Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Real-time acquisition of pulmonary ventilation and perfusion information through thoracic electrical impedance tomography (EIT) holds significant clinical value. This study proposes a novel method based on the rime (RIME) algorithm-optimized variational mode decomposition (VMD) to separate lung ventilation and perfusion signals directly from raw voltage data prior to EIT image reconstruction, enabling independent imaging of both parameters. To validate this approach, EIT data were collected from 16 healthy volunteers under normal breathing and inspiratory breath-holding conditions. The RIME algorithm was employed to optimize VMD parameters by minimizing envelope entropy as the fitness function. The optimized VMD was then applied to separate raw data across all measurement channels in EIT, with spectral analysis identifying relevant components to reconstruct ventilation and perfusion signals. Results demonstrated that the structural similarity index (SSIM) between perfusion images derived from normal breathing and breath-holding states averaged approximately 84% across all 16 subjects, significantly outperforming traditional frequency-domain filtering methods in perfusion imaging accuracy. This method offers a promising technical advancement for real-time monitoring of pulmonary ventilation and perfusion, holding significant value for advancing the clinical application of EIT in the diagnosis and treatment of respiratory diseases.
Humans ; Electric Impedance ; Algorithms ; Tomography/methods* ; Pulmonary Ventilation/physiology* ; Lung/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Adult

Methods: Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1, 2020, to October 30, 2021 were enrolled as the research participants in the study. They were assigned to two groups based on traditional Chinese medicine (TCM) syndrome types: heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group. Healthy volunteers who underwent health check-ups in the Health Management Department were included as healthy group following the random number table method. The tears of the patients and the healthy volunteer participants were tested by high-performance liquid chromatography-mass spectrometry (LC-MS). The differential metabolites were screened out by multivariate statistical analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed on the differential metabolites. Finally, the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites. Results: A total of 32 dry eye patients were enrolled, including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern. Fourteen healthy volunteers were included as healthy group. There were no significant differences in baseline characteristics among the three groups (P > 0.05). A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group, mainly including lipids, lipid-like molecules, organic acids and their derivatives, organic heterocyclic compounds, and nucleosides and their analogues. For heat stagnation in liver meridian pattern group, 112 metabolites were determined, mainly including organic acids and their derivatives, lipids, and lipid-like molecules. The KEGG enrichment results of pathways and the relative content analysis of differential markers demonstrate that purine metabolism and caffeine metabolism pathways are common metabolic characteristics of all dry eyes. Among them, deoxyinosine monophosphate (dIMP) and 2-(formamido)-N1-(5-phospha-D-ribosyl) acetamidine can serve as their biomarkers. The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation, ovarian steroidogenesis, cholesterol metabolism, pyrimidine metabolism, and bile secretion (P < 0.05). Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine, leucine, and isoleucine biosynthesis pathways (P < 0.05). Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification. Different patterns of dry eye syndrome exhibit typical characteristics in the types and concentrations of metabolites, which correspond to the syndrome classification in TCM. This study initially confirms the rationality of TCM syndrome classification and provides significant reference for the mechanism of dry eye and drug development.

Objective:To analyze the risk factors affecting the efficacy of arterial balloon occlusion intervention in cesarean sections for women with placenta accreta spectrum (PAS).Methods:A retrospective study was conducted on 55 PAS patients who underwent arterial balloon occlusion during cesarean sections in the obstetrics department of the First Affiliated Hospital of Guangxi Medical University from January 2015 to March 2021. The patients were divided into two groups based on surgical blood loss: ≥2 000 ml group (27 cases) and <2 000 ml group (28 cases). Baseline data, surgical management, and pregnancy outcomes were analyzed between the two groups. For patients who underwent MRI, prenatal MRI characteristics were analyzed. Intergroup comparisons were performed using independent samples t-test, Mann-Whitney U test, or Chi-square test (or Fisher's exact test). Bonferroni correction was used for multiple comparisons. Results:(1) The variation in patients' bleeding volume across different years during the study period was not statistically significant. The proportion of placenta percreta in the ≥2 000 ml blood loss group was significantly higher than in the <2 000 ml group [placenta accreta, increta, and percreta in both groups were 0.0% (0/27) vs. 7.1% (2/28); 25.9% (7/27) vs. 53.6% (15/28); and 74.1% (20/27) vs. 39.3% (11/28), respectively; Fisher's exact test, P=0.019]. (2) The ≥2 000 ml group showed a trend towards higher rates of hysterectomy and failed uterine preservation after placental removal compared to the <2 000 ml group [25.9% (7/27) vs. 3.6% (1/28), Fisher's exact test], but the difference was not statistically significant ( P=0.074). (3) The ≥2 000 ml group had significantly higher blood loss, transfusion of ≥5 units of red blood cells, incidence of disseminated intravascular coagulation, longer surgery time, and higher postoperative transfer to intensive care unit rates compared to the <2 000 ml group [3 600 ml (2 550-5 050 ml) vs. 1 100 ml (600-1 500 ml), Z=756.00; 77.8% (21/27) vs. 21.4% (6/28), χ2=17.40; 33.3% (9/27) vs. 0.0% (0/28), Fisher's exact test; (253±94) min vs. (150±57) min, t=4.92; 40.7% (11/27) vs. 3.6% (1/28), χ2=11.13; all P<0.05]. The bladder injury rate in the ≥2 000 ml group showed a trend towards being higher than in the <2 000 ml group, but the difference was not statistically significant [22.2% (6/27) vs. 3.6% (1/28), Fisher's exact test, P=0.051]. There were no statistically significant differences in other maternal and neonatal outcomes between the two groups. (4) Among the study subjects, 50 patients had prenatal MRI data, with 22 in the ≥2 000 ml group and 28 in the <2 000 ml group. The ≥2 000 ml group had a significantly higher proportion of local exophytic masses, asymmetric placental thickening/shape, and placental invasion in the S2 region compared to the <2 000 ml group [81.8% (18/22) vs. 53.6% (15/28), χ2=4.38; 81.8% (18/22) vs. 50.0% (14/28), χ2=5.41; 95.5% (21/22) vs. 53.6% (15/28), χ2=10.72; all P<0.05]. Conclusions:When the placenta invades the S2 region and the depth is invasive, arterial balloon occlusion in cesarean sections for PAS still faces a high risk of massive hemorrhage. Prenatal MRI should focus on assessing the extent and depth of placental invasion to identify potentially severe PAS cases, thereby optimizing the clinical application of arterial balloon occlusion.

Objective:To analyze the risk factors affecting the efficacy of arterial balloon occlusion intervention in cesarean sections for women with placenta accreta spectrum (PAS).Methods:A retrospective study was conducted on 55 PAS patients who underwent arterial balloon occlusion during cesarean sections in the obstetrics department of the First Affiliated Hospital of Guangxi Medical University from January 2015 to March 2021. The patients were divided into two groups based on surgical blood loss: ≥2 000 ml group (27 cases) and <2 000 ml group (28 cases). Baseline data, surgical management, and pregnancy outcomes were analyzed between the two groups. For patients who underwent MRI, prenatal MRI characteristics were analyzed. Intergroup comparisons were performed using independent samples t-test, Mann-Whitney U test, or Chi-square test (or Fisher's exact test). Bonferroni correction was used for multiple comparisons. Results:(1) The variation in patients' bleeding volume across different years during the study period was not statistically significant. The proportion of placenta percreta in the ≥2 000 ml blood loss group was significantly higher than in the <2 000 ml group [placenta accreta, increta, and percreta in both groups were 0.0% (0/27) vs. 7.1% (2/28); 25.9% (7/27) vs. 53.6% (15/28); and 74.1% (20/27) vs. 39.3% (11/28), respectively; Fisher's exact test, P=0.019]. (2) The ≥2 000 ml group showed a trend towards higher rates of hysterectomy and failed uterine preservation after placental removal compared to the <2 000 ml group [25.9% (7/27) vs. 3.6% (1/28), Fisher's exact test], but the difference was not statistically significant ( P=0.074). (3) The ≥2 000 ml group had significantly higher blood loss, transfusion of ≥5 units of red blood cells, incidence of disseminated intravascular coagulation, longer surgery time, and higher postoperative transfer to intensive care unit rates compared to the <2 000 ml group [3 600 ml (2 550-5 050 ml) vs. 1 100 ml (600-1 500 ml), Z=756.00; 77.8% (21/27) vs. 21.4% (6/28), χ2=17.40; 33.3% (9/27) vs. 0.0% (0/28), Fisher's exact test; (253±94) min vs. (150±57) min, t=4.92; 40.7% (11/27) vs. 3.6% (1/28), χ2=11.13; all P<0.05]. The bladder injury rate in the ≥2 000 ml group showed a trend towards being higher than in the <2 000 ml group, but the difference was not statistically significant [22.2% (6/27) vs. 3.6% (1/28), Fisher's exact test, P=0.051]. There were no statistically significant differences in other maternal and neonatal outcomes between the two groups. (4) Among the study subjects, 50 patients had prenatal MRI data, with 22 in the ≥2 000 ml group and 28 in the <2 000 ml group. The ≥2 000 ml group had a significantly higher proportion of local exophytic masses, asymmetric placental thickening/shape, and placental invasion in the S2 region compared to the <2 000 ml group [81.8% (18/22) vs. 53.6% (15/28), χ2=4.38; 81.8% (18/22) vs. 50.0% (14/28), χ2=5.41; 95.5% (21/22) vs. 53.6% (15/28), χ2=10.72; all P<0.05]. Conclusions:When the placenta invades the S2 region and the depth is invasive, arterial balloon occlusion in cesarean sections for PAS still faces a high risk of massive hemorrhage. Prenatal MRI should focus on assessing the extent and depth of placental invasion to identify potentially severe PAS cases, thereby optimizing the clinical application of arterial balloon occlusion.

Creatinine levels in biological fluids are important indicators for the clinical evaluation of renal function. Creatinase (CRE, EC3.5.3.3) is one of the key enzymes in the enzymatic measurement of creatinine concentration, and it is also the rate-limiting enzyme in the whole enzymatic cascade system. The poor catalytic activity of CRE severely limits its clinical and industrial applications. To address this issue, a semi-rational design is applied to increase the activity of a creatinase from Alcaligenes sp. KS-85 (Al-CRE). By high-throughput screen of saturation mutagenesis libraries on the selected hotspot mutations, multiple variant enzymes with increased activity are obtained. The five-point best variant enzyme (I304L/F395V/K351V/Y63S/Q88A) were further obtained by recombine the improved mutations sites that to showed a 2.18-fold increased specific activity. Additionally, structure analysis is conducted to understand the mechanism of the activity change. This study paves the way for a better practical application of creatinase and may help further understand its catalytic mechanism.
Creatinine ; Mutagenesis, Site-Directed ; Ureohydrolases/genetics* ; Catalysis

Objective To confirm the optimal tissue sampling location of current injury combined with the histopathological observation in specific parts of electrocution based on previous animal experiments. Methods Twenty-three human cases from the autopsy through the hand-to-foot circuit pathway were analyzed. Additional ten autopsy patients who died from traffic accidents and sudden cardiac attacks were used as the control group. All cases were extracted the soft tissues from the upper anterior wrist and medial malleolus to further observe and analysis the L/S axis ratio of the nuclei of the skeletal muscle cells (SkMCs) and artery smooth muscle cells (ASMCs). Results The age of the 23 eligible electrical deaths ranged from 19 to 59 years, including 19 cases were male and 4 cases were female. 3 cases were high-voltage 20 cases were low voltage. The occurrence rate of electric marks averaged 31.18% in all cases. The incidence of the classical arborizing pattern of fine branching was 36.4%, appearing on the pleura in 5 cases (22.7%). The nuclei of the SkMCs and ASMCs nuclei in the anterior wrist and medial malleolus within the electrical current pathway were obviously stretched, narrowed, and coalesced, presenting a nuclear polarization and arranging as line-like and moniliform patterns. The L/S axis ratio of those nuclei in the anterior wrist and medial malleolus were markedly increased as compared with the control group (p < 0.001). Through the ROC curve analysis, the critical diagnostic values of the L/S axis ratio of those nuclei were respectively 4.84 and 3.81. Conclusion These findings suggest that the soft tissues of the anterior wrist and/or the medial malleolus, as the narrowest parts of the limbs, could be used as the sites for tissue sampling and considered as necessary locations for histopathological examinations to determine the electrocution in medicolegal identification.

Objective To observe the impact of ginkgo biloba extract in rats with chronic cerebral ischemia on the expression of PSD-95 protein and the content of amino acid neurotransmitter.Methods A total of 42 SD rats were divided into the sham group (n=12), the model group (n=14) and the ginkgo biloba extract group (n=14) by random number table method. Cerebral ischemia rats were produced by permanent ligation of bilateral common carotid arteries . The rats in the ginkgo biloba group were intrgastric administrated with ginkgo biloba extract suspension 28 mg/kg daily for 40 days, since 2 hours later after the surgery. The rats in the sham and model groups were intragastric administrated with equal-Volume nomal saline daily for 40 days, since 2 hours later after the surgery. The expression of PSD-95 protein was detected by immunohistochemistry techniques with image analysis. The content of Glu and GABA in the thalamus was determinated by OPA-pre-column derivatization and HPLC fluorescence detection method.Results The expression of PSD-95 protein (cortex was 212.58 ± 45.02vs.244.20 ± 34.28, thalamus was 132.33 ± 28.32 vs.272.00 ± 62.14) were significantly lower in the cortex and thalamus of the model group than those of the sham group (P<0.01). The content of GABA (6 081.46 ± 2 388.91 mmol/Lvs.8 280.45 ± 3 388.49 mmol/L) in the thalamus of the model group rats was significantly lower than the sham group (P<0.05). Ginkgo biloba extract could significantly improve the expression of PSD-95 protein (cortex was 237.89 ± 34.41 vs.212.58 ± 45.02, thalamus was 226.18 ± 75.80 vs. 132.33 ± 28.32) in the cortex and thalamus of chronic cerebral ischemia rats (P<0.01), and significantly improve the content of Glu and GABA (Glu was 10 523.78 ± 3 639.72 mmol/L vs.6 081.46 ± 2 388.91 mmol/L, and GABA was 18 440.93 ± 7 476.88 mmol/Lvs.11 239.83 ± 4 411.79 mmol/L) in thalamus with chronic cerebral ischemic rats compared with the model group rats (P<0.01).Conclusion Ginkgo biloba extract could regulate the levels of Glu, GABA and selectly regulate the PSD-95 experssion in the cortex and thalamus of cerebral ischemia rats.

Objective To investigate the safety and feasibility of totally laparoscopic radical resection of gallbladder cancer.Methods The retrospective cross-sectional descriptive study was adopted.The clinical data of 30 patients who underwent laparoscopic radical resection of gallbladder cancer at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2013 to August 2015 were collected.The patients received synchronous hepatic segmental or extrahepatic bile duct resection according to the conditions of patients,and choledochojejunostomy was applied to patients undergoing extrahepatic bile duct resection.The patients accepted postoperative adjuvant chemotherapy according to the results of postoperative pathological examination.Observation indicators included (1) operation situations,including surgical procedures,operation time,volume of intraoperative blood loss and number of lymph node dissected,(2) postoperative situations,including time for outoff-bed activity,time for diet intake,time of drainage tube removal,occurrence of complications and duration of hospital stay,(3) results of postoperative pathological examination,including tumor stage and surgical margin,(4) postoperative adjuvant treatment,(5) follow-up situation including the survival of patients,tumor recurrence and metastasis.The follow-up using outpatient examination and telephone interview was performed to detect the survival of patients and tumor recurrence and metastasis up to December 2015.Count data were represented as average (range).Results All the 30 patients underwent successful laparoscopic radical resection of gallbladder cancer combined with hepatic S4b and S5 resection + lymph node dissection at N1 region.Six patients with obstructive jaundice caused by tumor invaded to extrahepatic bile duct underwent combined laparoscopic extrahepatic bile duct resection + Roux-en-Y hepaticojejunostomy,without perioperative death.The average operation time,average volume of intraoperative blood loss and average number of intraoperative lymph node dissected were 238 minutes (range,178-430 minutes),250 mL (range,200-600 mL) and 7 (range,4-15),respectively.(2) The patients got out-off-bed activity and normal diet intake at postoperative day 2,with a average time of drainage tube removal of 3 days (range,0-25 days) and an average duration of hospital stay of 5 days (range,3-28 days).Two patients with complications were cured by symptomatic treatment.(3) Results of postoperative pathological examination showed that all the patients received R0 resection,and pathological stage showed that 12 patients were detected in Ⅰ B stage,10 in Ⅱ stage,7 in ⅢA stage and 1 in ⅢB stage.(4) One patient in Ⅲ B stage (pT3N1 M0 stage) received gemcitabine + cisplatin chemotherapy and other patients didn't receive the adjuvant treatment.(5) All the patients were followed up for a median time of 16 months (range,4-32 months),without tumor recurrence and metastasis at Trocar puncture site.There were 25 patients with tumor-free survival and 5 patiens died of tumor recurrence.Conclusion Laparoscopic radical resection of gallbladder cancer is technically safe and feasible,with a satisfactory short-term outcome.

Ulcerative colitis (UC) is a chronic non-specific disease of the rectum and colon. The disease cause is still unclear. Due to the repeated episodes of UC, the treatment is very difficult. There are serious impact on pa-tients' life and work. According to the current UC condition and existed problems with Chinese medicine treat-ment and in combination with experiences of new Chinese medicine drug development of the author, a new Chi-nese medicine drug research idea of UC has been proposed. It includes the establishment of UC animal model in line with the characteristics of Chinese medicine and the selection of appropriate clinical treatment targets.