OBJECTIVE To investigate the effect of Guanxinning tablets(GXN) on early heart failure model rats, and to explore the protective mechanism of GXN on heart failure rats from the perspective of intestinal flora. METHODS Six rats who underwent sham operation were set as sham operation group. Took 80 SD rats to undergo aortic arch stenosis and established a heart failure rat model. The surviving rats were divided into 4 groups, namely the model control group, the positive control group(captopril tablets 12.5 mg·kg–1), high-dose and low-dose of GXN group(600, 1 200 mg·kg–1). The 4 groups were administered continuously for 8 weeks. Cardiac ultrasonography was performed every 4 week. Serum NT-proBNP, hs-CRP, IL-6, TNF-α, SOD and MDA levels were measured. The effects of GXN on the structure and function of intestinal flora were observed based on the high-throughput sequencing technology and bioinformatics analysis of 16S gut microbiome. RESULTS Compared to the model control group, after giving different doses of GXN, the survival rate of rats increased, and the thickness of the ventricular wall decreased to varying degrees. The weight of the heart and coefficient of the heart were all reduced. GXN could also reduce the level of inflammatory factors, inhibit the level increase of NT-proBNP in rats, and increase the activity of serum SOD. In addition, GXN intervention could significantly improve the intestinal flora diversity of rats with heart failure, the possible target genera of GXN were Akkermansia genera, Phascolarctobacterium genera and Oxalobacter genera. The effect of GXN on intestinal function in rats with heart failure might be concentrated in non-homologous end-joining, influenza A, carotenoid synthesis, indole alkaloids biosynthesis, betalain biosynthesis, renin-angiotensin system and other biological pathways. CONCLUSION The protective effect of GXN on early heart failure rats may be related to the regulation of intestinal flora pathway.

Objective To explore the risk factors of orthostatic hypotension(OH)in patients with multiple system atrophy(MSA).Methods A total of 199 MSA patients were included,and they were divided into groups based on the severity of OH.The data differences between the groups were compared,and the risk factors for the occurrence of OH in MSA patients were analyzed from ordered Logistic regression.Results There were significant differences in gender,diabetes,disease grade,syncope,supine hypertension,fatigue and brain protective drugs among patients with different OH grades(all P＜0.05).Ordered Logistic regression analysis found that disease grade(probable MSA),syncope,supine hypertension,and fatigue were independent risk factors for the occurrence of OH in MSA patients(all P＜0.05).Conclusions OH is commonly present in MSA patients,and its severity is influenced by many factors.Disease grade(probable MSA),syncope,lying hypertension and fatigue are independent risk factors of OH in patients with MSA.

Objective:To analyze clinical characteristics of acromegaly patients who have discordant growth hormone(GH) or insulin-like growth factor-1(IGF-1) levels and evaluate impact of different GH cut-offs on discordance rate.Methods:A retrospective analysis was conducted on data from 66 acromegaly patients treated at Nanjing Drum Tower Hospital from November 2017 to March 2023. Patients were categorized based on the nadir GH(GHn) and IGF-1 levels at the last follow-up into four groups: controlled, high GH, high IGF-1, and active. Clinical and metabolic parameters were compared across these groups, and impact of different GHn and fasting growth hormone(GHf) cut-offs on discordance rate was evaluated.Results:No statistically significant differences were observed among groups in age, duration of follow-up, imaging characteristics(all P>0.05). High IGF-1 group had higher fasting insulin and homeostasis model assessment for β cell function compared to controlled and high GH group(all P<0.05), while these parameters did not differ between high GH and controlled group. High IGF-1 group had higher carboxy-terminal cross-linked telopeptide of type 1 collagen, osteocalcin and procollagen type 1 N-terminal propeptide compared to controlled and high GH group, but differences were not statistically significant(all P>0.05). These parameters also did not differ between high GH and controlled group. Discordance rate was not significantly different when GHn cut-offs was 1.0 μg/L or 0.4 μg/L(30.3% vs 21.3%, P=0.146). Compared to 2.5 μg/L, discordance rate was lower when GHf cut-off was 1.0 μg/L(39.4% vs 24.3%, P=0.041). Conclusion:The discordance rate in treated acromegaly patients during follow-up is approximately 30%. Different GH measurement timings and cut-offs significantly impact discordance rate. Patients with normal GH and elevated IGF-1 levels are at potential risk of active disease, and require closer follow-up. This study provides a valuable reference for treatment of patients with discordant GH and IGF-1 levels.

Purpose: Neoadjuvant chemotherapy is strongly recommended for advanced gastric cancer due to good local control and a high rate of R0 dissection with this strategy. Minimally invasive techniques such as laparoscopy-assisted or total laparoscopic approaches is becoming more and more acceptable in the treatment for gastric cancer. However, the safety and efficiency of total laparoscopic D2 gastrectomy (TLG) for advanced gastric cancer after neoadjuvant chemotherapy have not been well evaluated. Methods: A retrospective study in a single center from 2014 to 2016 was conducted. A total of 65 locally advanced gastric cancers were treated by laparoscopy-assisted gastrectomy (LAG) or TLG. Parameters which include operation time, blood loss, complications, hospital stay, 3-year overall survival, and 3-year disease-free survival were used for comparison. Results: The time of operation in the TLG group was shorter than in the LAG group (P = 0.013), blood loss was less (P = 0.002) and time to first flatus was shorter (P = 0.039) in the TLG group than that in the LLG group. Intraoperative and postoperative complications were comparable in both groups. No significant difference was found in 3-year overall and disease-free survival. Conclusion For patients with locally advanced gastric cancer after neoadjuvant chemotherapy, laparoscopic D2 gastrectomy can be considered as a safe and efficient alternative. A further multicenter prospective randomized controlled study is needed to elucidate the applicability of this technique for advanced gastric cancer.

Objective:To establish an isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the determination of L-tryptophan and its metabolites in serum.Methods:The methodology was established and evaluated using serum samples collected from 166 healthy subjects undergoing physical examinations at West China Hospital from November 2022 to January 2023 were collected. Isotope-labeled markers of L-tryptophan (Trp), L-kynurenine (Kyn), and kynurenic acid (KA) were used as internal standards. After protein precipitation treatment of serum samples, LC-MS/MS was used to determine Trp, Kyn, and KA simultaneously. The selectivity, specificity, linearity, detection limit (LOD), quantification limit (LOQ), carry-over, precision, recovery rate, matrix effect, and dilution integrity of the method were evaluated.Results:The linearity of Trp, Kyn, and KA was demonstrated to be 0.999. The LODs were 0.10 μmol/L, 0.01 μmol/L and 1.00 nmol/L, respectively. The LOQs were 0.20 μmol/L, 0.04 μmol/L and 2.00 nmol/L, respectively. The intra-batch precision and inter-batch precision were below<10%. The average recovery rate and the relative matrix effect were all about 100%. The samples over the upper limit of quantitation can be diluted up to 16 times. The Trp concentration, Kyn concentration, KA concentration, Kyn/Trp ratio, and KA/Kyn ratio in serum of healthy subjects were 59.55±10.92 μmol/L, 1.85±0.43 μmol/L, 39.89±17.93 nmol/L, (31.64±8.19)×10 -3 and 21.51±6.72, respectively. Conclusion:An ID-LC-MS/MS method was successfully established for the quantitative determination of Trp, Kyn, and KA in serum. The method proved to be simple, rapid, sensitive, accurate, and reliable, providing robust support for clinical research related to these analytes.

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g^-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

Objective To evaluate the efficacy and safety of high intensity focused ultrasound(HFIU)combined with endometrial ablation in the treatment of adenomyosis(AM)patients with heavy menstrual bleeding(HMB).Method A total of 199 patients with AM combined with HMB who underwent HIFU treatment at the Obstetrics and Gynecology Center of Affiliated Hospital of Chengdu University of TCM from July 2020 to September 2022 were selected and divided into two groups according to the ablation range.The combined ablation group included 80 cases with lesion and endometrial ablation(endometrial ablation rate≥30%),while the lesion ablation group 119 cases with simple lesion ablation.A 1∶1 propensity score matching was performed on the two groups,resulting in 59 patients in each group.A 6-month follow-up was conducted.The clinical manifestations(menstrual volume,degree of dysmenorrhea,uterine and lesion volume),quality of life(MS-QOL,UFS-QOL),and postoperative adverse reactions between the two groups before and 6 months after surgery was compared.Results Menstrual volume,degree of dysmenorrhea,uterine and lesion volume,MS-QOL score,and UFS-QOL score of the both groups were improved 6 months after surgery,when compared to those before surgery(P<0.05).Significantly reduced menstrual volume,degree of dysmenorrhea,and lower MS-QOL score were observed in the combined ablation group when compared with the lesion ablation group(P<0.05),but there was no statistical significance in uterine and lesion volume and UFS-QOL score(P>0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05),but the combined ablation group had longer vaginal bleeding and fluid flow time(P<0.05).Conclusion The combined HIFU and endometrial ablation can effectively reduce menstrual flow,alleviate dysmenorrhea,and improve quality of life in patients with AM combined with HMB.Although it increases vaginal bleeding and fluid flow time,reasonable symptomatic management can effectively prevent the occurrence of adverse consequences such as infection.

Objective:This study aims to analyze the efficacy and safety of anlotinib in the real world for patients with unresectable or metastatic bone and soft-tissue sarcomas(STSs). Methods:Clinical data of 124 patients with unresectable or metastatic bone and STSs treated with anlotinib in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed.Information on age,sex,performance status,lines of anlotinib,surgical history,reduction of anlotinib,adverse reaction,metastatic site,tumor location,pathological subtypes and combination chemotherapy was collected and analyzed.The objective response rate(ORR)and disease control rate(DCR)was analyzed for short-term efficacy.Kaplan-Meier method was performed for survival analysis,and the evaluation indexes were median progression-free survival(mPFS)and median overall survival(mOS). Results:The main pathological subtypes of 124 patients were Synovial sarcoma(SS),Leiomyosarcoma(LMS),liposarcoma(LPS).The median age was 48.5 years(9-83 years).The ORR and DCR of anlotinib used in first-line therapy were 26.8％and 82.1％,but in second-line therapy and beyond,the ORR and DCR only were 5.9％and 64.7％.There were improvement in mPFS and mOS with anlotinib in first-line therapy compared to second-line therapy and beyond(mPFS:22.0 months vs 7.0 months,P=0.001;mOS:51.0 months vs 32.0 months,P=0.035).Adverse reactions of anlotinib were well tolerated,and the main grades of adverse reactions were grade Ⅰ and Ⅱ.No new anlotinib-related adverse reactions were identified. Conclusion:Anlotinib has shown a definite effect in the treatment of unresectable or metastatic bone and STSs.The adverse events of anlotinib are minor and well tolerated,and the efficacy of first-line treatment is better.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing. METHODS: Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing. RESULTS: Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis. CONCLUSION Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.
Child ; China ; DNA Copy Number Variations ; Electron Transport ; Humans ; Mutation ; NADH Dehydrogenase/genetics* ; Pedigree

Objective To compare the clinical effects of interscalene brachial plexus block and superior trunk block in arthroscopic shoulder surgery with 0.25% ropivacaine. Methods 46 patients undergoing shoulder arthroscopy surgery were included and randomly divided into group ISB (n=23) and group ST (n=23). Patients in group ISB received 10 ml 0.25% ropivacaine on the lateral side of C5 and C6. Patients in group ST were treated with 5 ml 0.25% ropivacaine on both sides of the superior trunk of brachial plexus. The diaphragmatic excursion, Numerical Rating Scale(NRS), duration of the block, handgrip strength were recorded at different time. Results No statistical difference was detected between the two groups in the reduction of diaphragmatic excursion within 30 min after block (P>0.05). Compared with ISB patients, ST patients had significantly less diaphragmatic excursion at 3 h after block（P<0.05). 30 minutes after block, 8.7% patients in ISB group reached complete HDP and 52.2% patients reached partial HDP. At the same time, no complete HDP and 26.1% partial HDP were detected in ST group. 3 hours after block, patients in ST group had lower complete HDP rate (0.0% vs 17.4%) and lower partial HDP rate (39.1% vs 65.2%) than patients in ISB group. At 30 minutes and 3 h after block, the reduction of grip strength in ST group was significantly lower than that in ISB group (P<0.001). ST group had lower NRS than ISB group (P<0.05). The average block time in ISB group (8.3±1.97 )h was significantly lower than that in ST group (10.9±1.26)h (P<0.01). Conclusion Superior trunk block with 10 ml 0.25% ropivacaine is superior compared to interscalene brachial plexus block in occurrence of HDP, decrease of grip strength, postoperative pain and block duration.