To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.

Objective:To investigate the clinical efficacy of Full-endoscopic pars debridement, graft with autograft and recombinant human bone morphogenetic protein 2 (rhBMP-2), and percutaneous pedicle screw (PPS) fixation for the treatment of lumbar spondylolysis.Methods:A retrospective analysis was performed for the case data of 8 patients (7 males and 1 female) of lumbar spondylolysis treated with full-endoscopic pars bone graft with autograft and rhBMP-2 combined with PPS fixation in the fourth medical center of PLA general hospital. The mean age was 21.8±4.1 years (range, 16-29 years). All cases had mono-segmental bilateral pars defects, including 2 cases of L 4 and 6 cases of L 5. The visual analogue scale (VAS) and the Oswestry disability index (ODI) were recorded before and after surgery. MacNab score was used to evaluate the final clinical outcome of lumbar function at 1 year after the removal of internal fixation. Multi-planar reconstruction of CT scans was used to evaluate the bone healing at 6 and 12 months after the operation, and par condition at 1 year after the removal of internal fixation. Pfirrmann's grading system through MRI was used to grade disc degeneration in the fixed and adjacent discs respectively before the operation, before the removal of internal fixation, and 1 year after the removal of internal fixation. Results:All the operations were successfully completed. All patients were followed up for 24-30 months, with an average follow-up time of 27.75±3.11 months. Both VAS of back pain (1.63±0.74, 1.25±0.71、1.00±0.53) and ODI (10.25%±5.17%、6.33%±5.03%、4.86%±3.35%) at 6 and 12 months after the operation and 1 year after the removal of internal fixation were improved compared with those preoperatively (7.25±1.04 and 40.67%±9.67%), with significant differences ( P<0.05). The improvement rates of VAS and ODI at one year after pars repair were 83.31%±8.85% and 85.22%±9.60%, respectively. The improvement rates of VAS and ODI at one year after the removal of internal fixation were 85.96%±6.97% and 88.05%±7.25%, respectively. At the final follow-up, 7 patients had excellent results and 1 patient had good results according to the MacNab criteria. There were 3 patients bony healed in 6 months postoperatively and the remaining 5 patients bony healed in 12 months postoperatively. There was no pars re-rupture at the one-year follow-up after the removal of internal fixation. Disc degeneration increase one grade at the fixed disc in one patient before and after the removal of internal fixation than before pars repair surgery. Disc degeneration increase one grade at the adjacent disc in one patient before and after the removal of internal fixation than before pars repair surgery. There were no intraoperative or postoperative complications, such as nerve injury, cerebrospinal fluid leakage, incision exudation, infection, or breakdown of internal fixation device. Conclusions:Full-endoscopic pars bone debridement, graft with autograft and rhBMP-2, followed by PPS fixation is a safe and effective minimally invasive spine surgery for treating lumbar spondylolysis. It has the advantages of a high fusion rate, low incidence of complications, no pars re-rupture after the removal of internal fixation and no significantly increasing intervertebral disc degeneration in fixed and adjacent discs.

Objective:To investigate the clinical efficacy of Full-endoscopic pars debridement, graft with autograft and recombinant human bone morphogenetic protein 2 (rhBMP-2), and percutaneous pedicle screw (PPS) fixation for the treatment of lumbar spondylolysis.Methods:A retrospective analysis was performed for the case data of 8 patients (7 males and 1 female) of lumbar spondylolysis treated with full-endoscopic pars bone graft with autograft and rhBMP-2 combined with PPS fixation in the fourth medical center of PLA general hospital. The mean age was 21.8±4.1 years (range, 16-29 years). All cases had mono-segmental bilateral pars defects, including 2 cases of L 4 and 6 cases of L 5. The visual analogue scale (VAS) and the Oswestry disability index (ODI) were recorded before and after surgery. MacNab score was used to evaluate the final clinical outcome of lumbar function at 1 year after the removal of internal fixation. Multi-planar reconstruction of CT scans was used to evaluate the bone healing at 6 and 12 months after the operation, and par condition at 1 year after the removal of internal fixation. Pfirrmann's grading system through MRI was used to grade disc degeneration in the fixed and adjacent discs respectively before the operation, before the removal of internal fixation, and 1 year after the removal of internal fixation. Results:All the operations were successfully completed. All patients were followed up for 24-30 months, with an average follow-up time of 27.75±3.11 months. Both VAS of back pain (1.63±0.74, 1.25±0.71、1.00±0.53) and ODI (10.25%±5.17%、6.33%±5.03%、4.86%±3.35%) at 6 and 12 months after the operation and 1 year after the removal of internal fixation were improved compared with those preoperatively (7.25±1.04 and 40.67%±9.67%), with significant differences ( P<0.05). The improvement rates of VAS and ODI at one year after pars repair were 83.31%±8.85% and 85.22%±9.60%, respectively. The improvement rates of VAS and ODI at one year after the removal of internal fixation were 85.96%±6.97% and 88.05%±7.25%, respectively. At the final follow-up, 7 patients had excellent results and 1 patient had good results according to the MacNab criteria. There were 3 patients bony healed in 6 months postoperatively and the remaining 5 patients bony healed in 12 months postoperatively. There was no pars re-rupture at the one-year follow-up after the removal of internal fixation. Disc degeneration increase one grade at the fixed disc in one patient before and after the removal of internal fixation than before pars repair surgery. Disc degeneration increase one grade at the adjacent disc in one patient before and after the removal of internal fixation than before pars repair surgery. There were no intraoperative or postoperative complications, such as nerve injury, cerebrospinal fluid leakage, incision exudation, infection, or breakdown of internal fixation device. Conclusions:Full-endoscopic pars bone debridement, graft with autograft and rhBMP-2, followed by PPS fixation is a safe and effective minimally invasive spine surgery for treating lumbar spondylolysis. It has the advantages of a high fusion rate, low incidence of complications, no pars re-rupture after the removal of internal fixation and no significantly increasing intervertebral disc degeneration in fixed and adjacent discs.

An etiological analysis of a diarrhea outbreak attributed to C.perfringens was conducted.Anal swab and envi-ronmental smear samples were collected and subjected to fluorescence PCR detection of C.perfringens plc and cpe,as well as isolation and culture of C.perfringens before and after enrichment culture.The isolated colonies underwent fully automated bi-ochemical identification and time-of-flight mass spectrometry analysis.Whole genome sequencing of isolates identified as C.perfringens was performed to analyze the strain carrying virulence and resistance genes,and the genetic aggregation based on single nucleotide polymorphisms in the core genome for all isolates.The positivity rates for plc and cpe genes without bacterial enhancement were 46.15％(6/13)and 53.85％(7/13),respectively.The positivity rates for plc and cpe genes after 24 h anae-robic bacterial enhancement in BHI were 38.46％(5/13)and 53.85％(7/13).All ten isolated CP belonged to the F biotype,with virulence gene characteristics of plc+/cpb-/etx-/iA-/cpe+/cpb2+/netB-.The phylogenomic tree indicated that all ten case-patient isolates except P1 isolate(lineage 1)were closely related and clustered together in a single clade(lineage 2).Lineage 1 belonged to ST589 and carried the macrolide re-sistance gene erm(Q),whereas lineage 2 belonged to ST149 and carried the tetracycline resistance gene tetB(P).The outbreak was caused by type F C.perfringens,and most ca-ses were infected with a group of highly clonogenic cpe+col-onies.Whole genome sequencing technology can be applied to etiology analysis of C.perfringens outbreak events,and the enrichment culture and molecular screening methods for C.per-fringens based on anal swab samples should be further developed and applied.

OBJECTIVE To predict potential quality markers(Q-markers) in Yinhua Miyanling tablets based on fingerprinting and network pharmacology methods. METHODS HPLC fingerprints of 13 batches of Yinhua Miyanling tablets were established, and the similarity analysis was carried out using the "Chromatographic Fingerprint Evaluation System for Traditional Chinese Medicine" to identify the common peaks and attribute them. The fingerprints of Yinhua Miyanling tablets were investigated using chemometrics, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis in combination with SPSS 26.0 and SIMCA 14.1 software to identify the major signature components responsible for the differences. The network pharmacology was used to screen and analyze the targets and pathways of Yinhua Miyanling tablets, construct a "drug-component-target-pathway" network diagram, and predict the Q-Marker and core targets of Yinhua Miyanling tablets. RESULTS HPLC fingerprint of Yinhua Miyanling tablets was established, and 27 common peaks including chlorogenic acid, mangostin, wild baicalin, lignocerin and quercetin were identified. Chemical pattern recognition analysis screened five components as differential markers for Yinhua Miyanling tablets. Five active ingredients, 20 core targets and 20 key pathways were screened by network pharmacology, showing that all five active ingredients could be used as potential Q-Markers. CONCLUSION The method is stable, accurate and feasible for screening five chemical components as potential Q-Markers for Yinhua Miyanling tablets. It provides a reference for the overall control of the quality of Yinhua Miyanling tablets, and also lays the foundation for further research on the mechanism of action of Yinhua Miyanling tablets.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objectives:To study the technical notes and clinical outcomes of full-endoscopic interbody fusion via transforaminal approach for hard disc hemiations in thoracolumbar junction.Methods:14 patients with disc herniations involving 20 segments of hard disc hemiations in thoracolumbar junction treated with full-en-doscopic interbody fusion via transforaminal approach between January 2018 and September 2021 were includ-ed in the study.There were 11 males and 3 females with an average age of 43.3±12.6 years;3-segment dis-ease in 2 cases,2-segment disease in 2 cases,and single segment disease in 10 cases.The hard compres-sion were classified as:3 cases of calcified disc hemiation,6 cases of osteophyte protrusion of the posterior edge of the adjacent vertebral body of the diseased disc,3 cases of disc hemiations with atypical Scheuer-mann disease and 2 cases of disc herniation with epiphyseal separation.All patients had symptoms of myelopathy or cauda equina compromise before operation,and 6 of them had radiculopathy.Via transforaminal approach under local anesthesia,full-endoscopic interbody fusion and discectomy were performed firstly,fol lowed with percutaneous pedicle screw system placement and fixation under general anesthesia.Postoperative imaging changes,pain symptoms and recovery of neurological function at 1 week,3 months,6 months and 1 year after operation were observed.Back pain and radicular pain were scored with visual analogue scale(VAS),neurological function was assessed with Nurick score and modified Japanese Orthopaedic Association(mJOA)score,and thoracic spine function was assessed with Oswestry disability index(ODI).Results:All operations were successfully completed,and no intraoperative conversion of surgical methods occurred.Postoperative tho-racolumbar junction MRI and CT examinations of all patients showed that the spinal cord or cauda equina was sufficiently decompressed without any residual compression.At 1 year follow-up,all surgical segments were fused.Back pain and radicular pain were all relieved significantly in all the patients,and neurological function was significantly restored.The Nurick score,mJOA score and ODI all improved compared with the preoperative values(P＜0.01),and the postoperative 1 year values all improved significantly compared with the values at postoperative 1 week,3 months and 6 months(P＜0.01).The average recovery rate of mJOA was 72.5％,with 7 cases excellent,5 cases good and 2 cases fair.Dural tear occurred in 2 cases during opera-tion,but no cerebrospinal fluid leakage and pseudomeningocele occurred during follow-up.No other surgical complications occurred.Conclusions:Full-endoscopic interbody fusion and resection of herniated hard disc vi-a transforaminal approach under local anesthesia followed with percutaneous pedicle screw system fixation un-der general anesthesia are safe and effective minimally invasive spine surgery for the treatment of hard disc herniation located in the thoracolumbar junction.

Objective:To observe the role of complement C3 in the process of renal interstitial fibrosis.Methods:Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient (C3KO) mice and age-matched C57BL/6 wild type (WT) mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in WT group (WTcontrol) ( n=6), UUO operation in WT group (WTuuo) ( n=6), sham operation in C3-deficient group (C3KOcontrol) ( n=6), and UUO operation in C3-deficient group (C3KOuuo) ( n=6). Tubular interstitial fibrosis was observed by both HE staining and Masson staining. The expression of C3, trypsin (tryptase), angiotensinⅡ (AngⅡ), transforming growth factor β1 (TGF-β1), and matrix metalloproteinase-9 (MMP-9) was detected by immunohistochemical staining. Chymase level were assessed by immunofluorescence staining. The levels of AngⅡ and C3 cleavage fragments C3a and MMP-9 were determined by enzyme-linked immunosorbent assay. The change in renin mRNA was determined by real-time PCR. The changes of chymase, renin, and TGF-β1 were detected by Western blotting. Results:Compared with the WTcontrol group mice, the WTuuo group mice showed significant renal tubular injury, renal interstitial fibrosis, increased infiltration of mast cells, and significantly increased expression of C3, C3a, chymase, renin, AngⅡ, TGF-β1, and MMP-9 in the renal tissue (all P<0.05). Compared with the WTuuo group mice, the renal tubular injury and renal interstitial fibrosis in the C3KOuuo group mice were significantly reduced, and C3 and C3a were not detected in renal tissue. Mast cells infiltration was reduced, and the expression of chymase, renin, AngⅡ, TGF-β1, and MMP-9 was weakened (all P<0.05). Conclusion:C3/C3a can participate in the recruitment and activation of mast cells to release chymase in kidney interstitial fibrosis, and promote the expression of renin, AngⅡ, TGF-β1, MMP 9 and other substances, thus aggravating kidney injury.

Objective:To observe the role of complement C3 in the process of renal interstitial fibrosis.Methods:Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient (C3KO) mice and age-matched C57BL/6 wild type (WT) mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in WT group (WTcontrol) ( n=6), UUO operation in WT group (WTuuo) ( n=6), sham operation in C3-deficient group (C3KOcontrol) ( n=6), and UUO operation in C3-deficient group (C3KOuuo) ( n=6). Tubular interstitial fibrosis was observed by both HE staining and Masson staining. The expression of C3, trypsin (tryptase), angiotensinⅡ (AngⅡ), transforming growth factor β1 (TGF-β1), and matrix metalloproteinase-9 (MMP-9) was detected by immunohistochemical staining. Chymase level were assessed by immunofluorescence staining. The levels of AngⅡ and C3 cleavage fragments C3a and MMP-9 were determined by enzyme-linked immunosorbent assay. The change in renin mRNA was determined by real-time PCR. The changes of chymase, renin, and TGF-β1 were detected by Western blotting. Results:Compared with the WTcontrol group mice, the WTuuo group mice showed significant renal tubular injury, renal interstitial fibrosis, increased infiltration of mast cells, and significantly increased expression of C3, C3a, chymase, renin, AngⅡ, TGF-β1, and MMP-9 in the renal tissue (all P<0.05). Compared with the WTuuo group mice, the renal tubular injury and renal interstitial fibrosis in the C3KOuuo group mice were significantly reduced, and C3 and C3a were not detected in renal tissue. Mast cells infiltration was reduced, and the expression of chymase, renin, AngⅡ, TGF-β1, and MMP-9 was weakened (all P<0.05). Conclusion:C3/C3a can participate in the recruitment and activation of mast cells to release chymase in kidney interstitial fibrosis, and promote the expression of renin, AngⅡ, TGF-β1, MMP 9 and other substances, thus aggravating kidney injury.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.