BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

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.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Natural antimicrobial peptides (AMPs) are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens. They have found extensive applications in the fields of medicine, food, and agriculture. However, efficiently screening AMPs from natural sources poses several challenges, including low efficiency and high antibiotic resistance. This review focuses on the action mechanisms of AMPs, both through membrane and non-membrane routes. We thoroughly examine various highly efficient AMP screening methods, including whole-bacterial adsorption binding, cell membrane chromatography (CMC), phospholipid membrane chromatography binding, membrane-mediated capillary electrophoresis (CE), colorimetric assays, thin layer chromatography (TLC), fluorescence-based screening, genetic sequencing-based analysis, computational mining of AMP databases, and virtual screening methods. Additionally, we discuss potential developmental applications for enhancing the efficiency of AMP discovery. This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

Hepatitis B virus (HBV) infection represents a significant global health challenge. Current therapeutic options, such as interferon and nucleoside analogues (NAs), are limited by issues including long-term medication toxicity, the virus's propensity to develop drug resistance, and the inability to eradicate covalently closed circular DNA (cccDNA). Core protein allosteric modulators (CpAMs), as an emerging class of anti-HBV drugs, target HBcAg to interfere with capsid assembly. This not only blocks viral nucleocapsid formation and inhibits viral replication but also indirectly destabilizes the cccDNA pool, while exhibiting a relatively high genetic barrier to resistance. This article systematically evaluates HBV drug resistance to CpAMs and proposes anti-resistance strategies, including the combination of nucleoside analogues with CpAMs, enhancing protein-drug interactions, targeting HBcAg degradation, designing multi-target inhibitors, and employing combination therapy. Looking ahead, the integration of structural biology, computational chemistry, and immunotherapy will offer innovative approaches for developing novel, highly effective, and low-resistance inhibitors, thereby advancing the functional cure of hepatitis B.

Objective:To classify the etiology of secondary hemophagocytic syndrome (sHLH) and explore its clinical, laboratory and therapeutic characteristics in order to deepen the understanding of the disease.Method:A retrospective observational study was conducted on sHLH patients who were treated at Peking University People's Hospital from January 2016 to December 2021. Patients under the age of 18 and those with missing clinical data were excluded. The distribution of departments visited and etiologies of sHLH were analyzed. Baseline data, clinical characteristics, complications, laboratory data, treatment, and in-hospital outcomes of sHLH were collected. The sHLH patients were then divided into 3 groups including malignancy group, macrophage activation syndrome (MAS) group and other etiologies (mainly infection) group. Intergroup comparisons were performed using chi-square tests, analysis of variance, Mann-Whitney tests, and other statistical methods.Results:A total 169 patients were enrolled, among these patients, 27.8% were malignancy-related HLH, 47.9% were MAS, and 24.3% were other etiologies related HLH. Statistical analysis revealed that the clinical characteristics of other etiological group was highly consistent with the malignancy group, including more and severer peripheral blood cell reduction, higher sCD25 levels, more Epstein-Barr virus infection, and the prognosis was similar, both were with more than 50% in-hospital mortality. And the incidence of hemophagocytosis was highest in other etiological groups (65.9%). In contrast, MAS group was with an obviously lower mortality of 17.3% ( P<0.05). Meanwhile, treatments including methylprednisolone pulse, cyclosporine A and interleukin-2 were used frequently in MAS group. Conclusion:Malignancy related HLH and other etiologies related HLH exhibit more similar clinical characteristics and prognosis, while the MAS group, has a milder overall condition and better prognosis.

Purpose To investigate the clinicopathological features,treatment,prognosis and differential diagnosis of plas-mablastic lymphoma(PBL).Methods Collect clinical data of 9 cases of PBL,use HE and immunohistochemistry EnVision staining,detect EB virus using in situ hybridization,detect B lymphocyte gene rearrangement using PCR,analyze its clinical and pathological characteristics,and review relevant literature.Results Among the 9 patients,there were 7 males and 2 fe-males,with a median age of 54 years.Two cases were found in the nasal cavity and sinuses,two cases in the lymph nodes,one cases in the gum,one cases in the tonsil,one cases in the skin,one in the colon and one in the anal canal.Among the 9 cases,4 were HIV positive.The skin lesions are plasma like cells,and the remaining areas are plasma like/immune like cells.Immuno-phenotype:CD138,MUM1 and C-myc were all positive.CD20,CD3 and CD5 were negative.Some of them expressed CD38(7/8),CD79a(6/9),CD56(3/7)and PAX5(1/8).Ki67 prolif-eration index was high(70％-95％).EBER in situ hybridiza-tion was positive in 8 cases.Conclusion The diagnosis of PBL is difficult and requires a combination of clinical manifestations,histological features,immunophenotype,and molecular patholo-gy to make the final diagnosis.The prognosis of PBL is very poor and there are no effective treatment options.

Objective:To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression.Methods:The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected.Results:The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive ( P<0.001), Ki-67 index below 35% ( P<0.001), well or moderate differentiation ( P<0.001) and over the age of 50 ( P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions:The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.

Objective:To investigate the clinical effects of combined tissue flap transplantation in repairing giant chest wall defects.Methods:This study was a retrospective observational study. From August 2013 to December 2020, 31 patients with chest wall tumor or radiation ulcer after radical resection of chest wall tumor and conformed to the inclusion criteria were admitted to the Department of Breast Oncoplastic Surgery of Hunan Cancer Hospital, including 12 males and 19 females, aged 25-71 years. After resection of tumor or ulcer and wound debridement, the area of secondary chest wall defect was 300-600 cm 2 with length of 16-35 cm and width of 16-32 cm. According to the actual situation of the patients and the preoperative design, the chest wall defects were repaired with the flexible combination of perforator flaps and myocutaneous flaps from different donor sites, and the area of the combined tissue flap was 260-540 cm 2 with length of 20-30 cm and width of 13-20 cm. Free posteromedial thigh perforator flap+free anterolateral thigh myocutaneous flap were used in 2 patients, free deep inferior epigastric artery perforator flap+free anterolateral thigh myocutaneous flap were used in 5 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+free anterolateral thigh myocutaneous flap were used in 7 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+pedicled latissimus dorsi myocutaneous flap were used in 2 patients, and bilateral free anterolateral thigh myocutaneous flaps were used in 15 patients. For the remaining small area of superficial tissue defect after being repaired by combined tissue flaps, skin graft was used to repair or delayed local flap transfering was performed after the tissue flaps survived and edema subsided. The appropriate blood vessels in the donor and recipient sites were selected for anastomosis to reconstruct the blood supply of tissue flaps. The wounds in the donor sites of tissue flaps that can be directly sutured were sutured directly; for those that cannot be sutured directly, the skin grafting or delayed suture was performed. The anastomosis of blood vessels in the recipient sites, operation length, and postoperative hospital stay were recorded. The survivals of tissue flaps and skin grafts, the shape and texture of reconstructed chest wall, the wound healing, scar formation, and function of donor sites of tissue flaps, and the scar formation of the donor sites of skin grafts were observed after operation. Tumor recurrence and death of recurrent patients were followed up after operation. Results:The blood vessels in the recipient sites were anastomosed as follows: proximal internal thoracic vessels for 24 times, distal internal thoracic vessels for 12 times, trunk of thoracodorsal vessels for 4 times, anterior serratus branches of thoracodorsal vessels for 8 times, and thoracoacromial vessels for 12 times. The operation length was 6.0 to 8.5 hours, and the postoperative hospital stay was 9 to 21 days. Necrosis at the edge of partial tissue flaps occurred in 4 patients after operation, which healed after dressing change, and the tissue flaps and skin grafts of the other patients survived completely. The shape and texture of the reconstructed chest wall were good. Four patients had poor wound healing in the donor sites of abdominal tissue flaps, which healed after dressing change and local drainage. Only linear scar was left in the donor sites of all tissue flaps, and there was no obvious dysfunction in the donor sites of tissue flaps. Mild hypertrophic scar was left in the donor sites of skin grafts. During follow-up of 9 to 36 months after operation, 6 patients had tumor recurrence, and the recurrence time was 5 to 20 months after operation. After comprehensive treatment for patients with tumor recurrence, 3 patients died.Conclusions:Transplantation of combined tissue flaps in repairing the giant chest wall defects can shorten the time of total operation and hospital stay, and avoid multiple operations. After operation, patients had good chest wall appearance, with reduced tumor recurrence in patients with chest wall tumor.