=-26.902, P<0.001). No patients received total hip arthroplasty during the follow-up period. Conclusion:Bernese PAO through modified Smith-Petersen or Bikini approach with a small auxiliary posterolateral incision was not only a safe and effective method for the treatment of DDH but also shortened the learning curve and reduced difficulty of the surgery.

Objective To investigate the effect of acacetin on oxidative stress injury in diabetic cataract(DC)rats and its regulation of sirtuin 1(Sirt1)/adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway.Methods Sixty SD rats were randomly divided into the control group,model group,low-dose acacetin group,high-dose acacetin group,and acacetin+Sirt1 inhibitor(EX527)group.DC rat models were constructed except for the control group.Rats in the low-dose and high-dose acacetin groups were injected with 10 mg·kg-1 and 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day,respectively.Rats in the acacetin+EX527 group were injected with 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day;additionally,3.5 mg·kg-1 EX527 was administered subcutaneously through the osmotic micro-pump for 4 weeks.The same amount of nor-mal saline was pumped into rats in the rest groups for 4 weeks.After administration,blood pressure and fasting blood glu-cose(FBG)were measured.The lens opacity was observed under the slit lamp irradiation,and the histopathological chan-ges in the lens were observed after hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was performed to de-termine the serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),in-terleukin(IL)-6,and IL-1 β.Western blot was applied to detect the expression levels of Sirt1,phosphorylated AMPK(p-AMPK),AMPK,and Nrf2 proteins.Results Compared with the control group,the lens epithelial cells(LECs)of rats in the model group showed patchy and striped shapes,and migration and aggregation occurred;the systolic blood pres-sure(SBP),FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Compared with the model group,the migration and aggregation of LECs improved in the low-dose and high-dose acacetin groups,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β decreased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins increased(all P＜0.05).Compared with the high-dose acacetin group,the morphological chan-ges and aggregation of LECs in the acacetin+EX527 group were more significant,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Conclusion Acacetin may protect DC rats from oxidative stress injury by activating the Sirt1/AMPK/Nrf2 pathway.

Objective To investigate the effect of total flavone of Cydonia oblonga on oxidative damage of human lens epithelial cells induced by high glucose and its mechanism.Methods A cell injury model was established by inducing human lens epithelial cells with high glucose.Human lens epithelial cells were cultured in the medium containing 30 mmol·L-1 glucose for 24 h,which was recorded as the high glucose group.Cells in the control group were cultured in a medium con-tainning 5.5 mmol·L-1 glucose for 24 h.Human lens epithelial cells were inoculated into 96-well plates with 5 × 103 cells per well,and treated with mediums containing 10 mmol·L-1,20 mmol·L-1,and 40 mmol·L-1 total flavone of Cydonia ob-longa combined with 30 mmol·L-1 glucose for 24 h.They were recorded as high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total flavone of Cydonia oblonga group.Human lens epithelial cells were transfected with anti-miR-NC and anti-miR-370 with Lipo-fectamine2000 transfection reagent,and treated with 30 mmol·L-1 glucose for 24 h,which were recorded as high glucose+anti-miR-NC group and high glucose+anti-miR-370 group.Human lens epithelial cells were transfected with miR-NC and miR-370 mimics,and treated with medium containing 30 mmol·L-1 glucose and 40 mmol·L-1 total flavone of Cydonia oblonga for 24 h,which were labeled as high glucose+total flavone of Cydonia oblonga+miR-NC group and high glucose+total flavone of Cydonia oblonga+miR-370 group.The activities of superoxide dismutase(SOD)and cata-lase(CAT),and the content of malondialdehyde(MDA)were measured by Enzyme-linked immunosorbent assay;flow cy-tometry was applied to detect apoptosis rate;quantitative reverse transcription polymerase chain reaction was applied to detect the expression level of miR-370;Western blot was applied to detect the expression of apoptosis-related proteins.Results Compared with the control group,the activities of SOD and CAT decreased and the content of MDA increased in the human lens epithelial cells of the high glucose group,and the differences were statistically significant(all P＜0.05);compared with the high glucose group,the activities of SOD and CAT significantly increased and the content of MDA signifi-cantly decreased in the high glucose+low total flavone of Cydonia oblonga group,the high glucose+medium total fla-vone of Cydonia oblonga group and the high glucose+high total flavone of Cydonia oblonga group(all P＜0.05).Com-pared with the control group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of human lens epithelial cells in the high glucose group significantly increased(all P＜0.05);compared with the high glucose group,the apoptosis rate,Caspase-3 and Caspase-9 protein expressions of human lens epithelial cells in the high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total fla-vone of Cydonia oblonga group significantly decreased(all P＜0.05).The expression levels of miR-370 in human lens epi-thelial cells were 1.00±0.00,4.04±0.36,3.22±0.24,2.42±0.23 and 1.62±0.14 in the control group,high glucose group,high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblon-ga group,and high glucose+high total flavone of Cydonia oblonga group,respectively.There was a statistically different significance among the five groups(F=256.138,P＜0.05).Compared with the high glucose+anti-miR-NC group,the ex-pression of miR-370 significantly decreased,the activities of SOD and CAT significantly increased,and the content of MDA significantly decreased in human lens epithelial cells of the high glucose+anti-miR-370 group(all P＜0.001).Compared with the high glucose+anti-miR-NC group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of the hu-man lens epithelial cells in the high glucose+anti-miR-370 group significantly decreased(all P＜0.001).Compared with the high glucose+total flavone of Cydonia oblonga+miR-NC group,the activities of SOD and CAT significantly de-creased,and the content of MDA,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 significantly in-creased in the human lens epithelial cells of high glucose+total flavone of Cydonia oblonga+miR-370 group(all P＜0.001).Conclusion The expression of miR-370 increases in high glucose-induced human lens epithelial cells.Total fla-vone of Cydonia oblonga can inhibit the oxidative stress and apoptosis of high glucose-induced human lens epithelial cells,and the mechanism may be related to the decreased expression of miR-370.