ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To investigate the effect of visual soft lens assisted nasotracheal intubation in the treatment of dental caries in children under general anesthesia.Methods Eighty children aged 3-5 years undergoing dental caries treatment under general anesthesia in Stomatological Hospital Affiliated to Nanchang University from April 2020 to April 2023 were selected.According to the random number table method,they were divided into visual laryngoscope group and visual soft lens group,with 40 cases in each group.Children in visual laryngoscope group were used visual laryngoscope endotracheal intubation,children in visual soft lens group were used visual soft lens endotracheal intubation.The incidence of intubation complications such as cuff rupture,oral soft tissue injury and hoarseness were compared between two groups.The glottis exposure time,endotracheal intubation,endotracheal intubation success rate for the first time,heart rate(HR)and mean arterial pressure(MAP)were measured 30min before induction,immediately after induction,immediately after tracheal intubation and 3min after tracheal intubation.Results HR,MAP,tracheal intubation time,the incidence of cuff rupture and oral soft tissue injury immediately after tracheal intubation in visual soft lens group were lower than those in visual laryngoscope group(P＜0.05).Conclusion The use of visual soft lens for nasotracheal intubation in children with dental caries under general anesthesia has stable hemodynamics,short intubation time,and low incidence of intubation complications,which can be effectively applied in clinical practice.

Objective:To investigate the influencing factors of falls in patients with chemotherapy-induced peripheral neuropathy for gynecological cancer, and establish a Nomogram model based on independent influencing factors.Methods:A total of 216 patients with peripheral neuropathy who received chemotherapy for gynecological cancer in The First Affiliated Hospital of Army Military Medical University of the People′s Liberation Army from February 2021 to April 2023 were retrospectively selected, and were divided into the modeling set and the validation set according to the ratio of 7∶3 using random number table method. According to the occurrence of falls in the modeling set, the patients were divided into the fall group and the non-fall group. Independent influencing factors were obtained through univariate analysis and multivariate Logistic regression analysis, and a prediction model was constructed based on the regression analysis. A Nomogram map was drawn using R language software. Receiver operating characteristic curve (ROC) and calibration curve were used to test the prediction efficiency, and the predictive benefits were evaluated by clinical decision curve.Results:Among the 216 patients, 151 were included in the modeling set and 65 in the validation set. Among the patients in the modeling set, 53 cases were in the fall group, aged (62.89 ± 8.58) years old, and 98 cases were in the non-fall group, aged (59.48 ± 8.12) years old. Chemotherapy cycle, Neuropathy Impairment Score-Lower Limbs, Barthel index, Home Falls and Accidents Screening Tool, regular exercise habits, diabetes and depression were all independent influencing factors for falls in patients with chemotherapy-induced peripheral neuropathy of gynecologic cancer ( OR values were 0.312-3.727, all P<0.05). The area under the curve (AUC) of the established Nomogram model was 0.873, with good discriminating ability. The mean absolute error (MAE) of calibration curve was 0.048, which fitted the ideal curve, indicating that the model has good calibration performance. The AUC of the validation set was 0.873 and the MAE of calibration curve was 0.073, indicating that the model has good external prediction efficiency. Conclusions:This Nomogram model can predict falls in patients with chemotherapy-induced peripheral neuropathy of gynecological cancer and provide evidence for clinical prevention of falls.

Objective:To investigate changes and clinical significance of senescent cell proportion and senescence-associated cytokines in peripheral blood of patients with acute myeloid leukemia(AML)in different states.Methods:AML patients who were diagnosed and treated in the Second Hospital of Anhui Medical University were selected as research subjects(17 cases in newly diag-nosed group,16 cases in remission group,and 12 cases in relapse group),morphology of leukemia blasts and proportion of senescent cells in peripheral blood of patients in each group were observed by Regis and senescence specific β-galactosidase(SA-β-gal)staining,levels of senescence-associated cytokines IL-8,IL-1β,IL-6,IL-10 in peripheral blood of each group were detected by cytometric bead array(CBA),and differences and clinical significance among groups were compared.Results:Relapse group peripheral blood smear Regis staining showed that morphology of leukemia blasts increased significantly and proportion of SA-β-gal positive cells was significantly increased(P<0.01);levels of serum senescence-associated cytokines IL-8,IL-1β,IL-6 and IL-10 in relapse group were significantly increased(P<0.05);there was no correlation between serum senescence-associated cytokine levels and proportion of peripheral blood leukemia blasts(P>0.05);relapsed patients with higher IL-8 levels trend to have lower re-induction remission rates and worse overall survival after relapse(P<0.05);multivariate Cox regression analysis showed that IL-8 level was an indepen-dent risk factor for prognosis of relapsed patients(P<0.05).Conclusion:Increased proportion of senescent cells and significantly increased levels of senescence-associated cytokines IL-8,IL-1β,IL-6,IL-10 in peripheral blood of AML patients are closely related to disease recurrence,and relapsed patients with higher IL-8 level had poor prognosis.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML)patients with PTPN11 gene mutation.Methods Total 115 adult AML patients who underwent initial diagnosis,treatment,and second-generation sequencing(NGS)detecting at hospital were recruited in this study.Clinical da-ta included disease characteristics,treatment efficacy,long-term prognosis,immune cell subpopulations,and leu-kemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients with PTPN11 gene mutation.Results PTPN11 gene mutation rate in newly diagnosed adult AML was 9.57％,and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation.Compared with PTPN11 wild-type group,PTPN11 gene mutation group had a higher early mortality rate(18.18％vs 4.00％,P=0.048),a lower complete response rate(33.33％vs 67.71％,P=0.039),a higher recurrence rate(83.33％vs 42.31％,P=0.043),a shorter median overall survival time(9 months vs 20 months,P=0.026),a lower proportion of ef-fector T cells[(1.39±0.12)％vs(3.56±0.46)％,P=0.038],and a higher proportion of leukemia stem cells[(13.82±3.66)％vs(3.87±1.40)％,P=0.021].Conclusion PTPN11 gene mutation is a poor prognostic marker for AML.Those patients have a high early mortality rate,low complete remission rate,high recurrence rate,short median overall survival time,a low proportion of effector T cells,and a high proportion of leukemia stem cells.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective:To investigate the characteristics of gene mutation by using whole exome sequencing (WES) and its relationship with therapeutic efficacy in patients with acute myeloid leukemia (AML).Methods:The data of 30 patients with AML from the Second Hospital of Anhui Medical University between December 2014 and September 2019 were retrospectively analyzed; the result of WES, disease type and classification, genetic prognostic stratification and therapeutic efficacy were summarized. The mutation types and mutation frequency of AML patients stratified by the different clinical characteristics and genetic prognosis were compared.Results:Among 30 AML patients, 26 cases (86.7%) had 1 gene mutation at least. The genes with a mutation frequency more than 10.0% were NRAS, RUNX1, TET2, CEBPA, IDH2 and ASXL1. The function of the mutated genes was involved in signaling pathways, transcription factors, epigenetics, and RNA splicing and other biological functions; in terms of mutation pattern, 19 cases (63.3%) of all AML patients mainly presented combined mutations of many combinations. There were no significant differences in mutation rates among age, gender, disease type, disease classification and genetic prognosis stratification groups (all P > 0.05). Of the 8 fusion gene positive cases, 7 were mutated, the average mutation frequency was 175.0% (14/8). There were 19 mutations in 22 patients with negative fusion gene, the average mutation frequency was 213.6% (47/22), and the difference in mutation frequency between the two groups was statistically significant ( P = 0.001). Of the 14 cases of continuous remission, 11 had mutations, with average mutation frequency of 157.1% (22/14); there were 9 cases of mutations in 10 relapsed patients, and the average mutation frequency was 200.0% (20/10); mutations occurred in 5 patients with primary drug resistance, and the average mutation frequency was 300.0% (15/5); and the difference of mutation frequency among the three groups was statistically significant ( P = 0.009). Conclusions:Through WES analysis, it is found that most AML patients have complex and variable gene mutations; and the higher the gene mutation frequency is, the worse the prognosis of the disease is.

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%‍-‍50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).
Endometriosis/pathology* ; Endometrium/pathology* ; Female ; Humans ; Ki-67 Antigen/metabolism* ; Quality of Life ; Recurrence ; Telomerase/metabolism* ; Up-Regulation