ObjectiveTo investigate the therapeutic effect and mechanism of Xueshisanjia San against liver fibrosis by regulating PTEN-induced putative kinase （PINK1）/Parkin signaling pathway-mediated mitophagy. MethodsForty specific pathogen free （SPF）-grade male C57BL/6 mice were randomized into the control， model， silibinin （100 mg·kg^-1）， high-dose （15.16 g·kg^-1） Xueshisanjia San， and low-dose （7.58 g·kg^-1） Xueshisanjia San groups. The mouse model of liver fibrosis was constructed by intraperitoneal injection of 20% carbon tetrachloride solution. The treatment lasted for 6 weeks. Blood was collected from the abdominal aorta after intraperitoneal anesthesia， and the liver was separated. Liver pathology was examined by hematoxylin-eosin （HE） staining， Masson staining， and Sirius Red staining. Transmission electron microscopy （TEM） was employed to observe the mitochondrial morphology in the liver tissue. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， C-reactive protein （CRP）， total bilirubin （TBil）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） in the serum of mice were measured by enzyme-linked immunosorbent assay. Immunohistochemistry， immunofluorescence assay， and Western blot were employed to determine the protein levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and collagen Ⅰ， as well as mitophagy markers microtubule-associated protein 1 light chain 3 （LC3）， p62， Beclin-1， PINK1， Parkin， and translocase of outer mitochondrial membrane 20 （TOM20）. ResultsCompared with the control group， the model group exhibited elevated levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， pathological changes such destroyed structure of hepatic lobules， disarrangement of hepatic cells， and collagen accumulation， swollen， vacuolated， and fragment mitochondria， down-regulated expression of p62 and TOM20， and up-regulated expression of LC3， Beclin-1， PINK1， and Parkin （P<0.05）. Compared with the model group， all the treatment groups exhibited declined levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， alleviated pathological damage of liver tissue and mitochondrial damage， up-regulated expression of p62 and TOM20， and down-regulated expression of α-SMA， COL1A1， LC3， Beclin1， PINK1， and Parkin （P<0.05）. ConclusionXueshisanjia San may prevent excessive mitophagy and improve mitochondrial quality by inhibiting PINK1/Parkin signaling pathway， thereby alleviating liver fibrosis.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective:To examine the risk factors for neuropathic pain (NP) after a spinal cord injury (SCI).Methods:A total of 115 patients with a SCI were analyzed retrospectively. They were divided into an NP group of 53 and a non-NP group of 62 according to the occurrence of NP. Gender, age, length of stay, occupation, level of education, cause of injury, spinal fracture, degree of SCI, the injury′s plane and complications at admission (diabetes, hypertension, anemia, venous thrombosis, pressure sores, urinary tract infection or hypoproteinemia) were recorded. T-tests and chi-squared tests were used to compare those factors between the two groups, and multivariate logistic regressions were evaluated to identify the risk factors for NP.Results:Twenty-three of the 53 cases of NP (43%) had developed within 1 month of the SCI. Thirty-seven (75%) experienced pain below the plane of the SCI. The main features reported were squeezing (34%) and numbness (26%). The multivariate logistic regression showed that the occurrence of NP was most strongly related to gender (women being particularly at risk) and venous thrombosis at admission.Conclusions:Women are at particular risk of feeling NP after an SCI, and venous thrombosis is an independent risk factor. NP should be diagnosed and treated quickly to reduce the negative impact on patients′ life quality.

Objective To investigate the effect of SP600125 on the proliferation, cell cycle, apoptosis and invasion of human cervical cancer HeLa cells. Methods CCK-8 method was used to detect the proliferation of HeLa cells treated with different concentrations of SP600125 at different time points. The 20 μmol/L of SP600125 was determined for subsequent experiments. Cell proliferation ability was detected using plate clone formation assay; nuclear morphology was observed by DAPI staining; cell cycle and apoptosis were measured by flow cytometry; cell migration and invasion were detected by cell scratch and Transwell methods; the mRNA and protein levels of p53, Mad2L1 and CDC20 were measured by qRT-PCR and Western blot after SP600125 treatment at different time points. Results Compared with control group (0.1%DMSO), cells proliferative activity were reduced by 10, 20, 30, 40 and 50 μmol/L SP600125 treatment for 24h. Compared with control group, the rate of apoptosis was significantly increased in SP600125 treatment groups, and the cell proportion in G₂/M phase increased (P < 0.001), while the cell proportion in G₀/G₁ phases cells was reduced after SP600125 treatment for 24h and 48h (P < 0.001), and the clonal number, migration and invasion ability of HeLa cells also decreased significantly (P < 0.001). qRT-PCR and Western blot results showed a significant decrease in Mad2L1 mRNA and protein expression (P < 0.05) and a significant increase in p53 and CDC20 mRNA and protein expression (P < 0.01). Conclusion SP600125 can induce cell cycle arrest of cervical cancer HeLa cells in G₂/M phase by upregulating p53 and CDC20 and downregulating Mad2L1 expression, and promote cell apoptosis to inhibit cell proliferation, migration and invasion.

Objective To investigate the current situation of depression/anxiety in gravidas and to analyze the related obstetric factors.Methods A questionnaire survey was conducted among 6 923 gravidas who registered for their first prenatal examination at Obstetrics and Gynecology Hospital of Fudan University from September 2015 to September 2016.Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were completed during the survey and general obstetric conditions and medical history were reviewed.Related obstetric factors were statistically analyzed by Chi-square test and logistic regression.Results In this study,the positive rates of depression and anxiety screening were 23.15％ (1 603/6 923) and 9.56％ (659/6 893),respectively.Univariate analysis showed that maternal depression was associated with maternal age,gravidity,parity and history of adverse pregnancies (all P＜0.05),while anxiety was related to maternal age,gravidity and history of adverse pregnancies (all P＜0.05).Multivariate analysis showed that younger gravidas (＜25 years old) had higher risks of depression and anxiety than those aged between 25 and 35 (OR=2.945,95％CI:2.266-3.829;OR=1.959,95％CI:1.381-2.780;both P＜0.05).Compared to primiparas with a history of conception,the first-time pregnant women had lower risks of depression and anxiety (OR=0.732,95％CI:0.630-0.851;OR=0.630,95％CI:0.512-0.775;both P＜0.05),and the risk of anxiety in multiparas was also decreased (OR=0.748,95％CI:0.561-0.996,P＜0.05).In addition,gravidas with previous adverse pregnant outcome showed higher risks of depression and anxiety (OR=1.549,95％CI:1.123-2.137;OR=1.712,95％CI:1.138-2.577;both P＜0.05).Conclusions The positive rates of depression and anxiety are high in gravidas,especially younger or primiparas with a history of conception and those with history of adverse pregnancies.Clinicians should pay attention to any obstetric factors related to maternal depression and anxiety.

Objective To evaluate the efficacy,bleeding profile and safety of low-dose levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women of childbearing age.Methods A multi-center,open-label,single-arm clinical trial conducted at 16 centres in China enrolled 773 healthy women of childbearing age (mean age 31.6 years old,range 18 to 40 years old),who demanded contraception,from April 2006 to June 2013.All women placed LNG-IUS 8 for 3 years and then been followed up at 3,6,9,12,18,24,30,36 months.The efficacy variables including pregnancy rate and expulsion rate were analyzed using life table,while observing adverse events (AE) to evaluate the safety.The bleeding profile happened during the study was assessed using 90-day reference intervals (World Health Organization criteria).Results Eight pregnancies occurred among 773 women,resulting in a overall Pearl index of 0.42 per 100 women years.The 3-year cumulative pregnancy rate was 0.37 per 100 women years and the 3-year cumulative expulsion rate was 1.99 per 100 women years.The number of women with bleeding/spotting reduced and the bleeding/spotting days declined over time.Totally 219 AE were reported related to LNG-IUS 8 placements.The most common AE were vaginal bleeding (8.2％,63/773)and the ovarian cyst (6.2％,52/773).LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage of women with dysmenorrhea as well as the days of dysmenorrhea decreased over time.The percentage of women satisfied or very satisfied with LNG-IUS 8 was 87.2％ (622/713).Conclusion LNG-IUS 8 is highly effective and safe for Chinese healthy women of childbearing age.

OBJECTIVETo observe and summarize the morphologic features that may suggest submucosal invasive adenocarcinoma in colorectal mucosa biopsy specimens.

METHODSThe study cohort included 432 colorectal biopsy specimens were obtained from 2006 to 2012. All the cases had radical surgery. Basing on the pathologic diagnoses, the cases were divided into 366 invasive adenocarcinoma (IAC) and 66 high-grade intraepithelial neoplasms (HGIN). These two groups were compared.

RESULTSIn the IAC group, the percentage of tumor forming cribriform structures, acute angle-shaped glands, diffuse carcinoma cell proliferation was 61.2% (224/366) , 33.8% (124/366) and 7.4% (27/366) , respectively. In the HGIN group, cribriform gland structures appeared in 6.0% (4/66) of the cases, while no acute angle-shaped gland or diffuse carcinoma cell proliferation was detected. The difference of these three characteristics in the two group was statistically significant (all P < 0.01). Glandular branching was detected in 89.9% (329/366) of IAC cases and 66.7% (44/66) of HGIN cases; this difference was not significant. There was no difference in cellular atypia between the two groups. Interstitial fibrosis was detected more frequently in the IAC group (85.5%, 313/366 in IAC versus 0 in HGIN, P < 0.01). In biopsy specimens of IAC, a few cases showed neoplastic glands in close contact with large lymphatics, adipose tissue, and ganglion.

CONCLUSIONSIn colorectal biopsy specimen, the five features that suggest submucosal invasion of the neoplastic glands including the formation of cribriform structure, angular gland, diffuse carcinoma cells, interstitial fibrosis and neoplastic glands in close contact with the thick-walled vessels.

Adenocarcinoma ; pathology ; Biopsy ; Carcinoma in Situ ; pathology ; Cell Proliferation ; Diagnosis, Differential ; Humans ; Intestinal Mucosa ; pathology ; Neoplasm Invasiveness

Objective To observe and summarize the morphologic features that may suggest submucosal invasive adenocarcinoma in colorectal mucosa biopsy specimens .Methods The study cohort included 432 colorectal biopsy specimens were obtained from 2006 to 2012.All the cases had radical surgery.Basing on the pathologic diagnoses , the cases were divided into 366 invasive adenocarcinoma (IAC) and 66 high-grade intraepithelial neoplasms (HGIN).These two groups were compared.Results In the IAC group, the percentage of tumor forming cribriform structures , acute angle-shaped glands, diffuse carcinoma cell proliferation was 61.2%(224/366), 33.8%(124/366) and 7.4%(27/366), respectively.In the HGIN group, cribriform gland structures appeared in 6.0%(4/66)of the cases, while no acute angle-shaped gland or diffuse carcinoma cell proliferation was detected.The difference of these three characteristics in the two group was statistically significant ( all P<0.01 ).Glandular branching was detected in 89.9%(329/366) of IAC cases and 66.7%(44/66)of HGIN cases;this difference was not significant.There was no difference in cellular atypia between the two groups.Interstitial fibrosis was detected more frequently in the IAC group (85.5%,313/366 in IAC versus 0 in HGIN, P<0.01).In biopsy specimens of IAC , a few cases showed neoplastic glands in close contact with large lymphatics , adipose tissue , and ganglion.Conclusions In colorectal biopsy specimen , the five features that suggest submucosal invasion of the neoplastic glands including the formation of cribriform structure , angular gland , diffuse carcinoma cells , interstitial fibrosis and neoplastic glands in close contact with the thick-walled vessels.