Objective To investigate the clinical efficacy of Bushen Jianpi Recipe(mainly composed of Astragali Radix,Epimedii Folium,Dioscoreae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Cervi Cornus Colla,Astragali Complanati Semen,Polygoni Multiflori Radix Preparata,Polygonati Rhizoma,Puerariae Lobatae Radix,and Rhei Radix et Rhizoma)on patients with type 2 diabetes mellitus(T2DM)complicated with dyslipidemia and differentiated as spleen-kidney deficiency type,and to observe its effect on the level of adiponectin(ADP).Methods Ninety patients with T2DM complicated with dyslipidemia and differentiated as spleen-kidney deficiency type were randomly divided into western medicine group,Chinese medicine(CM)group,and combination of CM and western medicine group(hereinafter referred to as combination group),and each group had 30 patients.All of the 3 groups were given conventional hypoglycemic treatment.Moreover,the western medicine group was given oral use of Atorvastatin Calcium Tablets,CM group was given Bushen Jianpi Recipe,and the combination group was given Atorvastatin Calcium Tablets together with Bushen Jianpi Recipe orally.The course of treatment lasted for 8 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,glucose and lipid metabolism indexes,fasting insulin(FINS),insulin resistance index(HOMA-IR)and serum ADP levels of the three groups were observed before and after the treatment.After treatment,the efficacy of TCM syndrome of the three groups was evaluated.Results(1)After 8 weeks of treatment,the total effective rates for TCM syndrome efficacy in the western medicine group,CM group,and combination group were 66.67%(20/30),90.00%(27/30),and 93.33%(28/30),respectively.The intergroup comparison showed that the TCM syndrome efficacy of the CM group and the combination group was significantly superior to that of the western medicine group(P＜0.05).(2)After treatment,the TCM syndrome scores in all of the three groups were decreased compared with those before treatment(P＜0.01),and the decreases of the scores in both CM group and combination group was superior to that in the western medicine group(P＜0.05 or P＜0.01).(3)After treatment,the levels of lipid metabolism parameters of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)in the three groups were improved to various degrees compared with the pre-treatment levels,of which the levels of TC,TG,and LDL-C were significantly decreased,and the level of HDL-C was significantly increased in comparison with that before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The intergroup comparison showed that the decrease of TC and LDL-C and the increase of HDL-C in the CM group were inferior to those in the western medicine group and the combination group(P＜0.05 or P＜0.01).(4)After treatment,the levels of glucose metabolism parameters of fasting plasma glucose(FPG),2-hour postprandial glucose(2hPG),glycated hemoglobin(HbA1c),FINS,and HOMA-IR in the CM group and the combination group were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),while only the levels of FPG,2hPG,and HOMA-IR in the western medicine group were decreased compared with those before treatment(P＜0.05 or P＜0.01).The intergroup comparison showed that the patients in the decrease of FPG,2hPG,HbA1c,FINS,and HOMA-IR levels in the CM group and the combination group was significantly superior to that in the western medicine group(P＜0.05 or P＜0.01).(5)In terms of adipokines,the serum ADP level in the three groups after treatment was significantly increased compared with that before treatment(P＜0.05 or P＜0.01),and the increase of serum ADP level in both CM group and combination group was significantly superior to that in the western medicine group(P＜0.05).Conclusion Bushen Jianpi Recipe has certain effect on regulating lipid metabolism,and has obvious advantages in improving clinical symptoms and insulin resistance,lowering blood glucose,and increasing ADP level in patients with T2DM complicated with dyslipidemia and differentiated as spleen-kidney deficiency type.

Cases of human infection with H7 subtype avian influenza virus(AIV)combined with five NA subtypes(N2,N3,N4,N7,and N9)have been reported.This study was aimed at establishing a method for simultaneous detection and dif-ferential diagnosis of H7 and five NA subtypes of AIV.Seven pairs of specific primers were designed according to the conserved sequences of the HA gene of H7 subtype AIV,the NA gene of five NA AIV subtypes,and the M gene of all AIV subtypes.A high-throughput GeXP typing method was established for simultaneous detection of the H7 subtype and the five NA subtypes of AIV by using GeXP multiple gene expression and capillary electrophoresis analysis technology.The specificity and sensitivity of the method were determined,and clinical samples were tested.The specificity results indicated that this method was able to simultaneously detect seven target genes in a single tube;each pair of specific primers was able to detect the corresponding AIV subtype,and the universal detection primers were able to detect all subtypes of AIV,with no cross-reaction with other common avian disease pathogens.Sensitivity results demonstrated that this method was able to simultaneously detect seven target genes with a threshold detection limit was 100 copies/μL.The detection results for 150 clinical samples were consistent with those of viral isolation and identification.The high-throughput GeXP method for simultaneous differential diagnosis of the H7 subtype and five subtypes of AIV established in this study has advantages of high specificity,high sensitivity,rapidity,and simplicity,thus providing a new detection method for the effective prevention and control of AIV.

Objective To explore and evaluate the micro-elimination mode of hepatitis C virus(HCV)in patients in a general hospital in Jiangxi Province,and provide reference for formulating provincial strategies to eliminate the public health hazards of HCV.Methods Relevant data of hospitalized patients who received HCV screening at the hospital from January 2021 to December 2022 were collected.Data from 2021 were set as the baseline and data from 2022 as the HCV micro-elimination mode operating data.Indexes such as gender,age,department,anti-HCV posi-tive rate,HCV-RNA positive rate,etc.were analyzed.The operational effect was analyzed based on specialty de-partment visiting rate,treatment rate,and loss-to-follow-up(LTFU)rate.The development of the mode was quan-titatively evaluated by superiority weakness opportunity threats-analytic hierarchy process(SWOT-AHP)method.Results A total of 397 744 hospitalized patients underwent anti-HCV screening from 2021 to 2022,with a male to female ratio of 1.34∶1 and an average age of 54 years old.The main departments for patients receiving screening were infectious diseases/gastroenterology departments.HCV gene subtypes in specimens from 62 patients was mainly subtype 1b(43 specimens),followed by subtype 6(9 specimens).The first HCV early warning rate after mode operation was 81.20％,the anti-HCV detection rate after warning was 93.15％,and the anti-HCV detection rate after subsequent pop-up window early warning was 100％.Compared with 2021,the treatment rate of HCV hospi-talized patients in 2022 has increased,with statistically significant difference(P＜0.05).However,there were no statistically significant differences in patients'specialty department visiting rate and LTFU rate(both P＞0.05).Barycentric coordinates calculation P(X,Y)=(0.018 2,0.006 9)located in the first quadrant.Conclusion The HCV micro-elimination mode for patients in a general hospital in Jiangxi Province is feasible and effective.Further mode optimization should focus on strengths/opportunities(SO)strategy,to rely on internal advantages and utilize external opportunities.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Nucleophosmin ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Leukemia, Myeloid, Acute/genetics* ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.
Male ; Female ; Mice ; Animals ; Yin Deficiency ; NLR Family, Pyrin Domain-Containing 3 Protein ; Sex Factors ; Cyclooxygenase 2 ; NF-kappa B ; Antidepressive Agents/pharmacology*

OBJECTIVE: Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy. METHODS: The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression. RESULTS: rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity. CONCLUSION Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.
Mice ; Animals ; Humans ; Melitten/genetics* ; Dependovirus/genetics* ; Serogroup ; HEK293 Cells ; Mice, Nude ; Mice, Inbred C57BL ; Transgenes ; Genetic Vectors/genetics*

Objective: To explore the effect and mechanism of lycorine on oxaliplatin ( OXA) induced chemotherapy pain in mice． Methods : 40 mice were randomly divided into 4 groups，10 mice per group，which were respectively divided into control group，model group，administration group，and inhibitor group．A mouse model of chemotherapy induced pain was established by intraperitoneal injection of OXA for 5 consecutive days．Intrathecal administration of lycorine was performed．Behavioral changes and expression levels of inflammatory related proteins were detected . Results : Compared with control group，model group mice exhibited the increased number of spontaneous flinches，decreased mechanical nociceptive threshold，decreased movement distance and latency，and up-regulated expression levels of interleukin-1 β (IL-1 β) ，astrocytic marker glial fibrillary acidic protein ( GFAP) ，cyclooxygenase-2( COX-2) ，NOD-like receptor protein 3 ( NLRP3 ) ，cysteinyl aspartate and specific proteinase 1 ( Caspase- 1) ．Compared with model group，lycorine administration reduced the number of spontaneous flinches，increased mechanical nociceptive threshold ，enhanced the movement distance and latency ，bound and reduced COX-2 expression，down-regulated the expression levels of IL-1 β , GFAP ，NLRP3 and Caspase-1． Conclusion Lycorine reduces COX-2 expression，inhibits NLRP3 inflammasome activation，suppresses spinal inflammation，consequently alleviates pain behaviors and improved motor ability of mice.

Objective: To establish an in vitro organoid model of human salivary gland basal cell adenoma (BCA). Methods: Fresh tumor sample from a 66-year-old female patient diagnosed with salivary gland BCA was collected from the Dpartment of Oral pathology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in October 2021. And the organoid culture was performed in vitro in a culture medium based on solid droplets of matrix gel, and the growth of the organoid was observed by inverted microscopy. After 14 days, the organoid was fixed in 10% neutral formalin and made into paraffin blocks by agar pre-embedding paraffin embedding method, sectioned. HE staining, morphological observation and immunohistochemical staining of p63, Ki-67, cytokeratin14 (CK14), β-catenin, S-100 and calponin were used for organoids identification. Results: The established BCA organoids were lobulated nodular locally under light microscopy, with deposition of eosinophilic glass-like material around the nests of organoid cells, similar to the morphological architectures of the parental BCA. Immunohistochemistry showed that organoids expressed CK14, p63, and β-catenin in various degree, which was consistent with the immunophenotypic characteristics of the parental BCA tumor cells. Conclusions: An in vitro culture system of BCA organoids was preliminarily established which provides a new model for the study of the pathogenesis of salivary gland tumors.
Aged ; Female ; Humans ; Adenoma/pathology* ; beta Catenin ; China ; Organoids/pathology* ; Salivary Glands ; Salivary Gland Neoplasms