Objective To investigate the effect of dioscin on uric acid(UA)-induced oxidative stress injury of human renal tubular epithelial cells(HK-2)and its molecular mechanism.Methods HK-2 cells were cultured and divided into four groups:blank group(normal group),model group(uric acid-stimulation modeling),condition control group(UA+DMSO)and dioscin group(UA+dioscin).Oxidative stress injury model was induced by UA in HK-2 cells.Cells viability was detected by CCK-8.ROS level was detected by flow cytometry.Real-time PCR was used to detect the expressions of glycogen synthase kinase 3β(GSK3β),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)at mRNA level,and Western Blot was used to detect the expressions of phosphorylated glycogen synthesis kinase 3β(p-GSK3β),GSK3β,Nrf2 and HO-1 at protein level.Results After stimulation by UA,HK-2 cells viability was obviously decreased,and ROS level was significantly increased(all P＜0.001).When treated with dioscin,HK-2 cells viability was obviously increased,and the ROS level of HK-2 cells was significantly decreased(all P＜0.001).The expressions of Nrf2 and HO-1 decreased at the protein and mRNA levels after stimulation with UA.But the expressions of Nrf2 and HO-1 significantly increased after treated with dioscin(all P＜0.001).Compared with the blank group,the p-GSK3β/GSK3β ratio in the model group decreased significantly at the protein level,but the p-GSK3β/GSK3β ratio increased after treated with dioscin(all P＜0.001).Conclusion Dioscin can alleviate UA-induced oxidative stress injury in HK-2 cells.The mechanism might be that dioscin can promote phosphorylation of GSK3β,and activate Nrf2/HO-1 pathway.

BACKGROUND:Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress.Resveratrol has anti-inflammatory and anti-oxidative stress biological effects,and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE:To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into control group,model group,low-dose resveratrol group,and high-dose resveratrol group,with 10 rats in each group.Knee osteoarthritis models were established in the model group,low-dose resveratrol group,and high-dose resveratrol group.A mixture of 4%papain solution and 0.3 mol/L cysteine solution(1:1 for 0.5 hours;20 μL)was injected at 1,4,and 7 days after modeling.Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling,while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity.After 28 days of treatment,the maximum knee joint activity was measured;the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA;the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining;the degree of arthritic lesions was analyzed using the Mankin histological score;and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION:Compared with the model group,the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups,and were significantly higher in the high-dose group than the low-dose group(P<0.05).Compared with the model group,the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups.The level of malondialdehyde significantly decreased in both resveratrol groups,and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group(P<0.05).Compared with the model group,the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β,interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats,and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group(P<0.05).Compared with the model group,the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups,and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group(P<0.05).Compared with the model group,the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups,while the level of acetylated FOXO1 significantly decreased(P<0.05).The magnitude of changes was significantly better in the high-dose group than the low-dose group.To conclude,resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner,possibly through the SIRT1/FOXO1 pathway.

Objective To explore the effectiveness and safety of guiding painless gastroscopic entry with plica aryepiglottica movement as the mark.Methods A total of 200 patients with elective painless gas-troscopic examination from January 2022 to August 2022 were selected,92 males and 108 female,aged 18-60 years old,BMI 18-30 kg/m2 and ASA grade Ⅰ-Ⅲ.The patients were divided into the two groups:the con-trol group (group C) and observation group (group O) by adopting the random number table method,100 ca-ses in each group.The disappearance of eyelash reflex in the group C served as the entry timing of gastrosco-py,while the plica aryepiglottica non-movement under the gastroscopic view in the group O served as the en-try timing of gastroscopy.The bispectral index (BIS) value during gastroscopic operation persistently main-tained 40-60.The main observation indicators were the adverse reactions caused by gastroscopic operation (body movement reactions,bucking,hiccup,laryngeal spasm,etc.),and the secondary observation indicators were:general data of the two groups,SpO2,HR,SBP and DBP values after entering the room (T0),at the en-try time of gastroscopy (T1),3 min after gastroscopic entry (T2),6 min after gastroscopic entry (T3) and at the time of gastroscopic retraction (T4),and the time of medication to gastroscopy,gastroscopic operation time and intraoperative medication supplementation.Results A total of 192 cases were ultimately included,99 cases in the group C and 93 cases in the group O.There was no statistically significant difference in general da-ta between the two groups (P>0.05);compared with the group C,the use amount of cyclophosphamide dur-ing anesthesia induction in the group O was increased (P<0.05).Compared with the group C,the incidence rates of body movement reaction,bucking,hiccup and total adverse reactions in the group O were decreased (P<0.05);SpO2,HR,SBP and DBP at different time points had no statistically significant differences be-tween the two groups (P>0.05).Conclusion Using the glottic movement as the marker to guide the pain-less gastroscopy entry is effective and safe,and could reduce the adverse reactions such as body movement re-action,bucking and hiccup caused by gastroscopic entry.Observing the plica aryepiglottica movement in the gastrocopic entry operation is simple and easy to perform,which could serve an objective gastroscopic entry timing mark and is worth promoting and using in clinic.

Postoperative cognitive dysfunction(POCD)is a common complication in the periopera-tive period,posing a significant threat to patients'brain health and rapid recovery.However,the specific pathogenesis remains unclear,resulting in a lack of effective prevention and treatment methods.The theoret-ical research on cognitive function diseases in traditional Chinese medicine provides valuable insights for comprehensive POCD prevention and treatment.In clinical practice,emphasis is placed on nurturing the"spirit"before surgery and regulating it afterwards while also harmonizing the heart,liver,kidney,and oth-er organs.This approach has shown promising results.Guided by traditional Chinese medicine theory,clini-cal practice has significantly enriched our understanding of POCD prevention and treatment methods while opening up new avenues for future treatments.This article reviews recent advances in theoretical research and clinical practices of traditional Chinese medicine regarding POCD with the aim of exploring more effec-tive ideas and approaches for its prevention and treatment.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Polyurethane (PUR) plastics is widely used because of its unique physical and chemical properties. However, unreasonable disposal of the vast amount of used PUR plastics has caused serious environmental pollution. The efficient degradation and utilization of used PUR plastics by means of microorganisms has become one of the current research hotspots, and efficient PUR degrading microbes are the key to the biological treatment of PUR plastics. In this study, an Impranil DLN-degrading bacteria G-11 was isolated from used PUR plastic samples collected from landfill, and its PUR-degrading characteristics were studied. Strain G-11 was identified as Amycolatopsis sp. through 16S rRNA gene sequence alignment. PUR degradation experiment showed that the weight loss rate of the commercial PUR plastics upon treatment of strain G-11 was 4.67%. Scanning electron microscope (SEM) showed that the surface structure of G-11-treated PUR plastics was destroyed with an eroded morphology. Contact angle and thermogravimetry analysis (TGA) showed that the hydrophilicity of PUR plastics increased along with decreased thermal stability upon treatment by strain G-11, which were consistent with the weight loss and morphological observation. These results indicated that strain G-11 isolated from landfill has potential application in biodegradation of waste PUR plastics.
Plastics/metabolism* ; Polyurethanes/chemistry* ; RNA, Ribosomal, 16S ; Bacteria/genetics* ; Biodegradation, Environmental

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

OBJECTIVE: To analyze the early effectiveness of unilateral biportal endoscopy (UBE) laminectomy in the treatment of two-level lumbar spinal stenosis (LSS). METHODS: The clinical data of 98 patients with two-level LSS treated with UBE between September 2020 and December 2021 were retrospectively analyzed. There were 53 males and 45 females with an average age of 59.9 years (range, 32-79 years). Among them, there were 56 cases of mixed spinal stenosis, 23 cases of central spinal canal stenosis, and 19 cases of nerve root canal stenosis. The duration of symptoms was 1.5- 10 years, with an average of 5.4 years. The operative segments were L _{2, 3} and L _{3, 4} in 2 cases, L _{3, 4} and L _{4, 5} in 29 cases, L _{4, 5} and L _5, S ₁ in 67 cases. All patients had different degrees of low back pain, among of which 76 cases were with unilateral lower extremity symptoms and 22 cases were with bilateral lower extremity symptoms. There were 29 cases of bilateral decompression in both segments, 63 cases of unilateral decompression in both segments, and 6 cases of unilateral decompression and bilateral decompression of each segment. The operation time, intraoperative blood loss, total incision length, hospitalization stay, ambulation time, and related complications were recorded. Visual analogue scale (VAS) score was used to assess the low back and leg pain before operation and at 3 days, 3 months after operation, and at last follow-up. The Oswestry disability index (ODI) was used to evaluate the functional recovery of lumbar spine before operation and at 3 months and last follow-up after operation. Modified MacNab criteria was used to evaluate clinical outcomes at last follow-up. Imaging examinations were performed before and after operation to measure the preservation rate of articular process, modified Pfirrmann scale, disc height (DH), lumbar lordosis angle (LLA), and cross-sectional area of the canal (CAC), and the CAC improvement rate was calculated. RESULTS: All patients underwent surgery successfully. The operation time was (106.7±25.1) minutes, the intraoperative blood loss was (67.7±14.2) mL, and the total incision length was (3.2±0.4) cm. The hospitalization stay was 8 (7, 9) days, and the ambulation time was 3 (3, 4) days. All the wounds healed by first intention. Dural tear occurred in 1 case during operation, and mild headache occurred in 1 case after operation. All patients were followed up 13-28 months with an average of 19.3 months, and there was no recurrence or reoperation during the follow-up. At last follow-up, the preservation rate of articular process was 84.7%±7.3%. The modified Pfirrmann scale and DH were significantly different from those before operation ( P<0.05), while the LLA was not significantly different from that before operation ( P=0.050). The CAC significantly improved ( P<0.05), and the CAC improvement rate was 108.1%±17.8%. The VAS scores of low back pain and leg pain and ODI at each time point after operation significantly improved when compared with those before operation, and the differences between each time points were significant ( P<0.05). According to the modified MacNab criteria, 63 cases were excellent, 25 cases were good, and 10 cases were fair, with an excellent and good rate of 89.8%. CONCLUSION UBE laminectomy is a safe and effective technique with little trauma and fast recovery for two-level LSS and the early effectiveness is satisfactory.
Male ; Female ; Humans ; Middle Aged ; Laminectomy ; Spinal Stenosis/surgery* ; Constriction, Pathologic/surgery* ; Low Back Pain ; Retrospective Studies ; Blood Loss, Surgical ; Endoscopy ; Lumbar Vertebrae/surgery* ; Spinal Fusion/methods* ; Decompression, Surgical ; Surgical Wound/surgery* ; Treatment Outcome

Objective To evaluate the effect of acupuncture(manual acupuncture,electroacu-puncture)on prevention and treatment of nausea and vomiting after general anesthesia.Methods By searching CNKI,VIP,China Biomedical Literature Database,Wanfang Medical,Embase,PubMed,Co-chrane Clinical Trial Registry,randomized controlled trial(RCT)on acupuncture combined with antiemetics for the prevention and treatment of nausea and vomiting after general anesthesia were performed.The retrieval period was from the establishment of the database to September 2022.RevMan 5.3 was used for statistical analysis.Results Fifteen studies involving 1 493 patients were included.There were 741 patients in the antiemetic group and 752 patients in the acupuncture combined antiemetic group.The incidence of postoperative nausea in the acupuncture combined with antiemetics group was significantly lower than that in the simple antiemetics group(OR=0.43,95％CI 0.34-0.54,P＜0.001).The incidence of postopera-tive vomiting in the acupuncture combined with antiemetics group was significantly lower than that in the simple antiemetics group(OR=0.55,95％CI 0.45-0.66,P＜0.001).Conclusion The incidence of postoperative nausea and vomiting was lower in patients treated with acupuncture(manual acupuncture,electroacupuncture)combined with antiemetics than with antiemetics alone.