Objective To study the effect of reactive oxygen species(ROS)/p38 MAPK cascade reaction on the formation of kidney stones(KS)in rats and explore the mechanism.Methods Fifty SD rats were randomly divided into control group(normal feeding),N-acetylcysteine(NAC)group(intraperitoneally injected 200 mg/kg NAC),KS group(constructed calcium oxalate KS model),KS+NAC group(constructed calcium oxalate KS model,intraperitoneally injected 200 mg/kg NAC),KS+NAC+tunicamycin(TM)group(constructed calcium oxalate KS model,intraperitoneally injected 200 mg/kg NAC and 1 mg/kg TM),with 10 rats in each group.After 4 weeks of administration,24 hours urine volume and oxalic acid(Ox)of each group were measured,serum creatinine(Cr),urea nitrogen(BUN)and uric acid(UA)levels were detected by automatic biochemical analyzer.HE staining and Von Kossa staining were used to observe the histopathological changes and crystal deposition of the kidney.TUN EL staining was used to detect apoptosis of renal tissue cells.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in renal tissue were measured by the kit.DHE fluorescent probes detected the levels of reactive oxygen species(ROS)in kidney tissue.Immunohistochemical staining was used to detect the expressions of microtubule-associated protein 1 light chain 3 B(LC3B)and glucose regulatory protein 78(GRP78)in renal tissue,and the protein expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78,CCAAT/enhancer binding protein homologous protein(CHOP)in renal tissue was determined by Western blotting.Results Compared with the KS group,Ox in KS+NAC group decreased(P＜0.05),BUN,Cr and UA levels decreased(P＜0.05),renal tubule dilatation and calcium oxalate crystallization decreased,TUNEL positive cell rate decreased(P＜0.05),SOD activity increased and MDA content decreased(P＜0.05),ROS levels decreased(P＜0.05),LC3B and GRP78 positive staining levels decreased(P＜0.05),the relative protein expressions of p-p38 MAPK/p38 MAPK,LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78 and CHOP were down-regulated(P＜0.05).Compared with the KS+NAC group,Ox in KS+NAC+TM group increased(P＜0.05),BUN,Cr and UA levels also increased(P＜0.05),renal tubule dilated significantly,calcium oxalate crystals increased,TUNEL positive cell rate increased(P＜0.05),SOD activity decreased and MDA content increased(P＜0.05),ROS levels increased(P＜0.05),LC3B and GRP78 positive staining levels increased(P＜0.05),the relative protein expressions of p-p38 MAPK/p38 MAPK,LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78 and CHOP were also up-regulated(P＜0.05).Conclusion ROS/p38 MAPK cascade is involved in promoting KS formation in rats,which is related to the activation of endoplasmic reticulum stress-mediated autophagy pathway.

Objective To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS)and the difference of physiological curvature between different types of scoliosis.Methods A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021.The patients were divided into normal group and scoliosis group.The normal group was composed of 179 patients,79 males and 100 females,aged 10 to 18 years old with an average of(12.84±2.10)years old,with cobb agle less than 10 degrees.The scol-iosis group was composed of 126 patients,33 males and 93 females,aged 10 to 18 years old with an average of(13.92±2.20)years old.The gender,age,Risser sign,thoracic kyphosis(TK)and lumbar lordosis(LL)in 2 groups were compared,and the TK and LL were also compared between different genders,different degrees of scoliosis and different segments of scoliosis.Re-sults The female ratio(P=0.001)and age(P＜0.001)in scoliosis group were higher than them in normal group;the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038).TK was significantly smaller in scoliosis group than in normal group(P＜0.001),but there was no significant difference in LL between the 2 groups(P=0.147).There were no significant difference in TK and LL between male and female.The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P＜0.05),but there was no significant difference in LL between mild and moderate patients(P＞0.05).The TK and LL in different segments scoliosis were not found significant difference.Conclusion The physiological curvature of thoracic and lumbar spine is independent of gender.The thoracic physiological curvature becomes smaller in AIS patients,but lumbar curvature remains unchanged.The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients,but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent.The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative an-terior spinal overgrowth,and the specific detailed mechanism needs to be further studied.

OBJECTIVE: This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats. METHODS: The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA. RESULTS: APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05). CONCLUSION EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.
Rats ; Animals ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Electroacupuncture ; Pain, Postoperative ; Interferons

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.
Male ; Humans ; Prostatic Hyperplasia/complications* ; Quality of Life ; Transurethral Resection of Prostate/adverse effects* ; Treatment Outcome ; Enhanced Recovery After Surgery

OBJECTIVE: Dexmedetomidine (DEX), the most specific α ₂-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. METHODS: We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O ₂) and hypoxic (1% O ₂) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. RESULTS: The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). CONCLUSION We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α ₂-adrenergic receptor mediation might be the critical mechanisms.
Animals ; Humans ; Mice ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Carcinoma, Hepatocellular ; Cardiovascular Physiological Phenomena ; Dexmedetomidine/pharmacology* ; Hypoxia ; Liver Neoplasms/drug therapy* ; Oxygen ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/genetics* ; Receptors, Adrenergic, alpha-2/metabolism*

Objective:To discuss the strategies of distal embolic filter protection(DEFP) during excimer laser ablation (ELA) or percutaneous mechanical thrombectomy (PMT) in treatment of peripheral artery disease.Methods:Clinical data of 29 patients undergoing ELA or PMT under the DEFP from Oct 2019 to Aug 2021 were retrospectively collected to analyze the strategies of DEFP and high-risk factors of capturing clinically significant macrodebris.Results:There were 21 males and 8 females, aged (70.3±11.0) years with 32 lesions (29 limbs) including 5 in-stent restenosis (ISR), 10 thrombosis and 17 chronic total occlusion (CTO). The technical success rate of DEFP device release and recovery was 100%. The overall debris capture rate was 77.3% and the macrodebris capture rate was 36.4%. Even with DEFP the distal embolization (DE) incidence was 3.4%. When ELA for CTO with severe calcification or long-segment ISR lesions, the capture rate of macrodebris was as high as 60.0%, and the former was significantly higher than ELA for CTO without high calcification lesions ( P<0.05). Conclusion:ELA or PMT under the DEFP in treatment of peripheral artery disease appears to be of great significance in preventing DE.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.