Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.

Purpose To investigate the clinical and patho-logical characteristics,molecular characteristics,treatments and prognosis of adenoid cystic carcinoma(AdCC)of the breast.Methods A retrospective analysis was conducted on the clini-cal pathology of 14 breast AdCC patients,and HE,immunohis-tochemistry,FISH testing,and follow-up were performed.Re-sults All cases were female,aged 43～70 years.10 cases of classic AdCC and 4 cases of solid-basal cell AdCC(SB-AdCC)were included.The tumor was composed of epithelial,myoepi-thelial and basal-like cells arranged in sieve,tubular and solid pattern with fibrous mucinous or glassy changes in the stroma.The tumor cells of SB-AdCC were moderately to severely atypical with frequent mitosis and necrosis,accompanied by ductal carci-noma in situ(DCIS).Expression of ER(1/14),PR(1/14),HER2(0/14),CK7(14/14),p63(12/14),CK5/6(14/14),CD117(13/14),MYB(9/14)was detected;Ki67 index was 13.2％and 46.1％in classic AdCC and SB-AdCC,respec-tively.The MYB rearrangement rates in classic AdCC and SB-AdCC were 55.6％(5/9)and 25％(1/4),respectively.All patients were underwent surgical resection and/or radiotherapy and chemotherapy.During the follow-up period(2-62 months),1 SB-AdCC patient died due to lung and liver metasta-sis,while the other 10 patients survived without tumors.Con-clusion SB-AdCC is more invasive than classical AdCC with lower frequency of MYB gene rearrangement,and immunohisto-chemical detection of MYB protein has potential value in assis-ting the diagnosis of SB-AdCC.

The liver is a solid organ with excellent regenerative potential. Its regenerative ability is closely related to liver disease. In-depth study of the mechanism of liver regeneration is of great significance for understanding liver biology and developing regenerative medicine. The mouse has been the most widely used animal model of liver regeneration for its technical, economic and anatomical advantages. The current mouse models of liver regeneration include partial liver resection, chemical drug injury, and genetic engineering models. In this review, we compared their advantages, shortcomings and application prospects to provide reference for future research.

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8⁺ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

Objective:To investigate the expression of PC4 and SFRS1 interacting protein 1 (PSIP1) in oral squamous cell carcinoma cells and the effects of PSIP1 silencing on the migration and invasion of oral squamous cell carcinoma cells, and to preliminarily explore its mechanism.Methods:The PSIP1 gene of oral squamous cell carcinoma cell line HN30 was silenced by RNA interference technique. HN30 cells were divided into si-NC group (transfected with siRNA-NC) and si-PSIP1 group (transfected with siRNA-PSIP1). Quantitative real-time PCR was used to detect the expression of PSIP1 mRNA. Scratch test and Transwell invasion test were used to detect the migration and invasion abilities of HN30 cells, and Western blotting was used to detect the expression levels of epithelial-mesenchymal transformation (EMT) related proteins in HN30 cells of the two groups.Results:The relative expression levels of PSIP1 of HN30 cells in the si-NC group and si-PSIP1 group were 1.00±0.00 and 0.21±0.06 respectively, with a statistically significant difference ( t=22.30, P=0.002). The scratch healing rates of the si-NC group and si-PSIP1 were (48.21±4.66)% and (42.05±11.74)% at 12 h respectively, with no statistically significant difference ( t=1.46, P=0.173), and the scratch healing rates of the two groups were (86.61±6.06)% and (67.76±3.62)% at 24 h respectively, with a statistically significant difference ( t=8.01, P<0.001). The invasion numbers of HN30 cells in the si-NC group and si-PSIP1 group were 91.00±7.05 and 23.34±4.98, and there was a statistically significantly difference ( t=19.20, P<0.001). Compared with the si-NC group, the migration and invasion abilities of HN30 cells in the si-PSIP1 group decreased significantly (all P<0.001). The expression levels of E-cadherin of the si-NC group and si-PSIP1 group were 1.06±0.02 and 1.43±0.13 respectively, with a statistically significant difference ( t=-4.94, P=0.036), and the expression levels of N-cadherin were 1.00±0.04 and 0.57±0.14 respectively, with a statistically significant difference ( t=5.03, P=0.007). Compared with the si-NC group, the expression level of E-cadherin in the si-PSIP1 group increased, while the expression level of N-cadherin decreased. Conclusion:Silencing the expression of PSIP1 can significantly inhibit the migration and invasion of HN30 cells, and the mechanism may be related to the effect of PSIP1 on the EMT pathway of oral squamous cell carcinoma.

Objective:To explore the effects of Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction on bone metabolism and inflammation response in osteoporosis patients. Methods:A total of 82 patients with osteoporosis of spleen-kidney deficiency, meeting the inclusion criteria in the hospital, were enrolled between June 2018 and October 2019. They were divided into observation group and control group by random number table method, 41 in each group. The control group was treated with oral calcium carbonate D3 tablets and alendronate sodium, while the observation group was treated with Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction on basis of control group. Both groups were treated for 6 months. Before and after treatment, scores of TCM symptoms were conducted. The bone mineral density (BMD) values of lumbar vertebra L 2-4, femoral neck and distal radius1/3 site were detected by dual-energy X-ray BMD analyzer. The levels of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and type I C-terminal cross linked peptide (CTX-I) were detected by electrochemiluminescence analyzer. The level of bone gla protein (BGP) was detected by radioimmunoassay. The levels of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were detected by full-automatic biochemical analyzer. The adverse events during treatment were observed. And clinical curative effect was evaluated. Results:The differences in response rate between observation group and control group was statistically significant [95.1% (39/41) vs. 78.0% (32/41); χ2=5.145, P=0.023]. After treatment, scores of clinical symptoms (pain in back and loin, soreness and weakness of waist and knees, limb fatigue, debilitation, dizziness and tinnitus, frequent nocturia, loose stools, poor complexion) in observation group were significantly lower than those in the control group ( t=14.268, 10.732, 20.720, 7.564, 9.055, 15.975, 10.826, 6.552, all Ps<0.001). After treatment, BMD values of lumbar vertebra L 2-4 (0.89 ± 0.06 g/cm 3vs. 0.81 ± 0.04 g/cm 3, t=7.104), femoral neck (0.80 ± 0.08 g/cm 3vs. 0.72 ± 0.06 g/cm 3, t=5.122) and distal radius 1/3 site (0.65 ± 0.12 g/cm 3vs. 0.56 ± 0.14 g/cm 3, t=3.125) in observation group were significantly greater than those in the control group ( P<0.01). After treatment, levels of serum BGP and IL-10 in observation group were significantly higher than those in the control group ( t=3.875, 3.714, P<0.01), while levels of TRACP-5b, CTX-I, IL-6, TNF-α and CRP were significantly lower than those in the control group ( t=3.169, 5.849, 9.412, 4.606, 5.430, all Ps<0.001). Conclusion:Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction can improve clinical symptoms in patients with primary osteoporosis of spleen-kidney deficiency, increase BMD, regulate bone metabolism, alleviate inflammatory response and improve clinical curative effect.

Objective To investigate the effects of hemiarthroplasty with different hip prostheses on the prognosis of unstable osteoporotic intertrochanteric fractures in elderly patients.Methods A retrospective case series study was conducted on the clinical data of 556 elderly patients with unstable osteoporotic femoral intertrochanteric fractures treated with hemiarthroplasty from January 2008 to December 2014.There were 142 males and 414 females,aged (83.1 ± 6.9) years (range,75-103 years).The T value of bone mineral density was-3.5--2.5 SD [(-2.8 ± 0.2) SD].There were 306 cases of type A2.2 and 250 cases of type A2.3 according to AO classification.There were 296 cases of cement type and 260 biological type according to prosthesis type.Operation time,blood loss,time for ambulation,Harris hip score,and incidence of perioperative major complications were used to compare the therapeutic outcomes between the two types of prostheses.Results The operation time [(75.5 ±9.2) minutes],blood loss [(992.9 ± 94.2)ml],and time for ambulation[(7.1 ± 1.8) days] in cement type group were all less than those [(86.1 ± 9.3) minutes,(1 139.5 ± 96.0) ml,and (8.6 ± 2.1) days]in biological type group,but the lung infection rate (19.9％),incidence of cardio-cerebrovascular complications (15.9％) and total death rate (7.1％) in cement type group were significantly greater than the those (13.5％,8.8％ and 1.9％) in biological type group (P ＜ 0.05).There was nosignificant difference in Harris score (73.6％ vs.82.7％) between the two groups (P ＞ 0.05).Conclusions In the treatment of unstable osteoporotic intertrochanteric fractures in elderly patients by hemiarthroplasty,the use of cement type prosthesis can reduce operation time,blood loss and bed rest time,but it will lead to significant increases of cardio-cerebrovascular complication and overall mortality.The prosthesis type has no significant effect on the improvement of hip function.

Objective To evaluate the technical method,clinical effect,safety and complication of the endovascular interventional therapy of intracranial A1 segment aneurysms of anterior cerebral artery(ACA).Methods The data of 14 cases with ruptured A1 segment aneurysms received interventional therapy were analyzed retrospectively.All patients were admitted with subarachnoid hem-orrhage (SAH)and classified by Hunt-Hess scale.There were 3 cases of Grade Ⅰ,5 cases of Grade Ⅱ,and 6 cases of Grade Ⅲ. One of fourteen patients was treated by stent implantation alone and 10 patients were treated by coiling alone.The other 3 patients were treated by stent-assisted coiling.Results All the cases were embolized successfully and cured.Angiography immediately after procedure showed Raymond Ⅰ in 1 1 patients,RaymondⅡ in 2 patients and Raymond Ⅲ in 1 patient.In one patient a coil loop was partly left in the parent artery.All of them showed excellent outcome without any serious complication except that one patient suf-fered transient left hemiparesis.Conclusion Endovascular interventional therapy is a safe,effective method in the treatment of the intracranial A1 segment ACA aneurysms.