Objective To investigate the mechanisms through which Qinggan Yipi formula(QgYp)may alleviate liver fibrosis by integrating network pharmacology with experiments.Methods The active ingredients and gene targets of QgYp,associated with liver fibrosis,were sourced from several databases,including the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),various professional chemical databases,the HERB database,the GeneCards database,and the Online Mendelian Inheritance in Man(OMIM)database.Protein-protein interaction(PPI)networks were developed using the STRING database and visualized through Cytoscape software.Furthermore,GO enrichment analysis and KEGG pathway analysis were conducted with the Metascape database,alongside molecular docking studies using the CB-DOCK 2 platform.HSC-T6 cells were used as the research model,and the MTT assay along with Western blotting were applied to evaluate cell proliferation and protein expression levels,and the expression of related proteins was also detected in the animal experiment.Results A total of 22 bioactive components and 124 gene targets were identified within the formula.Enrichment analyses revealed 896 GO entries and 123 signaling pathways,notably including the IL-7,TNF,Toll-like receptor,and NF-kappa B pathways.Molecular docking indicated that the key components of the formula exhibited a strong binding affinity with proteins involved in the TLR4/NF-κB signaling pathway.Additionally,experiments confirmed that QgYp effectively inhibited the proliferation of HSC-T6 cells induced by LPS,and the expression of α-SMA,COL-1,TLR4,IκB-α,and NF-κB p65 proteins in both HSC-T6 cells and rats with liver fibrosis decreased.Conclusion QgYp can effectively inhibit the TLR4/NF-κB signaling pathway and has a suppressive effect on the fibrosis process in hepatic stellate cells,offering a theoretical basis for its clinical application in treating liver fibrosis.

Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P＜0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P＜0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P＜0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P＜0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P＜0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P＜0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P＜0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P＜0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.

OBJECTIVE To analyze the diagnosis of latent tuberculosis infection(LTBI)in hospitalized patients of a tertiary general hospital and investigate the current status of related comorbidities.METHODS The clinical data were collected from the 14 448 hospitalized patients who received tuberculin skin test(TST)or interferon-gamma release assay(IGRA)in China-Japan Friendship Hospital from Jan.1,2022 to Dec.31,2023,and the results were assessed.RESULTS The detection rate of LTBI was 23.62％(3413/14448)among the hospitalized patients who received the tests,and the rate of definite diagnosis was only 4.22％(144/3413).88.40％(3017/3413)of the hospitalized patients with LTBI had at least one type of comorbidity,and the top 5 comorbidities were in turn as follows:high blood pressure,hyperlipidemia,diabetes mellitus,malignant tumors and rheumatic immune disea-ses;the number of comorbidities was increased with the age(x2=291.199,P＜0.001).The rheumatic immune disease(73/144,50.69％)was the most common type of comorbidity among the hospitalized patients with definite diagnosis of LTBI,and less than half of the patients(66/144,45.83％)were treated in rheumatology and immu-nology department.CONCLUSION The two-way screening of LTBI and comorbidities is the core premise for the standardized management of LTBI.

Objective To investigate the mechanisms through which Qinggan Yipi formula(QgYp)may alleviate liver fibrosis by integrating network pharmacology with experiments.Methods The active ingredients and gene targets of QgYp,associated with liver fibrosis,were sourced from several databases,including the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),various professional chemical databases,the HERB database,the GeneCards database,and the Online Mendelian Inheritance in Man(OMIM)database.Protein-protein interaction(PPI)networks were developed using the STRING database and visualized through Cytoscape software.Furthermore,GO enrichment analysis and KEGG pathway analysis were conducted with the Metascape database,alongside molecular docking studies using the CB-DOCK 2 platform.HSC-T6 cells were used as the research model,and the MTT assay along with Western blotting were applied to evaluate cell proliferation and protein expression levels,and the expression of related proteins was also detected in the animal experiment.Results A total of 22 bioactive components and 124 gene targets were identified within the formula.Enrichment analyses revealed 896 GO entries and 123 signaling pathways,notably including the IL-7,TNF,Toll-like receptor,and NF-kappa B pathways.Molecular docking indicated that the key components of the formula exhibited a strong binding affinity with proteins involved in the TLR4/NF-κB signaling pathway.Additionally,experiments confirmed that QgYp effectively inhibited the proliferation of HSC-T6 cells induced by LPS,and the expression of α-SMA,COL-1,TLR4,IκB-α,and NF-κB p65 proteins in both HSC-T6 cells and rats with liver fibrosis decreased.Conclusion QgYp can effectively inhibit the TLR4/NF-κB signaling pathway and has a suppressive effect on the fibrosis process in hepatic stellate cells,offering a theoretical basis for its clinical application in treating liver fibrosis.

OBJECTIVE To analyze the diagnosis of latent tuberculosis infection(LTBI)in hospitalized patients of a tertiary general hospital and investigate the current status of related comorbidities.METHODS The clinical data were collected from the 14 448 hospitalized patients who received tuberculin skin test(TST)or interferon-gamma release assay(IGRA)in China-Japan Friendship Hospital from Jan.1,2022 to Dec.31,2023,and the results were assessed.RESULTS The detection rate of LTBI was 23.62％(3413/14448)among the hospitalized patients who received the tests,and the rate of definite diagnosis was only 4.22％(144/3413).88.40％(3017/3413)of the hospitalized patients with LTBI had at least one type of comorbidity,and the top 5 comorbidities were in turn as follows:high blood pressure,hyperlipidemia,diabetes mellitus,malignant tumors and rheumatic immune disea-ses;the number of comorbidities was increased with the age(x2=291.199,P＜0.001).The rheumatic immune disease(73/144,50.69％)was the most common type of comorbidity among the hospitalized patients with definite diagnosis of LTBI,and less than half of the patients(66/144,45.83％)were treated in rheumatology and immu-nology department.CONCLUSION The two-way screening of LTBI and comorbidities is the core premise for the standardized management of LTBI.

OBJECTIVE To observe the clinical efficacy and effect on serum thymic stromal lymphopoietin(TSLP)levels of pa-tients with advanced liver cancer of qi deficiency and toxic stasis type by Jiawei Yupingfeng San.METHODS Using random double blind method,120 patients with advanced liver cancer of qi deficiency and toxic stasis type were randomly divided into 3 groups:Jiawei Yupingfeng San group,Yupingfeng San group,and placebo group,each consisting of 40 cases.All patients in the 3 groups were given conventional treatment such as radiotherapy,chemotherapy,interventional or targeted therapy;Jiawei Yupingfeng San group was given Jiawei Yupingfeng San granules,Yupingfeng San group was given Yupingfeng San granules,and placebo group was given placebo.The course of treatment was 2 months.The changes of Karnofsky functional status score(KPS score),TCM syndrome score,tumor size and serum TSLP level in the 3 groups were observed before and after treatment,and the correlation between the changes of tumor size and TSLP was analyzed.RESULTS After treatment,the KPS scores of Yupingfeng San group and Jiawei Yupingfeng San group were sig-nificantly increased(P<0.05,P<0.01),TCM syndrome score were decreased(P<0.01),tumor growth(P<0.05,P<0.01)was de-layed,and serum TSLP levels(P<0.05,P<0.01)were decreased.Furthermore,there was a slight positive correlation between chan-ges in tumor size and changes in TSLP(P<0.05).In terms of improving tumor size,the curative effect of Jiawei Yupingfeng San group was better than that of Yupingfeng San group(P<0.05).During the treatment period,no obvious adverse reactions were observed in the 3 groups of patients.CONCLUSION Combined with conventional treatment,Jiawei Yupingfeng San can significantly delay tumor growth in patients with advanced liver cancer of qi deficiency and toxic stasis type and improve patients'TCM syndromes and their qual-ity of survival.The therapeutic mechanism is related to reducing the expression of serum TSLP and improving the immune status of pa-tients,thereby delaying the growth of tumors.

Objective The progressive loading process of implants was simulated,and the influence of progressive loading method on peri-implant bone reconstruction was evaluated.Methods Using finite element analysis combined with the ANSYS parametric design language(APDL),the average bone density of the peri-implant regions was observed using conventional loading(control group)and progressive loading(experimental group)within six months of implant placement.The stress distributions of bone tissues in a 1 mm3 region of interest(ROI)around the implant and variations in bone density were observed.Results Within six months after implantation,the cortical bone density of the control group decreased by 0.19 g/cm3,whereas that of the experimental group decreased by 0.15 g/cm3.The trabecular bone density of each area in the experimental group increased by 0.4 g/cm3 compared with that in the control group.The bone density in the experimental group was lower than that in the control group.The increase in cancellous bone in the experimental group was higher than that in the control group.The finite element analysis revealed that the equivalent stress distribution range and maximum value of the experimental group(8.9 MPa)were significantly higher than those of the control group(6.68 MPa).Conclusions The use of the progressive loading method within six months after implantation was conducive to the distribution of stress on the bone tissues around the implant.This reduced the variation in bone density at the edge of the implant.The peri-implant bone density increased more under progressive loading than under conventional loading.The effect is superior to that of the conventional loading method.

Objective The progressive loading process of implants was simulated,and the influence of progressive loading method on peri-implant bone reconstruction was evaluated.Methods Using finite element analysis combined with the ANSYS parametric design language(APDL),the average bone density of the peri-implant regions was observed using conventional loading(control group)and progressive loading(experimental group)within six months of implant placement.The stress distributions of bone tissues in a 1 mm3 region of interest(ROI)around the implant and variations in bone density were observed.Results Within six months after implantation,the cortical bone density of the control group decreased by 0.19 g/cm3,whereas that of the experimental group decreased by 0.15 g/cm3.The trabecular bone density of each area in the experimental group increased by 0.4 g/cm3 compared with that in the control group.The bone density in the experimental group was lower than that in the control group.The increase in cancellous bone in the experimental group was higher than that in the control group.The finite element analysis revealed that the equivalent stress distribution range and maximum value of the experimental group(8.9 MPa)were significantly higher than those of the control group(6.68 MPa).Conclusions The use of the progressive loading method within six months after implantation was conducive to the distribution of stress on the bone tissues around the implant.This reduced the variation in bone density at the edge of the implant.The peri-implant bone density increased more under progressive loading than under conventional loading.The effect is superior to that of the conventional loading method.

Objective:To evaluate the efficacy and safety of modified mushroom-shaped occluder in the treatment of refractory thoracogastric-airway fistulas.Methods:From March 1, 2022 to June 30, 2023, 12 patients with refractory thoracogastric-airway fistulas underwent the placement of modified mushroom-shaped occluder at the Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University were enrolled. The baseline clinical data of patients such as gender, age, course of disease, and fistula diameter were recorded. The data of operation and follow-up, such as operation time and method, intraoperative and postoperative complications were also collected. The occlusion efficacy at 1 month and 6 months after surgery, as well as the improvement of body mass index (BMI) and scores of the short form 36 (SF-36) were analyzed. Paired t test and non-parametric test were used for statistical analysis. Results:There were 10 males and 2 females among the 12 patients. The median age was 66.5 years old (ranged from 53.0 to 69.0 years old), the median course of disease was 7.5 months (ranged from 3.0 to 39.0 months), and the diameter of fistula was (9.3±3.4) mm. The occluder placements were successful in all the 12 patients, with 6 cases intracavitary release and 6 extracavitary release. The operation time was (30.9±9.9) min and the time of occluder placement was (3.5±1.3) min. One patient had minor (<2 mL) bleeding during the operation and 2 patients reported mild foreign body sensation but tolerable after operation. All patients resumed oral feeding and nasojejunal tubes were removed before discharge. The follow-up time of 12 patients was (11.3±1.7) months. The initial effective occlusion rate was 11/12, and the complete occlusion rate was 9/12. Two patients died but neither were related to the procedure or instruments. The BMI of 12 patients at 1 month after surgery was (18.5±1.9) kg/m 2, which was higher than that before operation ((17.6±2.3) kg/m 2), the BMI at 6 months after operation was (20.3±2.5) kg/m 2, which was higher than that at 1 month after operation, and the differences were statistically significant ( t=-4.15 and -4.45, P=0.002 and 0.001). The scores of 8 domains of SF-36 including physical functioning, general health, vitality, mental health, role-physical, bodily pain, social functioning and role-emotional of 12 patients before operation, at 1 month after operation and 6 months after operation were 49.6±13.6, 63.3±13.5 and 75.4±8.6, 17.1±11.2, 33.2±14.5 and 56.0±12.2, 30.0±12.6, 45.0±13.5 and 67.5±8.7, 41.3±18.7, 52.0±15.4 and 68.0±8.2, 0.0 (0.0 to 75.0), 25.0 (0.0 to 100.0) and 50.0 (25.0 to 100.0), 87.8 (44.0 to 100.0), 90.8 (57.0 to 100.0) and 100.0 (94.0 to 100.0), 12.5 (0.0 to 50.0), 50.0 (37.5 to 75.0) and 81.3 (50.0 to 87.5), 0.0 (0.0 to 100.0), 66.7 (33.3 to 100.0) and 100.0 (33.3 to 100.0), respectively. The scores of 8 domains at 1 month after operation were all higher than those before operation, and the differences were statistically significant ( t=-5.25, -5.32, -4.87 and -2.51, Z=-2.97, -2.20, -3.11 and -3.00; all P<0.05). The scores of 8 domains at 6 months after operation were all higher than those at 1 month after operation, and the differences were statistically significant ( t=-4.34, -7.48, -7.10 and -4.64, Z=-2.49, -2.20, -2.97 and -2.07; all P<0.05). Conclusion:The clinical application of the improved mushroom-shaped occluder in the treatment of refractory thoracogastric-airway fistulas is effective and relatively safe.

Objective:To evaluate the safety and efficacy of endoscopic injection of autologous platelet rich plasma(PRP)in the treatment of refractory upper gastrointestinal fistula(RUGF).Methods:From June 1, 2022 to March 1, 2023, at the Department of Gastroenterology of the First Affiliated Hospital of Nanjing Medical University, 8 RUGF patients who received PRP treatment were enrolled. The baseline data such as gender, age, course of disease, and body mass index, etc. as well as the PRP treatment-related data such as the time of first treatment, length of hospital stay after the first treatment, and adverse events were recorded. The postoperative follow-up lasted till 6 months after the first treatment to assess fistula healing, and to record body mass index and health survey short form. Paired t-test and non-parametric test were used for statistical analysis. Results:Among the 8 RUGF patients, there were 7 males and 1 female. The median age was 58.5 years old (ranged from 27.0 to 75.0 years old), and the median duration of the disease was 14 months (ranged from 4 to 120 months). The maximum diameter of the fistula was(4.50±2.62) mm, the concentration multiple of PRP was (4.02±0.48) times. The operation time of the first endoscopic PRP treatment was (21.88±4.52) min; the median length of the first postoperative hospital stay was 2 days (ranged from 1 to 2 days), and the median total number of treatment was 4 (ranged from 1 to 5). The healing time was (2.57±1.72) months, 7 RUGF patients healed within 6 months after the first treatment, and the fistula was narrowed in 1 patient. There were no adverse events during or after the operation. After 6 months of treatment, the body mass index and the scores of 8 dimensions of the health survey short form which included physical functioning, physical role functioning, body pain, general health, vitality, social functioning, emotional role functioning and mental health were all higher than those before treatment ((20.91±2.15) kg/m 2 vs. (18.67±3.21) kg/m 2, 86.88±13.35 vs. 58.13±20.34, 100 (0 to 100) vs. 0(0 to 100), 83.06±11.74 vs. 56.94±28.86, 67.88±26.77 vs. 31.88±13.08, 81.88±13.87 vs. 46.25±24.02, 76.56±22.60 vs. 37.50±26.73, 100 (0 to 100) vs. 0 (0 to 100), 78.00±17.37 vs. 51.50±22.77), and the differences were statistically significant ( t=-3.40 and -3.87, Z=2.06, t=-3.03, -4.26, -4.73 and -6.06, Z=-2.06, t=-4.32; P=0.012, 0.006, 0.039, 0.019, 0.004, 0.002, 0.001, 0.039 and 0.003). Conclusion:Endoscopic injection of autologous PRP for the treatment of RUGF is safe and effective, and has a significant promotion effect on the healing of small (maximum diameter ≤ 6 mm) fistula.