Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.@*METHODS@#Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed.@*RESULTS@#BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05).@*CONCLUSION@#BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.@*UNLABELLED@#The graphical abstract is available on the website www.besjournal.com.

Research progress on the relationship between ciliary muscle and myopia / 国际眼科杂志(Guoji Yanke Zazhi)

As a key ocular structure, ciliary muscle has a major role in accommodating both eye and aqueous humor drainage. Recent studies have found that the position and shape of ciliary muscles in myopia are significantly different from those in emmetropia or hyperopia, and the differences of ciliary muscle may affect the progress of myopia by altering ocular accommodation, choroidal tension and intraocular pressure. The present evidence indicating that the thickening of posterior ciliary muscle was associated with the development of myopia, but the mechanism has not been clearly confirmed. This paper summarizes the relationship between the differences of ciliary muscle and myopia, and the possible mechanism of myopia changes affected by ciliary muscle, so as to provide reference for follow-up research.

Research progress of retinal microscopic changes after extraocular muscle surgery / 国际眼科杂志(Guoji Yanke Zazhi)

As a primary treatment for strabismus, extraocular muscle surgery can achieve the purpose of correcting the eye position, improving the appearance and reconstructing the third-level visual function. Previous studies have found that the vascular density(VD)and thickness of retina increased in the early stage after extraocular muscle surgery, where multiple mechanisms involved. In recent years, with the appearance of detection means such as optical coherence tomography angiography(OCTA), our quantitative understanding of retinal microscopic changes and their mechanisms brought about by traditional extraocular muscle surgery has become more and more profound. The increase of retinal VD in the early postoperative period may be closely related to the recovery of postoperative visual function. However, the related studies are few, and the association between microscopic changes and visual function after extraocular muscle surgery and its mechanism need to be further clarified. This article will review the microscopic changes of retina and their mechanisms after extraocular muscle surgery from multiple perspectives to improve our understanding of the relationship between the mechanism of its influence and visual function, with a view to provide references for the choice of extraocular muscle surgery scheme and related clinical research.

Chemical constituents from Paris rugosa rhizomes and their antimicrobial activities / 中国中药杂志

Paris rugosa(Melanthiaceae) only grows in Yunnan province of China at present, and its chemical constituents have not been systematically studied. In this study, nine compounds, including one new compound pariposide G(1) and eight known compounds of cerin(2), stigmast-4-en-3-one(3), β-ecdysone(4), ophiopogonin C'(5), methyl protogracillin(6), gracillin(7), parissaponin H(8), and parisyunnanoside G(9), were isolated and identified from the ethanol extract of P. rugosa rhizomes by column chromatography methods and semi-preparative high-performance liquid chromatography(HPLC). Compounds 1-9 were isolated from this plant for the first time. The antibacterial and antifungal activities of all the compounds were evaluated. The results showed that ophiopogonin C' had strong inhibitory effects on Candida albicans [MIC_(90)=(4.68±0.01) μmol·L~(-1)] and the fluconazole-resistant strain of C. albicans [MIC_(90)=(4.66±0.02) μmol·L~(-1)].

Transrectal ultrasound examination of prostate cancer guided by fusion imaging of multiparametric MRI and TRUS: avoiding unnecessary mpMRI-guided targeted biopsy / 亚洲男科学杂志(英文版)

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

Early effectiveness of a new minimally invasive plate in treatment of varus-type ankle arthritis / 中国修复重建外科杂志

OBJECTIVE@#To evaluate the early effectiveness of a new minimally invasive plate in the treatment of varus-type ankle arthritis.@*METHODS@#A clinical data of 15 patients with varus-type ankle arthritis who met the selection criteria between March 2021 and October 2021 were retrospectively analyzed. All the patients were treated with medial open-wedge supramalleolar osteotomy and fibular osteotomy. The osteotomies were fixed with the new minimally invasive plate. There were 7 males and 8 females with an average age of 49.8 years (range, 16-71 years). The causes of ankle arthritis included post-fracture deformity in 1 case, sprain in 8 cases, and acquired clubfoot in 1 case; and 5 cases were without obvious factors. The disease duration ranged from 1 to 12 years, with an average of 4.1 years. Comparisons were made between pre-operation and the last follow-up in the Takakura staging, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, foot function index (FFI), visual analogue scale (VAS) score, tibial anterior surface angle (TAS), tibial lateral surface angle (TLS), and talar tilt (TT).@*RESULTS@#All incisions healed by first intention. All patients were followed up 7-18 months (mean, 12.8 months). At last follow-up, the AOFAS ankle-hindfoot score, FFI, VAS score, and Takakura staging significantly improved when compared with the preoperative ones ( P<0.05). X-ray films showed that the osteotomy healed at 3 months after operation. At last follow-up, TAS significantly increased and TT decreased when compared with the preoperative ones ( P<0.05), and the difference in TLS between pre- and post-operation was not significant ( P>0.05). Complications included 1 case of intraoperative screw breakage and 2 cases of nerve injury of the affected foot. None of the patients complained of significant discomfort at the plate placement during follow-up, and no loosening of the internal fixator occurred. Eleven patients were very satisfied with the effeectiveness, while 4 were relatively satisfied.@*CONCLUSION@#The new minimally invasive plate for the varus-type ankle arthritis has good early effectiveness in relieving ankle pain, correcting deformity, improving limb alignment and ankle function, and reducing the incidence of postoperative incisional complications.

Targeting PDE4 as a promising therapeutic strategy in chronic ulcerative colitis through modulating mucosal homeostasis

Phosphodiesterase-4 (PDE4) functions as a catalyzing enzyme targeting hydrolyzation of intracellular cyclic adenosine monophosphate (cAMP) and inhibition of PDE4 has been proven to be a competitive strategy for dermatological and pulmonary inflammation. However, the pathological role of PDE4 and the therapeutic feasibility of PDE4 inhibitors in chronic ulcerative colitis (UC) are less clearly understood. This study introduced apremilast, a breakthrough in discovery of PDE4 inhibitors, to explore the therapeutic capacity in dextran sulfate sodium (DSS)-induced experimental murine chronic UC. In the inflamed tissues, overexpression of PDE4 isoforms and defective cAMP-mediating pathway were firstly identified in chronic UC patients. Therapeutically, inhibition of PDE4 by apremilast modulated cAMP-predominant protein kinase A (PKA)-cAMP-response element binding protein (CREB) signaling and ameliorated the clinical symptoms of chronic UC, as evidenced by improvements on mucosal ulcerations, tissue fibrosis, and inflammatory infiltrations. Consequently, apremilast maintained a normal intestinal physical and chemical barrier function and rebuilt the mucosal homeostasis by interfering with the cross-talk between human epithelial cells and immune cells. Furthermore, we found that apremilast could remap the landscape of gut microbiota and exert regulatory effects on antimicrobial responses and the function of mucus in the gut microenvironment. Taken together, the present study revealed that intervene of PDE4 provided an infusive therapeutic strategy for patients with chronic and relapsing UC.

Clinical features, genetic variations and enzyme replacement therapy in five Chinese patients with Fabry disease / 中华肾脏病杂志

Objective:To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease.Methods:A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks.Results:Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months ( P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions:The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.

Ischemic stroke in a young patient with human immunodeficiency virus infection due to middle cerebral artery dissection: a case report / 中华神经科杂志

Middle cerebral artery dissection is an uncommon cause of ischemic stroke in young adults, which is extremely rare in the case that it occurs in HIV-infected patients. This article reported a 26-year-old acute cerebral infarction patient with HIV antigen/antibody-positive who started with capsular warning syndrome and progressed to right basal ganglia cerebral infarction. The high-resolution vessel wall imaging showed the characteristic findings of middle cerebral artery dissection including "double luminal" and "intimal flap" signs. The coexistence of HIV-associated vasculopathy and hypertension with high blood pressure variability contributed to the occurrence of middle cerebral artery dissection in the patient. Combined with literature reports, this paper will further explore the relationship between HIV infection and cerebrovascular disease and the possible mechanism of middle cerebral artery dissection.

A public attitude survey on organ xenotransplantation / 中华器官移植杂志

Objective:To survey the public attitude towards xenotransplantation and examine its influencing factors.Methods:A survey form with 46 multiple-choice questions is offered. It is composed of general profiles of respondent and scale. The questionnaire is distributed online through the platform of Wenjuanxing(https: //www.wjx.cn). All adult respondents filled in anonymously online. Statistical processing included descriptive analysis, reliability and validity testing and variance and correlation analysis.Results:A total of 4 414 valid questionnaires are obtained between December 1, 2021 and January 31, 2022. Cronbach's alpha coefficient is 0.912 and the scale has decent reliability. Based upon the results of exploratory factor analysis, the items are grouped into five main factors, namely organ source, decision, psychosocial change, infection risk and other risks. If pig organs are proven feasible, the risks and prognosis are basically the same as human organs, 65.4% of the respondents definitely supported xenotransplantation. Among the respondents, individuals aged 31~50 years, male, born or resident in Chinese western region, higher education, non-medical institution practitioners, self/family members/friends have done or awaiting organ transplantation, self/partners supporting organ donation, future needs for organ transplantation, previous discussion of organ donation or organ transplantation with family/friends, blood donation, volunteer social worker, atheist or Buddhist/Christianc and hearing about xenotransplantation are more inclined to support xenotransplantation.Correlation analysis showed significant correlations among five main factors.Conclusions:Despite differences in attitudes towards xenotransplantation among different populations, overall attitude is favorable. Respondents are more concerned about their associated risks, especially psychosocial changes. The related researches should be stressed. And for different groups of people, corresponding stratified tutoring should be carried out. Strengthening clinical trials, heightening public attention and training medical staff are expected to further popularize this new technology.

Effects of plasma lipopolysaccharide changes on platelet release of vascular endothelial growth factor and thromobospondin-1 in patients with cirrhotic portal hypertension after TIPS procedure / 中华肝脏病杂志

Objective: To investigate the effects of plasma lipopolysaccharide (LPS) concentration changes on platelet release of vascular endothelial growth factor (VEGF) and thrombospondin (TSP)-1 in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Methods: 169 cases with cirrhotic portal hypertension were enrolled, of which 81 cases received TIPS treatment. LPS, VEGF, and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured. After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro, platelet PAC-1 expression rate, VEGF, and TSP-1 concentrations were detected. PAC-1 expression rate and the concentrations of LPS, VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected. The relationship between plasma LPS, VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed. Statistical analysis was performed by t-test, one-way ANOVA or Pearson's rho according to different data. Results: Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B, but the concentration of plasma VEGF was significantly lower than class A and B (P < 0.01). In vitro experiments showed that concentration of LPS, TSP-1, and platelet PAC-1 expression rate was higher in the supernatant, but the difference in the concentration of VEGF in the supernatant was not statistically significant. Portal vein pressure and platelet activation were significantly decreased (P < 0.01) in patients after TIPS procedure. Portal venous pressure, platelet activation, plasma LPS, and TSP-1 levels were significantly decreased continuously, while VEGF levels were significantly increased continuously after TIPS procedure. Plasma LPS concentration was positively correlated with TSP-1 concentration (r = 0.506, P < 0.001), and negatively correlated with VEGF concentration (r = -0.167, P = 0.010). Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration (r = -0.297, P = 0.016), and positively correlated with change range of plasma TSP-1 concentration (r = 0.145, P = 0.031) after TIPS. Conclusion: Portal venous pressure gradient, plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure, and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.

Vaginal wall prolapse in a premature infant / 中华围产医学杂志

A case of vaginal wall prolapse in a premature infant is reported. A 33 +1-week gestational age girl was admitted on 72 days due to intermittent crying, abdominal distension, and visible perineal mass. She was diagnosed with vaginal wall prolapse. No neurodevelopmental defects were found. She recovered for three months with nutritional improvement and conservative treatment in the digital reduction of the prolapsed organ. This case suggests that genital prolapse should be paid attention to when abdominal pressure increases in premature infants, especially those with malnutrition. If confirmed, the exclusion of neurodevelopmental defects is also necessary.

Artery stenosis in renal grafts from infantile donors to adult recipients / 中华器官移植杂志

Objective:To explore the clinical characteristics, causes, diagnosis and treatment of transplant renal artery stenosis after pediatric-to-adult kidney transplantation.Methods:Between July 2014 and March 2019, clinical data were retrospectively reviewed for 25 en-bloc and 27 single kidney transplant cases.Results:One en-bloc(4.0%)and two single kidney recipients(7.4%)were diagnosed as renal artery stenosis at Month 13-23 months post-transplantation.It was higher than the rate of stenosis in adult-to-adult transplant cases(1.1%)during the same period.As compared with recipients without stenosis, stenotic ones had younger pediatric donors( P<0.05)and yet similar body weight of donors as well as recipients( P>0.05). The inner diameters of stenonotic sites were(1.40-1.63)mm and predominant stenotic site was proximal renal artery rather than anastomotic site.The remaining parts of major renal arteries varied from 2.31 to 4.93 mm in diameter.It was normal in children with a corresponding age.All three cases responded well to percutaneous transluminal angioplasty and stenting. Conclusions:The cause of stenosis may be an undeveloped local artery diameter due to extensive tissue dissection around artery.Therefore cautious selections of infantile single renal graft for adult recipients and preserving surrounding tissue of renal artery assist in the prevention of graft arterial stenosis.

Fibula-preserving anterolateral approach for tibiotalocalcaneal arthrodesis: clinical and radiographic outcomes / 中华创伤骨科杂志

Objective:To evaluate the clinical and radiographic outcomes of tibiotalocalcaneal arthrodesis via the fibula-preserving anterolateral approach.Methods:From March 2018 to February 2021, 23 patients underwent tibiotalocalcaneal arthrodesis via the fibula-preserving anterolateral approach at the Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital.Of them, 15 were males and 8 females. Their average age at surgery was 54.4 years (range, from 28 to 72 years). There were 11 cases of traumatic arthritis, 2 cases of Charcot arthropathy, 6 cases of neurogenic equinovarus, 2 cases of traumatic equinovarus, and 2 cases of Kashin-Beck disease. Comparisons were made between preoperation and the last follow-up in ankle-hindfoot score of American Orthopedic Foot and Ankle Society (AOFAS), visual analogue scale (VAS), foot function index (FFI), hindfoot alignment angle (HA), hindfoot alignment distance (HD), and hindfoot alignment ratio (HR). The tibia-foot angle on lateral weight-bearing and patient satisfaction at the last follow-up and postoperative complications were documented.Results:This cohort were followed up for an average of 24.7 months (from 12 to 48 months). The AOFAS ankle-hindfoot score (78.2 ± 9.2), VAS [2.0 (0.5, 2.0)], FFI [19.0 (10.5, 35.0)], HA (2.7° ± 5.8°), HD [(0.1 ± 0.8) cm] and HR [44.2 (36.4, 59.2)%] at the last follow-up were significantly improved than the preoperative values [43.4 ± 12.7, 4.0 (4.0, 6.0), 98.0 (60.0, 127.0), 22.0° ± 14.3°, (2.2 ± 1.6) cm and 86.0 (66.3, 100.0)%] (all P<0.05). The tibia-foot angle on lateral weight-bearing was 89.0° (87.1°, 90.4°) at the last follow-up. By the Likert scale, 17 cases were very satisfied with the surgery, 4 cases satisfied and 2 cases tolerate, giving a satisfaction rate of 91.3%(21/23). Infection occurred in one case and nonunion in one. Conclusion:Tibiotalocalcaneal arthrodesis via the fibula-preserving anterolateral approach yields good mid- to short-term clinical and radiographic outcomes, showing a strong capability to correct ankle and hindfoot varus and equinus.

Epidemiological investigation of chronic lymphocytic leukemia in Hunan Province: based on the calculation of the registration and reporting system of malignant tumors in Hunan Province / 中国医师杂志

Objective:To understand the distribution and epidemiological characteristics of chronic lymphocytic leukemia (CLL) in Hunan Province.Methods:According to the audit methods and evaluation criteria specified by the National Cancer Registration Center, the registration data of CLL reported by 24 tumor registries was included. Through the research method of retrospective analysis, the selected registry data was calculated and analyzed according to the year, administrative division, urban and rural areas, gender and age.Results:A total of 104 newly diagnosed CLL patients were diagnosed in Hunan Province from 2014 to 2015, with an average annual morbidity of 0.39/100, 000. The morbidity in 2014 and 2015 was 0.39/100, 000 and 0.39/100, 000, respectively. The annual average morbidity in Zhuzhou was 0.8/100, 000, which was the highest among municipalities. The annual average morbidity in Kaifu District of Changsha was 1.65/100, 000, which was the highest among district-level administrative divisions. The morbidity of urban was higher than that of rural (Urban vs Rural, P=0.006). The male to female morbidity was 1.7∶1. The cases were mainly concentrated in the 61-70-year-old population, accounting for 33.65% of all cases (35/104). There were 64 patients died of CLL in Hunan Province from 2014 to 2015, and the average annual mortality was 0.24/100, 000. The mortality in 2014 and 2015 was 0.22/100, 000 and 0.26/100, 000, respectively. The average annual mortality in Hengyang was 0.53/100, 000, which was the highest among municipalities. The average annual mortality in Furong District of Changsha was 0.74/100, 000, which was the highest among district-level administrative divisions. The mortality of urban was higher than that of rural but with no significant difference ( P=0.006). The male to female mortality rate was 1.4∶1. The deaths were mainly concentrated in the 71-80-year-old population, accounting for 29.69% of all deaths (19/64). Conclusions:The morbidity of CLL in Hunan Province is much lower than that of European and American populations, and it mainly occurs in the elderly people. It is more common in men. The morbidity of urban is higher than that of rural and morbidity in Zhuzhou is the highest. The death of CLL patients was mainly in middle-aged and elderly population, with more males. The mortality of urban is slightly higher than that of rural and the mortality in Hengyang is the highest.

The effect of olmesartan on the antigen presentation function of rat dendritic cells / 中华急诊医学杂志

Objective:To explore the effect of Olmesartan on the antigen presenting function of dendritic cells (DCs) in rats.Methods:Bone marrow-derived dendritic cells of female Lewis rats were obtained. Bone marrow-derived dendritic cells were cultured with Olmesartan (final concentration 10 μmol/L; OLM-DCs) or equal volume of DMSO (Con-DCs). Mean fluorescence intensity (MFI) of the surface costimulatory molecule CD80, CD86 and MHCⅡ on DCs and the levels of IL-10 and TGF-β of DCs were analyzed by flow cytometry. DCs and CD4 +T lymphocytes were cocultured. T lymphocytes proliferation was analyzed by flow cytometry. IFN-γ in the supernatants were determined by ELISA. Results:The expression of MHC Ⅱ on DCs was inhibited by Olmesartan. The level of intracellular IL-10 in DCs was up-regulated by Olmesartan. Compared with Con-DCs, T lymphocytes proliferation and the level of IFN-γ were inhibited by OLM-DCs.Conclusions:Olmesartan could induce tolerogenic DCs in vitro. These tolerogenic DCs could inhibit T lymphocytes proliferation and the production of Th1 cytokine.

Nucleocytoplasmic transport and neurodegenerative diseases / 药学学报

Nucleocytoplasmic transport is the basic cellular activity of eukaryotic cells, which plays a role in cell physiological and pathological processes. A large amount of evidences indicate that impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to the pathology of neurodegenerative diseases. The regulation of nucleocytoplasmic transport is crucial to elucidate the pathogenesis and intervention in the neurodegenerative diseases. This article summarizes the evidences in disturbed nucleocytoplasmic transport of neurodegenerative diseases in the past two decades, further explores the directions and provides a theoretical basis for the pathogenesis and drug targets in neurodegenerative diseases.

Preparation and application of a PDGFRβ-targeted near-infrared fluorescent probe for molecular optical imaging of lung cancer / 中国胸心血管外科临床杂志

@#Objective    To prepare platelet-derived growth factor receptor β (PDGFRβ)-targeted near-infrared molecular probe and evaluate its potential in optical molecular imaging of lung cancer. Methods    PDGFRβ-specific affibody Z-tri was recombinantly expressed in Escherichia coli (E. coli) and purified using affinity chromatography. In vitro cell-binding of Z-tri was analyzed by flow cytometry. Cellular distribution of Z-tri in tumor grafts was determined by protein-tracing. The molecular probe CF750-Z-tri was prepared by conjugating near-infrared fluorescent dye CF750 to Z-tri. The optical images of xenografts of lung cancer were obtained by using CF750-Z-tri combined with optical imaging system. Results    PDGFRβ-specific affibody Z-tri was highly expressed in E. coli and purified to homogeneity. Z-tri could bind PDGFRβ-positive cells but not PDGFRβ-negative cells cultured in vitro. In the tumor xenografts of human lung cancer, intravenously injected Z-tri was predominantly distributed on cells overexpressing PDGFRβ. The near infrared fluorescent dye CF750 was efficiently conjugated to Z-tri. Optical images with high contrast of lung cancer xenografts were produced by using the near-infrared fluorescent probe CF750-Z-tri combined with optical imaging system. Conclusion    The near-infrared fluorescent probe CF750-Z-tri can be used for optical imaging of human lung cancer, which takes great potential in optical imaging-guided surgery of lung cancer.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.