From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

AIMTo study the chemical constituents from water extract of Radix isatidis. (Isatis indigotica Fort. ).

METHODSThe water extract was underwent absorption by D101 macroporous resin, the portion eluted by ethanol of different concentrations was isolated and purified on silica gel column repeatedly. The obtained compounds were identified and structurally elucidated by their physico-chemical properties and spectral analysis.

RESULTSFive compounds were isolated from water extract of Radix isatidis, and were partly identified separately: 3-[2'-(5'-hydroxymethyl) furyl] -1 (2H) -isoquinolinone-7-O-beta-D-glucoside (I), lariciresinol-4,4'-di-O-beta-D-glucopyranoside (II), lariciresinol-4-O-beta-D-glucopyranoside (III), 2-hydroxy-1, 4-benzenedicarboxylic acid (IV), mannitol (V).

CONCLUSIONCompound I is a new compound and compounds IV and V were isolated from the plant for the first time.

Isatis ; chemistry ; Magnetic Resonance Spectroscopy ; Plant Extracts ; analysis

To observe the efficacy and safety of apatinib in the treatment of advanced bone and soft tissue sarcoma, and to analyze the possible related factors affecting the progression-free survival (PFS) of patients. Methods: Twenty-one patients with ad-vanced bone and soft tissue sarcoma admitted to the Department of Orthopaedics, Yunnan Cancer Hospital from June 2017 to Sep-tember 2018, were treated with apatinib tablets. The main efficacy index was progression free survival (PFS), and the secondary effica-cy index was overall survival (OS). Clinical efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST) 1.1, and overall response rate (ORR), disease control rate (DCR), and safety were olserved according to the National Cancer Institute (NCI) 4.0 standard. Results: All of the 21 patients were followed up. At the last follow-up time point, March 31st, 2019, there were no CR, 2 patients (9.5%) with PR, 7 patients with SD (33.3%), and 12 patients with PD (57.1%). The ORR was 9.5%, the DCR was 42.8%, the medi-an PFS was 8 months, and the median OS was 14 months. The patient's gender, age, ECOG score, tissue source, surgery, or chemother-apy had no statistically significant effect on PFS (P>0.05). Only the history of radiotherapy before taking apatinib was a factor for pa-tients with PFS. The effect was statistically significant (P<0.05), and patients with a history of radiotherapy had a lower PFS than pa-tients without a history of radiotherapy. The adverse reactions of gradeⅢand above had hand-foot syndrome (14.3%), pneumotho-rax (14.3%) and anemia (4.8%). Conclusions: Apatinib has a certain effect for advanced bone and soft tissue sarcoma. The adverse re-actions are generally predictable, controllable and reversible. Apatinib can be a choice for patients with advanced bone and soft tissue sarcoma with good treatment adherence and no other treatment options.

Aviation ; Humans ; Physical Fitness ; Resistance Training ; Schools ; Students

Objective To observe the changes of potassium ion (K+), lactic acid (Lac) and glucose (Glu) in swine with traumatic hemorrhagic shock (THS) inside the dry-heat environment and to explore its possible mechanism. Methods A total of 40 local Landrace piglets were randomly(random number) divided equally into 4 groups: the normal temperature sham operation group (NS), the normal temperature traumatic hemorrhagic shock group (NTHS), the dry-heat sham operation group (DS group) and the dry-heat traumatic hemorrhagic shock group (DTHS). The experiment was carried out in the artifi cia climate cabin simulated the special environment of northwest of China. After exposed to their respective environment[dry-heat environment: (40.5±0.5), plus(10±2)% humidity; normal temperature environment: (25±0.5), plus(35±5)% humidity] for 3 h. Laparotomy were performed in swine of all groups, and then splenectomy and partial hepatectomy were performed only in NTHS and DTHS. The process of exsanguination from the external iliac artery was established to make the MAP reaching to 40-50 mmHg, and thus the traumatic hemorrhagic shock model of swine was successfully made. Blood samples were collected from external iliac artery at different intervals including the time just after exposure for 3 h and the successful establishment of traumatic hemorrhagic shock model (0 h) and then every 30 min after 0 h, serum levels of K+, Lac and Glu were detected. The features of varied serum K+, Lac and Glu were observed in each group. All data were statistically analyzed using One-way ANOVA and Pearson correlation analysis. Results After exposed , the level of serum K+inside the dry-heat environment was higher than that of swine inside the normal temperature group ( P<0.01), however the Glu level was lower in the swine inside dry-heat environment than that of swine inside the normal temperature ( P<0.01).The level of serum K+and Lac of DTHS group were rapidly increased from the establishment of the model to the death in about 3 h, while those of NTHS group were increased slowly. The level of K+and Lac were positively correlated in the two groups amd the correlation coeffi cient were rDTHS=0.927 (P<0.01) and rNTHS=0.539 (P<0.01),respectively. The level of Glu was progressively decrease in DTHS group, while in NTHS group, it was not noticeable. The level of K+and Glu were negatively correlated in the two group, the correlation coeffi cient were rDTHS=-0.804 (P<0.01) and rNTHS=0.420 (P<0.01),respectively. Conclusions The changes of serum K+, Lac and Glu occurred sooner and more obvious in traumatic hemorrhagic shock models inside dry heat environment (DTHS) group than those in NTHS group. The level of serum K+positively correlated with Lac, however, negatively correlated with Glu, which suggested that hyperkalemia and acidosis should be paid more attention to the treatment of traumatic hemorrhagic shock inside the dry heat environment, and the hypoglycemia should be treated at the same time.

Objective To establish the cat models of acute morphine dependence, and explore the etiopathogenesis by investigating its electrophysiology and pathology changes of its brain tissue to provide pathological and electrophysiological evidences for clinical treatment. Methods Twelve cats were randomly divided into control group (n=3) and morphine dependent group (n=9); cats in the morphine dependent group were induced by injection of morphine hydrochloride in a daily increased manner, and at the same time, cats in the control group were injected physiological saline. After the success of model making, EEG was performed on the cortex, hippocampus and nucleus accumbens in cats of the 2 groups; the changes of every encephalic region and pituitary gland were observed under light microscope and electron microscope. Results Morphine dependent cat models were successfully established. EEG indicated that physiological waves decreased and pathological waves appeared frequently in cats of the morphine dependent group as compared with those in the normal ones.Physiological examinations showed that the neuronal degeneration, organelle reduction, mitochondria swelling, chromatin margination and karyopycnosis or even nuclear necrosis occurred in the cortex of every encephalic region. Conclusion Pathological changes and brain damages will appear under EEG after long-term use of morphine, which is intimately related to neuron ultramicrostructure changes.

Adult ; Base Sequence ; Biopsy ; Chlamydia Infections ; complications ; Chlamydia trachomatis ; genetics ; isolation & purification ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphogranuloma Venereum ; etiology ; Molecular Sequence Data ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length

Objective To investigate whether the combination of 4-E9 immunomagnetic beads and epithelial adhesion mole-cules(Epacm)beads can enhance the enrichment efficiency of MCF-7,BEL-7402 and BGC-823 cells.Methods A mono-clonal antibody was prepared and ligated with magnetic bead by a biotin and a streptavidin to prepare an immunomagnetic beads.The enrichment rate of MCF-7,BEL-7402 and BGC-823 cells was detected by the combination of two kinds of immu-nomagnetic beads and two kinds of immunomagnetic beads.Results The encapsulation rate of 4-E9 immunomagnetic beads was 57.8%,and the encapsulation rate of Epcam immunomagnetic beads was 65.8%.4-E9 immunomagnetic beads on MCF-7,BGC-823 and BEL-7402 cell capture rate was(44±5.33)%,(71±11.33)% and(78.3±8.46)% respectively.Epcam immunomagnetic beads on BGC-823,BEL-7402 and MCF-7 cell capture rate was(55.5±8.67)%,(78.88±13.11)% and (84.31±6.83)% respectively.The combination of two kinds of immunomagnetic beads on BGC-823,BEL-7402 and MCF-7cell capture rate was(80.4±8.33)%,(85.125±6.77)% and(93.23±4.33)% respectively.Joint beads group compared with 4-E9 immunomagnetic beads on BGC-823,BEL-7402 and MCF-7 cell enrichment rate were statistically significant(P=0.03,0.03,0.04),and joint beads group compared with 4-E9 immunomagnetic beads on BGC-823,BEL-7402 and MCF-7 cell enrichment rate were statistically signific(P=0.04,0.03,0.04).Conclusion The combination of two kinds of immunomag-netic beads can significantly improve the enrichment efficiency of Epcam immunomagnetic beads on BEL-7402,BGC-823 and MCF-7 cells.4-E9 antibody enrichment of circulating tumor cells may have some clinical value.

AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

OBJECTIVEUp to now surgical treatment has been still the most effective treatment for esophageal cancer. However, postoperative lymph node recurrence is still a frequent event and affects long term survival considerably. The aim of this study is to compare the results of lymph node dissection via left vs. right thoracotomies and to verify whether there is any essential difference in lymphadenectomy between these two approaches.

METHODSFive hundred and fifty-nine cases with thoracic esophageal cancer were randomly selected from the database of esophageal cancer patients who underwent surgical treatment in our hospital between May 2005 and January 2011, including 282 cases through left thoracotomy and 277 cases through right thoracotomy. This series consisted of 449 males and 110 females with a mean age of 58.8 years (age range: 36 - 78 years). The pathological types were mainly squamous cell carcinoma (548 cases) and other rare types (11 cases). The data were analyzed and compared using Chi-square test. The P-value < 0.05 was considered as statistically significant. The actual 5-year survival rate was calculated based on the recent follow-up data of the patients who underwent surgery at least 5 years ago.

RESULTSThe average number of dissected lymph nodes was 23.4 via left versus 24.6 via right thoracotomies. The overall lymph node metastasis rate was 48.9% via left thoracotomy and 53.8% via right thoracotomy, and 34.8% vs. 50.5% in the chest (P < 0.001), 29.1% vs. 17.7% in the abdomen (P = 0.001). The pathologically confirmed lymph node metastasis rate was 45.9%, 44.0% and 34.9% in the upper, middle and lower segments of thoracic esophagus, respectively. The lymph node metastasis rates detected via left and right thoracotomy in the stage T1 cases were 14.7% (5/34) vs. 42.9% (12/28) (P < 0.001), and in the stage T2 cases were 35.4% (17/48) vs. 52.8% (28/53) (P = 0.007); in the station of para-thoracic esophagus were 9.6% vs. 13.4%, in the left upper mediastinum were 2.1% vs. 7.6%, and in the right upper mediastinum were 1.4% vs. 26.0%, respectively. The preliminary actual 5-year survival rate was 38.2% in the cases via left thoracotomy vs. 42.1% in those via right thoracotomy.

CONCLUSIONSThe results of this study demonstrate that lymph node dissection is more complete via right thoracotomy than via left thoracotomy, especially for the tracheoesophageal groove and para-recurrent laryngeal nerve nodes, which may eventually improve the survival of patients with esophageal cancer. Therefore, surgical treatment via right thoracotomy by Ivor-Lewis (two incisions) mode or Levis-Tanner (three incisions) mode with two-field or three-field complete lymph node dissection may become prevalent in the future.

Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; surgery ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; methods ; Lymphatic Metastasis ; Male ; Mediastinum ; pathology ; surgery ; Middle Aged ; Neoplasm Staging ; Survival Rate ; Thoracotomy ; methods