ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

The rabies virus(RABV)that causes rabies mainly attacks the peripheral and central nervous systems.In the later stages of infection,it is scattered in the salivary glands and transmit-ted to other susceptible animals through infectious saliva.To study dispersion of the RABV in the three pairs of salivary gland tissues,the street strain PB4 of the RABV was inoculated into 21-day-old female mice through the hind limb muscles.During the moribund stage of the mice,the sublin-gual gland,submandibular gland and parotid gland were collected,respectively.The TCID50 titer of RABV in the three kinds of glands of the mice and the copy number of the RABV N gene were de-tected,and RABV in different salivary glands was observed by immunofluorescence.The results showed that PB4 was dispersed in all three kinds of salivary glands of the mice,with the largest a-mounts in the parotid gland,followed by the submandibular gland,and the lowest amount in the sublingual gland.Three-month-old dogs were inoculated with PB4 through the cranial cavity,and saliva were collected every 12 h after inoculation.The saliva samples were detected by TCID50 and RT-qPCR.And during the moribund stage of the dogs when the disease occurred,the three pairs of salivary glands were collected.Through the determination of the TCID50 titer,RT-qPCR and immu-nofluorescence detection,it was demonstrated that among the three different salivary glands of the dogs,the largest amount of PB4 was found in the parotid gland and the lowest in the sublingual gland.Our results in mice and dogs clearly proved that the parotid gland was consistently found to exhibit the highest content of street RABV among the three major salivary glands,which could en-rich experimental data for analyzing the dispersion of RABV in the salivary glands and interpreta-tion of the intermittent secretion of saliva in clinically rabid dogs.

The rabies virus(RABV)that causes rabies mainly attacks the peripheral and central nervous systems.In the later stages of infection,it is scattered in the salivary glands and transmit-ted to other susceptible animals through infectious saliva.To study dispersion of the RABV in the three pairs of salivary gland tissues,the street strain PB4 of the RABV was inoculated into 21-day-old female mice through the hind limb muscles.During the moribund stage of the mice,the sublin-gual gland,submandibular gland and parotid gland were collected,respectively.The TCID50 titer of RABV in the three kinds of glands of the mice and the copy number of the RABV N gene were de-tected,and RABV in different salivary glands was observed by immunofluorescence.The results showed that PB4 was dispersed in all three kinds of salivary glands of the mice,with the largest a-mounts in the parotid gland,followed by the submandibular gland,and the lowest amount in the sublingual gland.Three-month-old dogs were inoculated with PB4 through the cranial cavity,and saliva were collected every 12 h after inoculation.The saliva samples were detected by TCID50 and RT-qPCR.And during the moribund stage of the dogs when the disease occurred,the three pairs of salivary glands were collected.Through the determination of the TCID50 titer,RT-qPCR and immu-nofluorescence detection,it was demonstrated that among the three different salivary glands of the dogs,the largest amount of PB4 was found in the parotid gland and the lowest in the sublingual gland.Our results in mice and dogs clearly proved that the parotid gland was consistently found to exhibit the highest content of street RABV among the three major salivary glands,which could en-rich experimental data for analyzing the dispersion of RABV in the salivary glands and interpreta-tion of the intermittent secretion of saliva in clinically rabid dogs.

Objective To compare image quality and clinical usefulness between single breath-hold three-dimensional magnetic resonance cholangiopancreatography with compressed sensing(3D BH-CS-MRCP)and with gradient and spin-echo(3D BH-GRASE-MRCP)and conventional three-dimensional breath-triggered magnetic resonance cholangiopancreatography(3D RT-MRCP).Methods A retrospective analysis was performed in 48 patients(26 males and 22 females,mean age of 53.14±15.19 years),who underwent 3D BH-GRASE-MRCP,3D BH-CS-MRCP and 3D RT-MRCP from September to December 2023.Pancreaticobiliary duct visibility,motion artifacts,background suppression,and overall image quality were scored on a 5-point scale by two radiologists.The relative contrast ratio of three bile duct segmentations(common bile duct,left and right intrahepatic bile ducts)were calculated,and the acquisition time of the three sequences was recorded.Friedman test with a post-hoc test was performed to compare image acquisition time,qualitative and quantitative results.Results The acquisition time was significantly shorter in the two breath-hold groups than for conventional 3D RT-MRCP(P＜0.001).There were no significant differences in overall image quality,motion artifacts,common bile duct and primary branch of intrahepatic bile duct among the three groups.The relative contrast ratio,intrahepatic biliary secondary branch visibility and background suppression score of 3D RT-MRCP and BH-CS-MRCP were significantly higher than those of BH-GRASE-MRCP(P＜0.01).The pancreatic duct(proximal,middle,distal)visibility score of 3D RT-MRCP was significantly better than that of BH-GRASE-MRCP(P=0.002,0.043,0.001),but the gallbladder and gallbladder duct visibility score of BH-GRASE-MRCP was higher than that of 3D RT-MRCP(P=0.036).There was no significant difference between 3D RT-MRCP and BH-CS-MRCP scores except for the middle and distal pancreatic duct visibility.Conclusion Breath-hold 3D MRCP with GRASE and CS can give us feasible options for pancreaticobiliary diagnosis,which significantly shortens the acquisition time without reducing the overall image quality.Compared with BH-GRASE-MRCP,BH-CS-MRCP has better consistency in pancreaticobiliary duct visibility and background suppression.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Objective:To explore the psychological vulnerability characteristics of patients after percutaneous coronary intervention (PCI) based on symptom network analysis, and to provide evidence for maintining their psychological health.Methods:Using a cross-sectional survey method, from October 2023 to March 2024, a convenience sampling approach was employed to conduct a questionnaire survey among patients who underwent percutaneous coronary intervention (PCI) in the general ward of the Cardiology Department at Peking University Third Hospital. The survey involved a general information questionnaire and Mental Vulnerability Questionnaire. The R language was used to construct a symptom network to describe the relationship between each symptom of patients′psychological vulnerability, and its centrality index was calculated.Results:A total of 260 post-PCI patients were enrolled, including191 males and 69 females, with a mean age of (62.38 ± 12.91) years and a total psychological vulnerability score of (47.25 ± 13.18). Multiple linear regression analysis showed that the level of mental vulnerability was higher in patients with female gender ( β = 0.207, P = 0.001) and higher number of comorbidities/past history ( β = 0.126, P = 0.039). In the symptom network analysis, the symptoms with the highest node strength, tight centrality, and mediator centrality were "You often feeling unwell" ( rs = 1.25, rc = 0.003 45, rb = 2.61), "You always in a bad mood" ( rs = 1.15) and "You often have anxiety attacks" ( rs = 1.13) were second only to "You often feeling unwell" in the center of intensity. Conclusions:The core symptom of psychological vulnerability in post-PCI patients is "You often feeling unwell", and mental symptoms are in a more central position. Nursing staff should take mental symptoms as the target of intervention, and strengthen the holistic care for patients′physical-psychological-mental symptoms, so as to effectively reduce the level of psychological vulnerability of the patients, and to maintain their psychological health.

Objective To compare image quality and clinical usefulness between single breath-hold three-dimensional magnetic resonance cholangiopancreatography with compressed sensing(3D BH-CS-MRCP)and with gradient and spin-echo(3D BH-GRASE-MRCP)and conventional three-dimensional breath-triggered magnetic resonance cholangiopancreatography(3D RT-MRCP).Methods A retrospective analysis was performed in 48 patients(26 males and 22 females,mean age of 53.14±15.19 years),who underwent 3D BH-GRASE-MRCP,3D BH-CS-MRCP and 3D RT-MRCP from September to December 2023.Pancreaticobiliary duct visibility,motion artifacts,background suppression,and overall image quality were scored on a 5-point scale by two radiologists.The relative contrast ratio of three bile duct segmentations(common bile duct,left and right intrahepatic bile ducts)were calculated,and the acquisition time of the three sequences was recorded.Friedman test with a post-hoc test was performed to compare image acquisition time,qualitative and quantitative results.Results The acquisition time was significantly shorter in the two breath-hold groups than for conventional 3D RT-MRCP(P＜0.001).There were no significant differences in overall image quality,motion artifacts,common bile duct and primary branch of intrahepatic bile duct among the three groups.The relative contrast ratio,intrahepatic biliary secondary branch visibility and background suppression score of 3D RT-MRCP and BH-CS-MRCP were significantly higher than those of BH-GRASE-MRCP(P＜0.01).The pancreatic duct(proximal,middle,distal)visibility score of 3D RT-MRCP was significantly better than that of BH-GRASE-MRCP(P=0.002,0.043,0.001),but the gallbladder and gallbladder duct visibility score of BH-GRASE-MRCP was higher than that of 3D RT-MRCP(P=0.036).There was no significant difference between 3D RT-MRCP and BH-CS-MRCP scores except for the middle and distal pancreatic duct visibility.Conclusion Breath-hold 3D MRCP with GRASE and CS can give us feasible options for pancreaticobiliary diagnosis,which significantly shortens the acquisition time without reducing the overall image quality.Compared with BH-GRASE-MRCP,BH-CS-MRCP has better consistency in pancreaticobiliary duct visibility and background suppression.

Objective:To explore the effects of radical resection of pelvic autonomic nerve sparing cervical cancer on urodynamics, sexual function and prognosis of patients with cervical cancer.Methods:A total of 76 patients with cervical cancer admitted to Dingzhou People’s Hospital from Jan. 2021 to Jan. 2023 were selected as research objects, and all patients were divided into control group and study group by random number table method, with 38 cases in each group. The control group was treated with traditional laparoscopic radical cervicectomy, and the study group was treated with laparoscopic radical cervicectomy preserving pelvic autonomic nerve. Perioperative indexes, preoperative and postoperative urodynamics, tumor markers, sexual function and postoperative adverse reactions were compared between the two groups.Results:The operation time of the observation group was longer than that of the control group ( P<0.05). The exhaust time and defecation time of the observation group were lower in the observation group than in the control group ( P<0.05). There was no significant difference in the amount of blood loss or lymph node dissection between the two groups ( P>0.05). There was no significant difference in urodynamic indexes between the two groups before surgery ( P>0.05). In the observation group after surgery, the bladder compliance, maximum urine flow rate and maximum detrusor systolic blood pressure were (81.55±13.18 mL/cm H 20, 20.46±4.65 L/s, 35.09±7.41 cm H 20), while they were (60.14±10.27) mL/cm H 20, (14.48±3.92) L/s, (28.15±6.94) cm H 20 in the control group. The observation group were higher than the control group ( P<0.05). There was no significant difference in maximum bladder volume between the two groups ( P>0.05). There was no significant difference in sexual function scores between the two groups before surgery ( P>0.05). The scores of sexual desire, vaginal wetness and pain, sexual arousal and orgasm, and sexual satisfaction in the observation group were higher than those in the control group ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05) . Conclusion:Radical resection of pelvic autonomic nerve preserving cervical cancer can improve urodynamic indexes and sexual function of patients with cervical cancer, and has the same efficacy as conventional laparoscopic radical resection of cervical cancer without increasing adverse reactions, and has a good effect and safety.

This study aims to inquire about the fluctuations of ubiquitin-specific protease 47 on neu-roblastoma cells(Neuro-2a,N2a)infected by rabies virus(RABV).USP47 expression levels were detected after RABV infection in N2a cells through RT-qPCR,protein immunoblotting,and virus titer determination.The levels of RABV nucleoprotein and phosphoprotein gene and protein,and RABV titers in supernatants were analyzed during overexpression and knockdown of USP47.The results showed that RABV infection increased USP47 gene level in N2a cells.When overexpression of USP47,the levels of RABV N and P were increased,and the virus titers were also improved.Mo-reover,the level of interleukin-6(IL-6)genes decreased.Knocking down USP47 expression reduced levels of RABV N and P genes and proteins,lowered the virus titer,and elevated the IL-6 gene lev-el.The results suggest that USP47 promotes RABV infection and suppresses IL-6 expression.This finding lays the foundation for further investigation into the molecular mechanisms by which USP47 regulates RABV infection.

Objective:To explore the effects of radical resection of pelvic autonomic nerve sparing cervical cancer on urodynamics, sexual function and prognosis of patients with cervical cancer.Methods:A total of 76 patients with cervical cancer admitted to Dingzhou People’s Hospital from Jan. 2021 to Jan. 2023 were selected as research objects, and all patients were divided into control group and study group by random number table method, with 38 cases in each group. The control group was treated with traditional laparoscopic radical cervicectomy, and the study group was treated with laparoscopic radical cervicectomy preserving pelvic autonomic nerve. Perioperative indexes, preoperative and postoperative urodynamics, tumor markers, sexual function and postoperative adverse reactions were compared between the two groups.Results:The operation time of the observation group was longer than that of the control group ( P<0.05). The exhaust time and defecation time of the observation group were lower in the observation group than in the control group ( P<0.05). There was no significant difference in the amount of blood loss or lymph node dissection between the two groups ( P>0.05). There was no significant difference in urodynamic indexes between the two groups before surgery ( P>0.05). In the observation group after surgery, the bladder compliance, maximum urine flow rate and maximum detrusor systolic blood pressure were (81.55±13.18 mL/cm H 20, 20.46±4.65 L/s, 35.09±7.41 cm H 20), while they were (60.14±10.27) mL/cm H 20, (14.48±3.92) L/s, (28.15±6.94) cm H 20 in the control group. The observation group were higher than the control group ( P<0.05). There was no significant difference in maximum bladder volume between the two groups ( P>0.05). There was no significant difference in sexual function scores between the two groups before surgery ( P>0.05). The scores of sexual desire, vaginal wetness and pain, sexual arousal and orgasm, and sexual satisfaction in the observation group were higher than those in the control group ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05) . Conclusion:Radical resection of pelvic autonomic nerve preserving cervical cancer can improve urodynamic indexes and sexual function of patients with cervical cancer, and has the same efficacy as conventional laparoscopic radical resection of cervical cancer without increasing adverse reactions, and has a good effect and safety.