Nardostachys jatamansi and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.

CONTEXT: Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. OBJECTIVE: To explore the synergistic effect of NJ combined with levodopa against PD. MATERIALS AND METHODS: The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. RESULTS: Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. DISCUSSION AND CONCLUSIONS: NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.

Analysis of Prevention and Treatment of Anastomotic Leakage after Sphincter-Preserving Surgery for Middle- and Low-Grade Rectal Cancer under Laparoscopy.

Background: Anastomotic leakage is one of the most serious complications that can occur after laparoscopic-assistedsphincter-preserving surgery for middle- and low-grade rectal cancer. Objectives: To explore the cause, prevention, and treatment of anastomotic leakage after sphincter-preserving surgery for middle- and low-grade rectal cancer under laparoscopy. Methods: The clinical data from patients with mid- and low-grade rectal cancer who underwent laparoscopic-assistedanus-preserving surgery in the anorectal surgery department of our hospital have been analyzed. Patients with a definite diagnosis, indications for laparoscopic surgery, and sphincter-preserving surgery were included in the analysis, and patients with a protective loop ileostomy and laparotomy were excluded. Results: Among the 126 patients with middle- and low-grade rectal cancer undergoing sphincter-preserving surgery under laparoscopy. There were 75 male patients and 51 female patients, ranging in age from 37 to 89 years old, with an average age of 60.2 ± 6.7. The distance from the lower edge of the rectal tumor to the anal edge was ≤10 cm. 6 developed anastomotic leakage after the operation (leakage rate of 4.7%). Moreover, turbid purulent fluid was drained from the abdominal drainage tube in three patients on the third and fourth days after the operation, and the abdominal drainage tube drained serous drainage in three more patients on the fifth and sixth days, with signs of peritonitis appearing locally. All patients received continuous flushing and negative pressure drainage with a self-made double cannula and symptomatic treatment, and all were cured and discharged. Conclusion: Many factors can cause anastomotic leakage after this operation, and adequate perioperative preparation, meticulous operation during surgery, and careful postoperative management are key factors in preventing it.

[Effects of Nardostachys jatamansi on gut microbiota of rats with Parkinson's disease].

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1ß, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.

[Spectrum-effect relationship of hemostatic effects of Notoginseng Radix et Rhizoma with different commodity specifications].

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.

Quantum-limited timing jitter characterization of mode-locked lasers by asynchronous optical sampling.

We demonstrate a novel time domain timing jitter characterization method for ultra-low noise mode-locked lasers. An asynchronous optical sampling (ASOPS) technique is employed, allowing timing jitter statistics on a magnified timescale. As a result, sub femtosecond period jitter of an optical pulse train can be readily accessible to slow detectors and electronics (~100 MHz). The concept is applied to determine the quantum-limited timing jitter for a passively mode-locked Er-fiber laser. Period jitter histogram is acquired following an eye diagram analysis routinely used in electronics. The identified diffusion constant for pulse timing agrees well with analytical solution of perturbed master equation.

Clinical profiles and molecular genetic analyses of 98 Chinese children with short statures.

Background: Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is limited genetic research on exome sequencing for short stature, and more large-scale studies are necessary for further exploration. Methods: The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ -2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures. Results: The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome. Conclusion: WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.

Effects of repeated and continuous dry heat treatments on the physicochemical, structural, and in vitro digestion properties of chickpea starch.

The study investigated the impacts of repeated (RDH) and continuous dry heat (CDH) treatments on the physicochemical, structural, and in vitro digestion properties of chickpea starch. The results of SEM and CLSM showed that more fissures and holes appeared on the surface of granules as the treated time of CDH and the circles of RDH increased, both of which made the starch sample much easier to break down by digestive enzymes. Moreover, the fissures and holes of starch granules treated by CDH were more obvious than those of RDH. The XRD and FT-IR results suggested that the crystal type remained C-type, and the relative crystallinity and R1047/1022 of the chickpea starch decreased after dry heat treatments. In addition, a marked decline in the pasting viscosity and gelatinization temperature of chickpea starches was found with dry heat treatments. Moreover, the increased enzyme accessibility of starch was fitted as suggested by the increased RDS content and digestion rate. This study provided basic data for the rational design of chickpea starch-based foods with nutritional functions.

The m7G-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumour Immune Infiltration in Colon Cancer.

With high morbidity and mortality, colon cancer (CC) is considered as one of the most often diagnosed cancers around the world. M7G-related lncRNA may provide a regulatory function in the formation of CC, but the principle of regulation is still unclear. The purpose of this research was to establish a novel signature that may be used to predict survival and tumour immunity in CC patients. Data about CC in TCGA was collected for analysis, coexpression analysis and univariate Cox analysis were used to screen prognostic m7G-related lncRNAs. A consensus clustering analysis based on prognostic m7G-related lncRNAs was applied, and a prognosis model based on least absolute shrinkage and selection operator (LASSO) regression analysis was established. Independent prognostic analysis, nomogram, PCA, clinicopathological correlation analysis, TMB, survival analysis, immune correlation analysis, qRT-PCR and clinical therapeutic compound prediction were also applied. 90 prognostic m7G-related lncRNAs were found, GO and KEGG analysis showed that prognostic m7G-related lncRNAs were mainly related to cell transcription and translation. The results of the consensus clustering analysis revealed substantial disparities in survival prognosis and tumour immune infiltration between two clusters. We built a risk model with 21 signature m7G-related lncRNAs, patients in the high-risk group had a considerably poorer prognosis than those in the low-risk group. Independent prognostic analysis confirmed that patients' prognosis was linked to their tumour stage and risk score. PCA, subgroups with distinct clinicopathological characteristics were studied for survival, multi-index ROC curve, c-index curve, the survival analysis of TMB, and model comparison tested the reliability of risk model. A tumour immunoassay revealed a substantial difference in immune infiltration between high-risk and low-risk individuals. Five chemicals were eliminated, and qRT-PCR indicated that the four lncRNAs were expressed differently. Overall, m7G-related lncRNA is closely related to colon cancer and the 21 signature lncRNAs risk model can efficiently evaluate the prognosis of CC patients, which has a possible positive consequence for the future diagnosis and therapy of CC.

Dose Optimization of Anxiolytic Compounds Group in Valeriana jatamansi Jones and Mechanism Exploration by Integrating Network Pharmacology and Metabolomics Analysis.

Anxiety disorder impacts the quality of life of the patients. The 95% ethanol extract of rhizomes and roots of Valeriana jatamansi Jones (Zhi zhu xiang, ZZX) has previously been shown to be effective for the treatment of anxiety disorder. In this study, the dose ratio of each component of the anxiolytic compounds group (ACG) in a 95% ethanol extract of ZZX was optimized by a uniform design experiment and mathematical modeling. The anxiolytic effect of ACG was verified by behavioral experiments and biochemical index measurement. Network pharmacology was used to determine potential action targets, as well as predict biological processes and signaling pathways, which were then verified by molecular docking analysis. Metabolomics was then used to screen and analyze metabolites in the rat hippocampus before and after the administration of ZZX-ACG. Finally, the results of metabolomics and network pharmacology were integrated to clarify the anti-anxiety mechanism of the ACG. The optimal dose ratio of ACG in 95% ethanol extract of ZZX was obtained, and our results suggest that ACG may regulate ALB, AKT1, PTGS2, CYP3A4, ESR1, CASP3, CYP2B6, EGFR, SRC, MMP9, IGF1, and MAPK8, as well as the prolactin signaling pathway, estrogen signaling pathway, and arachidonic acid metabolism pathway, thus affecting the brain neurotransmitters and HPA axis hormone levels to play an anxiolytic role, directly or indirectly.

Clinical study of use of large C suture in procedure for prolapse and hemorrhoids for treatment of mixed hemorrhoids.

OBJECTIVE: To investigate the clinical use of a large C suture in the procedure for prolapse and hemorrhoids (PPH) for treatment of mixed hemorrhoids. METHODS: Patients with mixed hemorrhoids (grade III or IV) who underwent treatment with a large C suture during PPH in the Affiliated Hospital (Group) of Putian University from 1 April 2018 to 31 March 2019 were enrolled in this retrospective study. The incidences of anastomotic stenosis and anastomotic hemorrhage after the operation were observed. RESULTS: The study population comprised 126 patients (46 men and 80 women) ranging in age from 30 to 78 years (mean, 46.1 ± 2.5 years). Of these patients, 60 had circular mixed hemorrhoids, 36 had grade III circular internal hemorrhoids, and 30 had grade IV circular internal hemorrhoids. The onset time among all patients ranged from 0.5 to 25 years. All patients underwent 6 months of postoperative follow-up. None of the patients with mixed hemorrhoids developed anastomotic stenosis, although two patients developed secondary anastomotic bleeding. CONCLUSION: Placement of a large C suture during PPH is a reliable technique for treatment of mixed hemorrhoids. It is simple, effective, and applicable and can be helpful for a large number of patients in primary hospitals.

Short-term clinical and oncological outcomes after single-incision plus one-port laparoscopic surgery for rectosigmoid cancer: a retrospective clinical analysis of 30 cases.

OBJECTIVE: To evaluate the safety and feasibility of single-incision laparoscopic surgery+1 (SILS+1) radical resection of sigmoid and upper rectal cancer. METHODS: The clinical data of 30 consecutive patients with sigmoid and upper rectal cancer who underwent SILS+1 radical resection between October 2018 and January 2020 in our hospital were retrospectively analyzed. An initial 5-cm periumbilical transverse incision was made. Then, a multiport device was placed in the umbilical incision. Two 10-mm ports were used for laparoscope insertion, and the other two ports were used for laparoscope device insertion. A 12-mm trocar was placed in the right lower abdominal quadrant under laparoscopic view and served as the surgeon's dominant operating channel. RESULTS: All operations were performed successfully without conversion to conventional laparoscopic surgery or open operation. Three patients developed postoperative complications: one patient developed ileus, one developed postoperative bleeding, and one developed wound infection. There were no perioperative deaths. CONCLUSIONS: The safety and feasibility of SILS+1 radical resection of sigmoid and upper rectal cancer was established by experienced surgeons in our study. However, further studies are needed to demonstrate the advantages of this procedure compared with the benefits of conventional laparoscopic surgery.