The origin and the course of the thoracic duct and its opening into the vein were studied in 150 cadavers including 15 fetuses and 138 infants. They are classfied into 5 types.1. The normol type of the thoracic duct begins in the abdominal cavity as a single trunk, It ascends along the right side of the aorta and empties into the venous system on the left side at the root of the neck. This type of the duct which is described in the general text book, occurred in 84.67 per cent.2. The two-trunk type of the thoracic duct begins in the abdominal cavity as two trunks and ascends along the each side of the aorta. The two trunks join together at different levels in the thorax forming a single trunk which empties into the venous system on the left side at the root of the neck. This type of the duct occurred in 10.66 per cent.3. The bifurcated-type of the thoracic duct starts in the abdominal cavity as a single trunk and passing cephalad on the right side of the aorta and divides into two branches at the level of the 6th～4th thoracic vertebra, The right branch opens into the venous svstem on the right side and the left branch opens into the venous system on the left side. This type of the duct occurred in 3.33 per cent. The type which ascends along the left side of the aorta was found.4. The right thoracic duct begins in the abdominal cavity as a single trunk and runs its entire course along the left side of the aorta. The termination opens into the right jugular venous angle. This type of the duct occurred in 0.67 per cent.5. The left thoracic duct begins in the abdominal cavity as a single trunk and ascends along the left side of the aorta. It empties into the left jugular venous angle. This type of the duct occurred in 0.67 per cent.

OBJECTIVETo study the effect of Shenfu injection (SF) treating cancer-related fatigue (CRF) of the patients with advanced carcinoma.

METHODFrom September 2005 to June 2009, 113 patients with advanced carcinoma who was treated in our department were selected, and were divided into test group and control group. The test group was treated with SF and common method, while the control group only was treated with common method. Three weeks later, CRF, hemoglobin (Hb), immune function, cardiac function and blood viscosity were compared between the two groups. Meanwhile, the correlations between CRF and the other indicators were analyzed.

RESULTThe test group was treated more effectively than the control group in some ways, such as relieving CRF, improving hemoglobin, some immune indicators, and cardiac function, and reducing blood viscosity. Moreover, CRF had negative correlation with Hb and cell-mediated immune, and had positive correlation with cardiac disfunction degree.

CONCLUSIONSF could relieve CRF of the patients with advanced carcinoma effectively by treating anemia and improving cell-mediated immune and cardiac function.

Adult ; Aged ; Aged, 80 and over ; Blood Viscosity ; drug effects ; Case-Control Studies ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Fatigue ; blood ; complications ; drug therapy ; physiopathology ; Female ; Heart ; drug effects ; physiopathology ; Hemoglobins ; metabolism ; Humans ; Injections ; Male ; Middle Aged ; Neoplasms ; complications ; pathology

Objective To investigate the effect of integrated traditional Chinese ( TCM ) and western medicine fast-track surgery ( FTS) in the perioperative management of laparoscopic cholecystectomy ( LC) .Methods One hundred and fifty patients with acute cholecysititis undergoing LC from June 2012 to January 2015, were recruited and divided randomly into 3 groups.Patients in group A (n=30) were treated with routine method in perioperative period, patients in group B ( n=60) were treated with western medicine FTS, and patients in group C (n=60) were treated with integrated TCM and western medicine FTS.The first exhaust time after operation, length of stay, times of clinic visit, symptoms, levels of IL-6, CRP and ALB, postoperative complications, readmission rate, reoperation rate, and patient satisfaction were evaluated in three groups.Results The first exhaust time after operation of group B and group C was earlier than that of group A [(25.16 ±8.36)h and (21.61 ±6.52)h vs.(36.06 ±10.88)h, P<0.05], and the first exhaust time of group C was earlier than that of group B (P<0.05).The length of stay of group B and group C were shorter than that of group A [(4.30 ±1.07)d and (3.98 ±1.16)d vs.(6.11 ±1.26)d, P<0.05].The nausea and vomiting, and abdominal distension of group C were lighter than those of group B [(0.27 ±0.08) vs.( 0.31 ±0.09); (0.35 ±0.09 ) vs.(0.40 ±0.13), respectively].There were no difference of the level of IL-6, CRP and ALB between group B and group C [(57.12 ±16.29) ng/L vs. (53.91 ±17.15) ng/L, (53.93 ±17.18) mg/L vs.(51.16 ±16.67) mg/L,(40.50 ±4.65) g/L vs. (41.01 ±4.60)g/L, respectively, all P<0.05].There was no difference among the three groups in the complication rate, readmission rate and reoperation rate(all P>0.05).Conclusion Integrated traditional Chinese and western medicine FTS in the perioperative period of LC can promote recovery, reduce symptoms and operation stress and maintain albumin level.

As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.

Animals ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drug Discovery ; Drug Evaluation, Preclinical ; Enzyme Inhibitors ; therapeutic use ; Humans ; Mice ; Molecular Structure ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; Pandemics ; Pneumonia, Viral ; drug therapy ; Pyrimidines ; biosynthesis

Objective:To investigate the prevalence, risk factors and outcomes of diastasis recti abdominis (DRA) in multiparas after the second delivery.Methods:From June 2017 to September 2019, 300 multiparas with an average age of (31.7±4.0) years (26 to 43 years) after the second delivery were recruited at 6 weeks postpartum from two hospitals in Wenzhou. There were 171 multiparas with two natural births,36 multiparas with one natural birth and one caesarean delivery, and 93 multiparas with two caesarean deliveries. The interrectus distance (IRD) was measured with palpation at 6 weeks, 6 months and 12 months after delivery. Data on age, height, weight before pregnancy and delivery, baby′s birth weight, abdominal circumference before pregnancy and delivery, fetus number, delivery mode and occupation type were collected. Strength and endurance of abdominal muscle was assessed using manual muscle testing and curl-ups, low back pain was assessed using Oswestry disability index(ODI), urinary incontinence was assessed with International Consultation on Incontinence guestionnaire-incontinentia urinae (ICIQ-UI) short form (ICIQ-SF), and quality of life was assessed using 36-item short form health survey (SF-36).Results:Prevalence of DRA was 51.7%(155/300), 39.3%(116/295) and 27.7%(80/289) 6 weeks, 6 months and 12 months after delivery, respectively. Logistic regression analysis indicated that age ( OR=1.39, 95 %CI:1.02-1.91, P=0.38), abdominal circumference ratio ( OR=2.31, 95 %CI:1.23-4.33, P=0.01), twins ( OR=11.41, 95 %CI:2.15-60.76, P<0.01), and cesarean section ( OR=1.44, 95 %CI:1.06-1.95, P=0.02) were the risk factors of DRA at 12 months after delivery. At 12 months after delivery, the multiparas with DRA had weaker strength and endurance of abdominal muscle ( Z=-3.62, P<0.01; Z=-8.91, P<0.01), more serious low back pain ( Z=-2.10, P=0.04), and lower quality of life on physical health ( t=-3.34, P<0.01) than the multiparas without DRA. No difference in prevalence and severity of urinary incontinence and quality of life on psychological health was found when comparing multiparas with and without DRA (χ 2=0.66, P=0.42; Z=-1.18, P=0.24; t=0.91, P=0.36). Conclusion:Multipara after the second delivery has great likelihood for DRA.Age, abdominal circumference ratio, twins, and cesarean section are the risk factors of DRA. DRA is related to abdominal muscle dysfunction, low back pain, and quality of life.

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC₅₀ values of 34.89 and 19.88 μmol·L^-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC₅₀ values of 32.67, 79.38, and 16.74 μmol·L^-1, respectively.
Flavonoids/chemistry* ; SARS-CoV-2 ; Rhizome ; COVID-19 ; Peptide Hydrolases ; Antiviral Agents/chemistry*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins