Objective To explore the mechanism by which gentiopicroside (GPS) prevents macrophage-mediated hepatic fibrosis by regulating the macrophage migration inhibitory factor (MIF)-secreted phosphoprotein 1 (SPP1) signaling pathway in hepatic stellate cells. Methods LX-2 cells were divided into control group, transforming growth factor β(TGF-β) group, and TGF-β combined with GPS (25, 50, 100, 150 μmol/mL) groups. Cell proliferation was detected by EDU assay, cell invasion was assessed by Transwell^TM assay, and the protein expressions of α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) were measured by Western blot. M1-type macrophage-conditioned medium (M1-CM) was used to treat LX-2 cells in the TGF-β group and TGF-β combined with GPS group. The concentrations of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) in the cell supernatant, as well as cell proliferation, invasion ability, and the expressions of α-SMA and COL1A1 were detected. Bioinformatics analysis was performed to identify the target intersections of GPS, hepatic fibrosis, and macrophage-related genes. Drug affinity responsive target stability (DARTS) experiments and Western blot were used to verify the regulatory effect of GPS on MIF. Furthermore, LX-2 cells were divided into control group, TGF-β group, TGF-β combined with M2-CM group, TGF-β and oe-NC combined with M2-CM group, and TGF-β and oe-MIF combined with M2-CM group to analyze the concentrations of iNOS and Arg1 in the cell supernatant, as well as changes in cell proliferation, invasion, and the expressions of α-SMA and COL1A1. LX-2 cells were also divided into control group, TGF-β group, TGF-β combined with oe-NC group, TGF-β combined with oe-MIF group, and TGF-β and oe-MIF combined with GPS group to determine the protein expressions of MIF and SPP1 by Western blot. A rat model of hepatic fibrosis was constructed to explore the potential therapeutic effects of GPS on hepatic fibrosis in vivo. Results Compared with the control group, the proliferation and invasion abilities of LX-2 cells in the TGF-β group were increased, and the protein expressions of α-SMA and COL1A1 were enhanced. GPS intervention inhibited the proliferation and invasion of LX-2 cells under TGF-β conditions and reduced the expressions of α-SMA and COL1A1. Compared with the control group, the concentration of iNOS in the cell supernatant of the TGF-β group was upregulated, while the concentration of Arg1 was decreased. M1-CM treatment further increased the concentration of iNOS, decreased the concentration of Arg1, and promoted cell proliferation and invasion, as well as upregulated the expressions of α-SMA and COL1A1 on the basis of TGF-β intervention. However, GPS could reverse the effects of M1-CM intervention. Bioinformatics analysis revealed that MIF was one of the target intersections of GPS, hepatic fibrosis, and macrophage-related genes, and GPS could target and inhibit its expression. Compared with the TGF-β group, after M2-CM intervention, the concentration of iNOS in the cell supernatant decreased, the concentration of Arg1 increased, the proliferation and invasion abilities of LX-2 cells were reduced, and the expressions of α-SMA and COL1A1 were weakened. However, overexpression of MIF reversed the effects of M2-CM intervention. Western blot results showed that compared with the control group, the protein expressions of MIF and SPP1 were enhanced in the TGF-β group. Overexpression of MIF further enhanced the expressions of MIF and SPP1, while GPS intervention inhibited the expressions of MIF and SPP1. In the animal experiment, GPS intervention treatment alleviated liver injury in rats with hepatic fibrosis and inhibited the expressions of MIF and SPP1, as well as α-SMA and COL1A1 in liver tissue. Conclusion GPS may prevent macrophage-mediated hepatic fibrosis by inhibiting the MIF-SPP1 signaling pathway in hepatic stellate cells.
Hepatic Stellate Cells/metabolism* ; Signal Transduction/drug effects* ; Macrophage Migration-Inhibitory Factors/genetics* ; Liver Cirrhosis/prevention & control* ; Macrophages/drug effects* ; Iridoid Glucosides/pharmacology* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Cell Line ; Collagen Type I/metabolism* ; Collagen Type I, alpha 1 Chain ; Intramolecular Oxidoreductases/genetics* ; Rats ; Transforming Growth Factor beta/pharmacology* ; Actins/metabolism*

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.

Objective To observe the effects of electroacupuncture auricular acupuncture points on depression-like behaviors and ventral dorsal tegmental area(VTA)TH,DRD1 and DRD2 induced in well acute stress disorder(ASD)mice.Methods Experiment 1:18 male C57 mice were divided into 9 control and 9 model mice.Behavioural paradigms such as forced swimming test(FST)and tail suspension test(TST)were used to detect depression-like behaviors in the mice starting on day 5 and day 36;double-labelled staining for immediate early gene protein(C-Fos)and tyrosine hydroxylase(TH)was detected in the VTA of the mice by immunofluorescence.Experiment 2:45 male C57 mice were divided into 15 mice each in the control groups,model groups and electroacupuncture groups.30 days after completion of the electroacupuncture intervention,the mice were tested for depressive behaviors using behavioural paradigms such as FST and TST;dopamine receptor D1(DRD1)and dopamine receptor D2(DRD2)was detected in the VTA of mice in each group using fluorescence quantitative PCR and Western blot techniques;the number of TH neurons in the brain area of the VTA of mice was observed by immunofluorescence.Results Experiment 1:Compared with the control group,the immobile duration of the model group increased in the TST(P<0.001)and FST(P<0.001)on day 5 and day 6,and the immobile duration of the model group increased in the TST(P<0.01)and FST(P<0.01)on day 36 and day 37;compared with the control group,the number of C-Fos and TH fluorescence double-labelled neurons in the model group increased(P<0.05).Experiment 2:At day after completion of the electroacupuncture intervention,the immobile duration of TST(P<0.01)and FST(P<0.01)were decreased in the electroacupuncture group compared with the model group;compared with the control group,DRD1 mRNA(P<0.001)and protein expression(P<0.01)were increased in the VTA of the electroacupuncture group,and DRD2 mRNA(P<0.001)and protein expression(P<0.05)were decreased,TH protein expression(P<0.05)increased,and the number of TH neurons increased(P<0.01).Conclusion Early intervention with auricular electroacupuncture points has an ameliorative effect on depression-like behaviors induced by acute stress disorder in mice,which may be achieved by modulating the activity level of dopaminergic neurons and the expression level of DRD1 and DRD2 in the VTA.

Objective:To observe the effect of electroacupuncture on depression in chronic pain mice; To explore its mechanism.Methods:36 C57BL/6J mice were divided into a blank control group, a sham-operation group, a model group, and an electroacupuncture group using a random number table method, with 9 mice in each group. The chronic compression injury model of sciatic nerve was established in the model group and electroacupuncture group. Mechanical pain threshold (MWT) and latent heat wave leg reflex (TWL) were measured on preoperative day 1 and postoperative days 4, 7, 14, 21, and 35. Electroacupuncture treatment was performed on the 14th day after modeling, and on the 35th day after modeling, open field experiments, elevated cross maze experiments, forced swimming experiments, and tail suspension experiments were conducted to evaluate depressive like behavior in mice. Western blot was used to detect the protein expressions of glutamate receptor 1 (GluA1), glutamate receptor 2 (GluA2), human glucose transporter 3 (GLUT3), and calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in the hippocampus of each group of mice; GluA1 positive cells in the hippocampus of mice was observed using immunofluorescence technology.Results:Compared with the blank group, the MWT and TWL value of the model group decreased ( P<0.05) on postoperative days 4, 7, 14, and 21. Compared with the model group, the electroacupuncture group had a longer stay time in the central area of the open field ( P<0.01), an increased percentage of stay time and activity frequency in the elevated arm opening ( P<0.01), a shorter static time for forced swimming ( P<0.01), and a shorter immobility time for the suspended tail ( P<0.01). Compared with the model group, the expressions of GluA1, GLUT3, GluA2, and CaMKⅡ proteins in the hippocampus of mice in the electroacupuncture group increased ( P<0.05), and the number of GluA1 positive cells increased ( P<0.05). Conclusion:Electroacupuncture can affect synaptic plasticity by regulating the AMPA receptor in the hippocampal region, thereby improving depressive mood caused by chronic pain.

Extensive penile ulcer secondary to granulomatosis with polyangiitis（GPA）is clinically rare. This study reports a 20-year-old male patient with pathologically confirmed GPA-induced penile ulcers. Following control of GPA progression and wound infection management，reconstruction using a scrotal pedicled flap was performed to address the penile skin defect. The follow-up of 1 year results demonstrated favorable flap survival and significant improvement in penile appearance.

Objective To evaluate the safety and effectiveness of different doses of epidural oxycodone injection for traction reaction during cesarean sections to determine the optimal dose.Methods Totally 119 cases of parturients who underwent cesarean sections from October 2023 to May 2024 were selected and randomly divided into groups A,B,C and D.All four groups of lying-in women received epidural injection after the umbilical cord was cut.Groups A,B and C were given oxycodone 3 mg,5 mg and 7 mg respectively,and group D was given an equal amount of normal saline.The primary outcomes were documentation of maternal vital signs and traction reaction during the surgery.Secondary outcomes included patient-controlled intravenous analgesia(PCIA)times within 48 hours and documentation of any postoperative adverse events within 24 hours.Results The comparison of in-tra?operative vital signs among the four groups of patients revealed no statistically significant differences.In groups A,B and C the incidence of traction reactions was significantly lower at 20％,17.2％and 3.3％,respectively,compared to group D at 53.3％,showing statistically significant differences(P<0.05).Additionally,the inci?dence of traction reaction in group C was significantly lower than in group A(P<0.05).Groups A,B and C pro?duced significantly better results than group D in terms of the duration of anesthesia.PCIA presses were substan?tially less in groups A and C than in group D(P<0.05),and group C had a significantly higher total incidence of adverse events than group A and group D(P<0.05).Conclusions Epidural injection of 3 mg,5 mg and 7 mg oxycodone has been proved to significantly reduce traction reaction during cesarean sections while minimally im?pacting intraoperative vital signs.This intervention has the potential to extend the duration of anesthesia,decrease the frequency of PCIA presses.Among these,7 mg is the most effective but has the highest incidence of adverse effects,requiring carefully post?operative monitoring.

Objective To observe the effects of electroacupuncture auricular acupuncture points on depression-like behaviors and ventral dorsal tegmental area(VTA)TH,DRD1 and DRD2 induced in well acute stress disorder(ASD)mice.Methods Experiment 1:18 male C57 mice were divided into 9 control and 9 model mice.Behavioural paradigms such as forced swimming test(FST)and tail suspension test(TST)were used to detect depression-like behaviors in the mice starting on day 5 and day 36;double-labelled staining for immediate early gene protein(C-Fos)and tyrosine hydroxylase(TH)was detected in the VTA of the mice by immunofluorescence.Experiment 2:45 male C57 mice were divided into 15 mice each in the control groups,model groups and electroacupuncture groups.30 days after completion of the electroacupuncture intervention,the mice were tested for depressive behaviors using behavioural paradigms such as FST and TST;dopamine receptor D1(DRD1)and dopamine receptor D2(DRD2)was detected in the VTA of mice in each group using fluorescence quantitative PCR and Western blot techniques;the number of TH neurons in the brain area of the VTA of mice was observed by immunofluorescence.Results Experiment 1:Compared with the control group,the immobile duration of the model group increased in the TST(P<0.001)and FST(P<0.001)on day 5 and day 6,and the immobile duration of the model group increased in the TST(P<0.01)and FST(P<0.01)on day 36 and day 37;compared with the control group,the number of C-Fos and TH fluorescence double-labelled neurons in the model group increased(P<0.05).Experiment 2:At day after completion of the electroacupuncture intervention,the immobile duration of TST(P<0.01)and FST(P<0.01)were decreased in the electroacupuncture group compared with the model group;compared with the control group,DRD1 mRNA(P<0.001)and protein expression(P<0.01)were increased in the VTA of the electroacupuncture group,and DRD2 mRNA(P<0.001)and protein expression(P<0.05)were decreased,TH protein expression(P<0.05)increased,and the number of TH neurons increased(P<0.01).Conclusion Early intervention with auricular electroacupuncture points has an ameliorative effect on depression-like behaviors induced by acute stress disorder in mice,which may be achieved by modulating the activity level of dopaminergic neurons and the expression level of DRD1 and DRD2 in the VTA.

Extensive penile ulcer secondary to granulomatosis with polyangiitis（GPA）is clinically rare. This study reports a 20-year-old male patient with pathologically confirmed GPA-induced penile ulcers. Following control of GPA progression and wound infection management，reconstruction using a scrotal pedicled flap was performed to address the penile skin defect. The follow-up of 1 year results demonstrated favorable flap survival and significant improvement in penile appearance.

Promoting the transformation and development of public hospitals into clinical research-oriented hospitals is the necessary way for China to deepen the reform of medicine and health system. In August 2019, Henan Cancer Hospital deeply combined the key elements of clinical research management with the concept of multidisciplinary collaborative governance, created an offline operating end of collaborative governance (including the front collaborative recruitment system, the middle collaborative quality management system, and the terminal collaborative transformation system), built a supporting internet plus intelligent auxiliary end (including the intelligent recruitment manager, the intelligent quality manager and the intelligent transformation manager), and built a clinical research intelligent management mode covering the trinity of subject recruitment, clinical research quality control, and innovation achievements transformation. The hospital focused on management elements such as " focusing on quality, improving efficiency, and increasing motivation" , and drove the front, middle, and terminal ends of the model to work together, to ensure the quality and efficiency of clinical research and achieve a comprehensive improvement in the hospital′s clinical research level. As of December 2023, the hospital had undertaken over 2 000 clinical research projects of various types, with a cumulative amount of clinical research conversion contracts exceeding 53 million yuan. This practice had achieved good results and could provided references for other tertiary public hospitals to promote high-quality development of clinical research.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.