Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

OBJECTIVE To analyze the relationship between the postoperative intervertebral space infection and the expressions of β-catenin and glycogen synthase kinase-3β(GSK-3β)in the patients with lumbar disc herniation(LDH).METHODS A total of 201 patients with LDH who received surgical procedures in Harbin Orthopedics and Traumatology Hospital from Jan.2022 to May 2024 were enrolled in the study and were divided into the infection group and the no infection group according to the status of postoperative intervertebral space infection.The distri-bution and drug resistance of pathogens isolated from the patients of the infection group were detected.The rela-tive expression levels of peripheral blood Wnt,β-catenin and GSK-3β proteins were compared between the two groups.RESULTS Among the 201 patients who received surgical procedures,21 had postoperative intervertebral space infections,with the infection rate 10.45％.Totally 26 strains of pathogens were isolated from the 21 patients in the infection group,11(42.31％)of which were gram-negative bacteria,and 15(57.69％)were gram-positive bacteria.The operation duration of the infection group was(3.46±0.89)hour,longer than(3.09±0.73)hour of the no infection group(t=2.146,P=0.033).There were significant differences in the expressions of peripheral blood β-catenin and GSK-3β proteins between the infection group and the no infection group(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the areas under the curves(AUCs)of the relative ex-pression levels of β-catenin and GSK-3β were 0.836 and 0.800,respectively;the sensitivities were 52.40％and 66.70％,respectively;the specificities were 90.56％and 93.89％,respectively;the cut-off point were 5.65 and 2.15,respectively.CONCLUSIONS The LDH patients are at high risk of postoperative intervertebral space infec-tion,the patients with the infection show the activation of Wnt/β-catenin signaling pathways and the rise of ex-pression levels of β-catenin and GSK-3β proteins.The levels of the indexes may facilitate the prediction of postop-erative intervertebral space infection in the LDH patients.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

OBJECTIVE To analyze the relationship between the postoperative intervertebral space infection and the expressions of β-catenin and glycogen synthase kinase-3β(GSK-3β)in the patients with lumbar disc herniation(LDH).METHODS A total of 201 patients with LDH who received surgical procedures in Harbin Orthopedics and Traumatology Hospital from Jan.2022 to May 2024 were enrolled in the study and were divided into the infection group and the no infection group according to the status of postoperative intervertebral space infection.The distri-bution and drug resistance of pathogens isolated from the patients of the infection group were detected.The rela-tive expression levels of peripheral blood Wnt,β-catenin and GSK-3β proteins were compared between the two groups.RESULTS Among the 201 patients who received surgical procedures,21 had postoperative intervertebral space infections,with the infection rate 10.45％.Totally 26 strains of pathogens were isolated from the 21 patients in the infection group,11(42.31％)of which were gram-negative bacteria,and 15(57.69％)were gram-positive bacteria.The operation duration of the infection group was(3.46±0.89)hour,longer than(3.09±0.73)hour of the no infection group(t=2.146,P=0.033).There were significant differences in the expressions of peripheral blood β-catenin and GSK-3β proteins between the infection group and the no infection group(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the areas under the curves(AUCs)of the relative ex-pression levels of β-catenin and GSK-3β were 0.836 and 0.800,respectively;the sensitivities were 52.40％and 66.70％,respectively;the specificities were 90.56％and 93.89％,respectively;the cut-off point were 5.65 and 2.15,respectively.CONCLUSIONS The LDH patients are at high risk of postoperative intervertebral space infec-tion,the patients with the infection show the activation of Wnt/β-catenin signaling pathways and the rise of ex-pression levels of β-catenin and GSK-3β proteins.The levels of the indexes may facilitate the prediction of postop-erative intervertebral space infection in the LDH patients.

Objective:To investigate the influence of T2DM Spleen-qi Deficiency syndrome on Ankle-Brachial Index (ABI).Methods:The clinical data of 298 patients with T2DM who were hospitalized in Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2019 to December 2021 were retrospectively analyzed. According to the diagnostic criteria of spleen-qi deficiency syndrome, the patients were divided into two groups: spleen-qi deficiency syndrome group and non-spleen-qi deficiency syndrome group. There were 142 patients in the spleen-qi deficiency syndrome group and 156 patients in the non-spleen-qi deficiency syndrome group. The differences of ABI between the two groups were compared, and the correlation between spleen-qi deficiency syndrome and clinical indicators (gender, age, body mass index, course of diabetes, history of hypertension, smoking history, fasting glucose, total cholesterol, triglyceride, platelet, hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, estimated glomerular filtration rate) and ABI in T2DM patients was analyzed.Results:The left ABI [1.09 (1.00, 1.19) vs. 1.13 (1.03, 1.22)] and the right ABI [1.09 (0.96, 1.17) vs. 1.12 (1.02, 1.20)] in T2DM spleen-qi deficiency syndrome group were significantly lower than those in non-spleen-qi deficiency group ( P<0.05).The left ABI was significantly correlated with spleen-qi deficiency syndrome ( r=0.122, P=0.035) and estimated glomerular filtration rate ( r=0.137, P=0.018), and the right ABI was significantly correlated with spleen-qi deficiency syndrome ( r=0.123, P=0.034) and PLT ( r=-0.115, P=0.047). After correcting for other confounding factors by multiple linear regression analysis, there was significantly correlation between spleen-qi deficiency syndrome and ABI. Conclusion:Compared with the non-spleen-qi deficiency syndrome group, T2DM patients in the spleen-qi deficiency group had a lower ankle-brachial index and were more likely to develop peripheral arterial disease.

Objective To develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to simultaneously detect the contents of gallic acid, syringin, phellodendrine, aesculin and rhein in the gallnut lotion. Methods An UPLC- MS/MS method was established. Separation was performed on an Agilent Poroshell 120 EC-C₁₈(2.1 mm×150 mm, 2.7 μm)with a gradient mobile phase system of 0.2% formic water-acetonitrile solution. The flow rate was 0.3 ml/min. The temperature of column was 30 ℃. The injection volume was 2 μl. The MS detection was in dynamic MRM mode. Results gallic acid, syringin, phellodendrine, aesculin and rhein were successfully separated using this method, with good linear relationship as the ranges of 153.8-15380、10.31-1031、5.265-526.5、50.70-5070、1.054-105.4 ng/ml, respectively. The precision, repeatability, stability and recovery were good. Conclusion This UPLC-MS/MS method is stable, rapid, and reproducible., It is suitable for detecting the contents of gallic acid, syringin, phellodendrine, esculetin and in the gallnut lotion.

Objective:To quantitatively assess the degree of bone resorption following cranial bone remodeling for children and adolescent congenital cranial deformity cases in Crouzon syndrome.Methods:A total of 14 congenital cranial deformity patients (mean age 7.7 years) who underwent cranial bone remodeling between Mar. 2014 and Dec. 2018 were selected from Shanghai Ninth People’s Hospital, and retrospectively reviewed. They were treated with modified monobloc osteotomy and distraction osteogenesis. Craniectomy and cranial bone remodeling were performed, and the follow-up period was one week(t1) and one year(t2). The patients were scanned by spiral CT at the two following time points. Then data were imported into Mimics to acquire the three-dimensional model of skull. Bone volume was measured with Mimics Research 18.0 after three-dimensional CT reconstruction. The resorption rate was calculated as (V t1-V t2)/V t1×100%(V t1 represented bone volume before distraction osteogenesis, V t2 represented bone volume after distraction osteogenesis), followed by statistical analysis. Results:Among the 14 patients, bone resorption occurred in 11 patients and the resorption rate after 1 year was 3.482%. There was no significant difference between bone volumes at 1 week and 1 year after surgery( t=0.851, P=0.410). Conclusions:Bone resorption following cranial bone remodeling for children and adolescents with congenital cranial deformity did exist, however, it was acceptable. Therefore, the surgical treatment of cranial remodeling and distraction osteogenesis is advisable for children and youth with congenital cranial deformities over 1 year old.

Objective:To quantitatively assess the degree of bone resorption following cranial bone remodeling for children and adolescent congenital cranial deformity cases in Crouzon syndrome.Methods:A total of 14 congenital cranial deformity patients (mean age 7.7 years) who underwent cranial bone remodeling between Mar. 2014 and Dec. 2018 were selected from Shanghai Ninth People’s Hospital, and retrospectively reviewed. They were treated with modified monobloc osteotomy and distraction osteogenesis. Craniectomy and cranial bone remodeling were performed, and the follow-up period was one week(t1) and one year(t2). The patients were scanned by spiral CT at the two following time points. Then data were imported into Mimics to acquire the three-dimensional model of skull. Bone volume was measured with Mimics Research 18.0 after three-dimensional CT reconstruction. The resorption rate was calculated as (V t1-V t2)/V t1×100%(V t1 represented bone volume before distraction osteogenesis, V t2 represented bone volume after distraction osteogenesis), followed by statistical analysis. Results:Among the 14 patients, bone resorption occurred in 11 patients and the resorption rate after 1 year was 3.482%. There was no significant difference between bone volumes at 1 week and 1 year after surgery( t=0.851, P=0.410). Conclusions:Bone resorption following cranial bone remodeling for children and adolescents with congenital cranial deformity did exist, however, it was acceptable. Therefore, the surgical treatment of cranial remodeling and distraction osteogenesis is advisable for children and youth with congenital cranial deformities over 1 year old.

OBJECTIVE: To investigate the persistent damage of learning and memory ability after the cessation of sub-chronic manganese(Mn)-exposure in rats. METHODS: Specific pathogen free weaning male SD rats were randomly divided into control group and low-, medium-and high-dose groups based on body weight, with 6 rats in each group. Rats were intraperitoneally injected with Mn chloride(MnCl_2·4 H_2O) at the concentrations of 0, 5, 10, or 20 mg/kg body weight, 5 days per week for 6 weeks and continued to be observed for 12 weeks after the cessation of Mn-exposure. During the experiment, the body mass of the rats was weighed. Learning and memory ability was evaluated by a Morris water-maze task at the 6 th weeks of Mn-exposure(cessation of Mn-exposure of week 0), the 6 th and 12 th week of the cessation of Mn-exposure. The organ coefficients of heart, liver, spleen, kidney and testicles were evaluated after the cessation of Mn-exposure on week 12. RESULTS: The body mass of the high-dose group was lower than that of the other 3 groups(P<0.05) at the 4 th and 6 th week of Mn-exposure and the 2 nd week of the cessation of Mn-exposure. There was no significant difference in body mass between the groups(P>0.05) on the 12 th week of the cessation of Mn-exposure. The escape latency of high-dose group was higher than that of the control group(P<0.05), and the number of platform crossings in the low-, medium-and high-dose groups were fewer than that in the control group(P<0.05) after the cessation of Mn-exposure. The escape latency was shorter and the numbers of platform crossings were higher on the 6 th and 12 th week of the cessation of Mn-exposure(P<0.05) when compared with that of the 6 th week of Mn-exposure rats. There was no statistical significance in the organ coefficients of heart, liver, spleen, kidney and testicles among the 4 groups at the 12 th week of the cessation of Mn-exposure in rats(P>0.05).CONCLUSION: Sub-chronic Mn exposure can impair learning and memory ability of rats, and the damage persists after the cessation of Mn-exposure.

Objective:To retrospect the treatment and clinical effect of craniometaphyseal dysplasia(CMD), and summarize the experience of cranial reconstruction and nasal deformity correction in the management of this case.Methods:From June 2004 to June 2018, three male CMD patients of Shanghai Ninth People’s Hospital who received treatment. One patient was 1 year-old child who received drug therapy. A 5 year-old boy was treated with nasal cavity expansion and orbital hypertelorism for plastic and reconstructive surgery. The 7 year-old patient received cranial reconstruction and nasal deformity correction. Moreover, surgical treatments from 1967 to 2017 in the literatures on CMD were reviewed.Results:Indicators (Ca, ATP, PTH) in the laboratory of the first child returned to normal after medication treatment, and there was no obvious abnormality in the following 2 months. Nasal cavity of the second case was enlarged and function of the nose was improved, and interorbital distance was reduced by 16-17 mm. However, cranial facial deformation was not ameliorated obviously. For the third patient, scaphocephaly deformity was significantly improved. Skull thickness decreased from 3cm to 1-2 cm, the anteroposterior diameter of the skull was shortened up to 6 cm. The immediate review of dd dimer was 4.25 mg/L, FDP was 20.6 μg/ml, which was significantly higher than preoperative tests (dd dimer 0.98 mg/L, FDP 7.24 μg/ml). Two weeks after surgery, the patient received skull debridement due to ineffective anti-infective treatment. Ten months later, the child was admitted to the hospital because of infection. CT scan showed bone resorption, and we treated him with skull debridement and cranioplasty. Following 16 months, the patient was in a stable condition without complications until now.Conclusions:Drug therapy has a potential role in CMD treatment. However, surgery is the only effective management of it, although there will be a high risk and many complications, and the patients need repeated operations.