AIM To study the chemical constituents from Fomes officinalis(Vill.ex Fr.)Ames and their anti-inflammatory activities.METHODS The 95％ethanol extract from F.officinalis was isolated and purified by silica gel,Sephadex LH-20,HW-40C,MCI and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as asperginine A(1),laricinolic acid(2),methoxylaricinolic acid(3),fomeffic acid(4),19-acetoxy-13S-hydroxylabda-8(17),14-diene(5),bisbenzopyran(6),lariciresinol acetate(7),fomitopsin G(8),fomitopsin H(9),demalonyl fomitopsin H(10),fomlactone A(11),fomlactone B(12),fomefficinol A(13),fomefficinol B(14),laetiporins A(15),laetiporins B(16),dehydrosulphurenic acid(17),dehydroeburicoic acid(18),3-keto-dehydrosulfurenic acid(19),eburicoic acid(20).The IC50 values of compounds 7,13,20 were(4.00±1.02),(3.29±0.62),(3.22±0.94)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,3,6,15,16 are isolated from this plant for the first time.Compounds 7,13,20 have strong anti-inflammatory activities.

AIM To study the chemical constituents from Fomes officinalis(Vill.ex Fr.)Ames and their anti-inflammatory activities.METHODS The 95％ethanol extract from F.officinalis was isolated and purified by silica gel,Sephadex LH-20,HW-40C,MCI and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as asperginine A(1),laricinolic acid(2),methoxylaricinolic acid(3),fomeffic acid(4),19-acetoxy-13S-hydroxylabda-8(17),14-diene(5),bisbenzopyran(6),lariciresinol acetate(7),fomitopsin G(8),fomitopsin H(9),demalonyl fomitopsin H(10),fomlactone A(11),fomlactone B(12),fomefficinol A(13),fomefficinol B(14),laetiporins A(15),laetiporins B(16),dehydrosulphurenic acid(17),dehydroeburicoic acid(18),3-keto-dehydrosulfurenic acid(19),eburicoic acid(20).The IC50 values of compounds 7,13,20 were(4.00±1.02),(3.29±0.62),(3.22±0.94)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,3,6,15,16 are isolated from this plant for the first time.Compounds 7,13,20 have strong anti-inflammatory activities.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Objective:Exploring the efficacy of indocyanine green（ICG）near-infrared fluorescence（NIRF）imaging technology in robotic-assisted laparoscopic partial nephrectomy for children with duplicated kidneys.Methods:A retrospective analysis was conducted on the medical records of 7 children with duplicated kidneys admitted to Guizhou Provincial People's Hospital from December 2023 to September 2024，including 3 males and 4 females. The patients with a median age of 36（2，132）months. All cases of duplicated kidneys were located at the renal pole，with 5 on the left side and 2 on the right side. All 7 patients had a history of worsening hydronephrosis，with 4 having a history of urinary tract infection and 1 accompanied by urinary incontinence（urine leakage outside the normal voiding period）. Preoperative diagnosis was confirmed via enhanced CT of the urinary tract，diuretic renal dynamic imaging（SPECT），and voiding cystourethrography. One case had an ectopic ureteral opening. One case had recurrent urinary tract infections following ureteral cyst fenestration surgery，and five cases had terminal ureteral obstruction. All seven cases showed that the functional capacity of the duplicated upper kidney was <10%. All 7 cases underwent robot-assisted laparoscopic repeated nephrectomy of the upper kidney using ICG-NIRF technology. Intraoperative ICG fluorescence imaging was performed in three stages：a catheter was inserted through the lower kidney ureter，and after the first injection of ICG，green fluorescence was observed in the lower kidney ureter. Under fluorescence guidance，the upper and lower ureters were anatomically dissected；The second ICG injection via intravenous administration revealed the vessels supplying the upper kidney，and the blood supply to the upper kidney was blocked；After the third ICG injection via intravenous administration，the normal lower kidney showed fluorescence imaging，while the ischemic upper kidney did not. The upper kidney was resected along the anatomical boundary between the upper and lower kidneys.Results:All 7 surgeries were successfully completed，with an average surgical time of（155.1 ± 22.7）min；Intraoperative blood loss was（12.5 ± 8.7）ml；postoperative hospital stay was（5.2 ± 1.7）days. Postoperative follow-up duration was（9.2 ± 3.5）months，with preoperative concomitant urinary tract infection and post-micturition dribbling symptoms resolved. No cases of ureteral stump effusion or urinary leakage were observed postoperatively. At the 3-month postoperative follow-up SPECT examination，no loss of lower kidney function was detected.Conclusions:The application of ICG-NIRF imaging technology in robotic-assisted laparoscopic heminephrectomy for children with duplicated kidneys is easy to perform and safe. Its main advantage is the ability to clearly identify normal ureters，blood vessels of non-functional kidneys，and the boundary between the upper and lower halves of the kidney，thereby guiding the optimization of surgical strategies.

Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68-5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13-3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.
Humans ; Prostatectomy/adverse effects* ; Robotic Surgical Procedures/methods* ; Male ; Urethra/surgery* ; Urinary Incontinence/prevention & control* ; Postoperative Complications/etiology* ; Prostatic Neoplasms/surgery* ; Organ Sparing Treatments/methods*

Objective To investigate the value of CT perfusion imaging (CTP) combined with serum eicosapentaenoic acid (EPA)/arachidonic acid (AA) in predicting hemorrhage transformation and short-term prognosis after thrombolysis in acute ischemic stroke (AIS) patients with leukoaraiosis. Methods Ninety-eight AIS patients with leukoaraiosis admitted to the department of neurology of our hospital from January 2021 to December 2022 were selected and divided into the hemorrhage transformation group and non-hemorrhage transformation group according to whether hemorrhage transformation occurred after thrombolysis. The Fazekas scale was used to evaluate the leukoaraiosis of the patients. CTP parameters and EPA/AA were compared between patients in the two groups and patients with different degrees of leukoaraiosis in the hemorrhage transformation group. The predictive value of CTP parameters and EPA/AA on the occurrence of hemorrhage transformation was evaluated by receiver operating characteristic (ROC) curve. The prognosis was assessed according to the modified Rankin scale (mRS) score 1 month after thrombolysis;the linear and linear combinations are used to evaluate the linear relationship between variables;the ROC curve was used to evaluate the predictive value of CTP parameters and EPA/AA in the short-term prognosis of patients. Results The reactive cerebral blood flow (rCBF),reactive cerebral blood volume (rCBV),CTP integration index and EPA/AA in the hemorrhage transformation group were significantly lower than those in the non-hemorrhage transformation group (P<0.05),while the relative time to peak (rTTP) was significantly longer than that in the non-hemorrhage transformation group (P<0.05). The incidence of hemorrhage transformation increased with the increase of leukoaraiosis degree (P<0.05). In the hemorrhage transformation group,rCBF,rCBV,CTP integration index and EPA/AA of patients with mild leukoaraiosis were higher than those of patients with moderate-severe leukoaraiosis (P<0.05). In patients with mild leukoaraiosis,the area under the curve (AUC) of rCBF and EPA/AA in predicting hemorrhage transforma-tion were 0.712 and 0.720,respectively (P<0.05);in patients with moderate-severe leukoaraiosis,the AUC of rCBF,rCBV,rTTP,CTP integration index and EPA/AA in predicting hemorrhage transformation were 0.738,0.714,0.717,0.739 and 0.742,respectively (P<0.05). Among the 98 patients received thrombolysis,35 patients had a poor prognosis. The AUC of rCBF,rCBV,CTP integration index and EPA/AA in predicting short-term prognosis were 0.742,0.732,0.704 and 0.738,respectively,and the AUC of the four combined prediction was 0.968. Conclusion CTP parameters and EPA/AA have a certain predictive value for the occurrence of hemorrhage transformation after thrombolysis in AIS patients with leukoaraiosis,and rCBV,rCBF,CTP integration index and EPA/AA are important influencing factors of the short-term prognosis for these patients.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Objective To investigate the value of CT perfusion imaging (CTP) combined with serum eicosapentaenoic acid (EPA)/arachidonic acid (AA) in predicting hemorrhage transformation and short-term prognosis after thrombolysis in acute ischemic stroke (AIS) patients with leukoaraiosis. Methods Ninety-eight AIS patients with leukoaraiosis admitted to the department of neurology of our hospital from January 2021 to December 2022 were selected and divided into the hemorrhage transformation group and non-hemorrhage transformation group according to whether hemorrhage transformation occurred after thrombolysis. The Fazekas scale was used to evaluate the leukoaraiosis of the patients. CTP parameters and EPA/AA were compared between patients in the two groups and patients with different degrees of leukoaraiosis in the hemorrhage transformation group. The predictive value of CTP parameters and EPA/AA on the occurrence of hemorrhage transformation was evaluated by receiver operating characteristic (ROC) curve. The prognosis was assessed according to the modified Rankin scale (mRS) score 1 month after thrombolysis;the linear and linear combinations are used to evaluate the linear relationship between variables;the ROC curve was used to evaluate the predictive value of CTP parameters and EPA/AA in the short-term prognosis of patients. Results The reactive cerebral blood flow (rCBF),reactive cerebral blood volume (rCBV),CTP integration index and EPA/AA in the hemorrhage transformation group were significantly lower than those in the non-hemorrhage transformation group (P<0.05),while the relative time to peak (rTTP) was significantly longer than that in the non-hemorrhage transformation group (P<0.05). The incidence of hemorrhage transformation increased with the increase of leukoaraiosis degree (P<0.05). In the hemorrhage transformation group,rCBF,rCBV,CTP integration index and EPA/AA of patients with mild leukoaraiosis were higher than those of patients with moderate-severe leukoaraiosis (P<0.05). In patients with mild leukoaraiosis,the area under the curve (AUC) of rCBF and EPA/AA in predicting hemorrhage transforma-tion were 0.712 and 0.720,respectively (P<0.05);in patients with moderate-severe leukoaraiosis,the AUC of rCBF,rCBV,rTTP,CTP integration index and EPA/AA in predicting hemorrhage transformation were 0.738,0.714,0.717,0.739 and 0.742,respectively (P<0.05). Among the 98 patients received thrombolysis,35 patients had a poor prognosis. The AUC of rCBF,rCBV,CTP integration index and EPA/AA in predicting short-term prognosis were 0.742,0.732,0.704 and 0.738,respectively,and the AUC of the four combined prediction was 0.968. Conclusion CTP parameters and EPA/AA have a certain predictive value for the occurrence of hemorrhage transformation after thrombolysis in AIS patients with leukoaraiosis,and rCBV,rCBF,CTP integration index and EPA/AA are important influencing factors of the short-term prognosis for these patients.

Objective:Exploring the efficacy of indocyanine green（ICG）near-infrared fluorescence（NIRF）imaging technology in robotic-assisted laparoscopic partial nephrectomy for children with duplicated kidneys.Methods:A retrospective analysis was conducted on the medical records of 7 children with duplicated kidneys admitted to Guizhou Provincial People's Hospital from December 2023 to September 2024，including 3 males and 4 females. The patients with a median age of 36（2，132）months. All cases of duplicated kidneys were located at the renal pole，with 5 on the left side and 2 on the right side. All 7 patients had a history of worsening hydronephrosis，with 4 having a history of urinary tract infection and 1 accompanied by urinary incontinence（urine leakage outside the normal voiding period）. Preoperative diagnosis was confirmed via enhanced CT of the urinary tract，diuretic renal dynamic imaging（SPECT），and voiding cystourethrography. One case had an ectopic ureteral opening. One case had recurrent urinary tract infections following ureteral cyst fenestration surgery，and five cases had terminal ureteral obstruction. All seven cases showed that the functional capacity of the duplicated upper kidney was <10%. All 7 cases underwent robot-assisted laparoscopic repeated nephrectomy of the upper kidney using ICG-NIRF technology. Intraoperative ICG fluorescence imaging was performed in three stages：a catheter was inserted through the lower kidney ureter，and after the first injection of ICG，green fluorescence was observed in the lower kidney ureter. Under fluorescence guidance，the upper and lower ureters were anatomically dissected；The second ICG injection via intravenous administration revealed the vessels supplying the upper kidney，and the blood supply to the upper kidney was blocked；After the third ICG injection via intravenous administration，the normal lower kidney showed fluorescence imaging，while the ischemic upper kidney did not. The upper kidney was resected along the anatomical boundary between the upper and lower kidneys.Results:All 7 surgeries were successfully completed，with an average surgical time of（155.1 ± 22.7）min；Intraoperative blood loss was（12.5 ± 8.7）ml；postoperative hospital stay was（5.2 ± 1.7）days. Postoperative follow-up duration was（9.2 ± 3.5）months，with preoperative concomitant urinary tract infection and post-micturition dribbling symptoms resolved. No cases of ureteral stump effusion or urinary leakage were observed postoperatively. At the 3-month postoperative follow-up SPECT examination，no loss of lower kidney function was detected.Conclusions:The application of ICG-NIRF imaging technology in robotic-assisted laparoscopic heminephrectomy for children with duplicated kidneys is easy to perform and safe. Its main advantage is the ability to clearly identify normal ureters，blood vessels of non-functional kidneys，and the boundary between the upper and lower halves of the kidney，thereby guiding the optimization of surgical strategies.