Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Due to the historical development, most of the current domestic knowledge of medicine comes from the western countries so that some western medical terms have been still used now. There are many special names for intraarticular and periarticular fracture-dislocations in orthopedics, most of which were named directly after the medical sages who first found or characterized the fractures in detail and some of which after the injury mechanisms. However, the names are often misunderstood by domestic orthopaedists who lack the knowledge of them. This article reviews such names in order to inspire innovative thinking domestic orthopaedists by the knowledge of how the fractures were discovered.

Objective To investigate the mechanism of TNF-related apoptosis-inducing ligand (TRAIL) promoting apoptosis of pancreatic cancer cells SW1990, Patu8988 and BxPC3. Methods Three kinds of pancreatic cancer cells SW1990, Patu8988 and BxPC3 were transfected with the pCA13 plasmid carrying TRAIL gene ( pCA13 TRAIL group) and the blank plasmid control ( pCA13 group) , respectively. The expression of TRAIL mRNA in transfected cells was detected by RT-PCR, and the expression of TRAIL protein was detected by Western blot. The apoptosis rate and expression of TRAIL receptor R1 and R2 were detected by flow cytometry. Apoptosis was detected by TUNEL and Hoechst double staining, and observed by electron microscopy. The expression of caspase-3 in transfected cells was detected by immunohistochemistry. Results SW1990, Patu8988 and BxPC3 cells can expresse TRAIL mRNA and protein within 24 h after transfection. The apoptotic rate at 24 h after transfection was (27. 30 ± 5. 14)％, (13. 52 ± 0. 95)％ and (31. 40 ± 8. 70)％,respectively, which was higher than that of pCA13 group [(10. 58 ± 1. 88)％,(8. 42 ± 0. 46)％ and (16.11 ±1.66)％], respectively. The expression rates of TRAIL-R1 were (61.37 ± 3.05)％,(42.10 ± 5. 11)％ and (36. 64 ± 4. 84)％, respectively, and the expression rates of TRAIL-R2 were (36. 20 ± 4. 83)％,(37. 26 ± 8. 46)％ and (24. 32 ± 3. 71)％, respectively,which were higher than those of pCA13 group except PATU8988 cells. Positivity rates of caspase-3 were ( 14. 64 ± 5. 35 )％, ( 9. 92 ± 5. 50 )％ and (16. 12 ± 6. 74)％, which were obviously higher than ( 3. 01 ± 1. 50 )％, ( 1. 75 ± 0. 50 )％ and ( 3. 79 ± 1. 58)％ in pCA13 group,and the differences were statistically significant(P<0. 05). Conclusions TRAIL could up-regulate the expression of TRAIL R1 and R2 in multiple pancreatic cancer cell lines in vitro, and thus promote cell apoptosis.

Objective Aiming at detecting Staphylococcus aureus、Pseudomonas aeruginosa and Klebsiella pneumoniae in laboratory animals,the paper provides a rapid,sensitive and simple test method.Methods According to Staphylococcus aureus nuc gene,Pseudomonas aeruginosa LasI gene,Klebsiella pneumonia PhoE gene and general 16S rRNA gene, designed specific primers;Through the optimization of multiplex PCR primer concentrations and annealing temperature, the specificity and sensitivity of detection, establishing multiplex PCR system.Application of the PCR system test specimens of artificial infections and experiment animal feces is compared with traditional test method.Results Multiplex PCR amplification of Staphylococcus aureus (153 bp), Pseudomonas aeruginosa (600 bp) with Klebsiella pneumoniae (368 bp) and general (520 bp).The multiplex sensitivity for the purpose of 10pg, specificity of detection was not detected from other pathogens.Application of establishing multiplex PCR system to detect the artificial positive samples, and detect 1 Pseudomonas aeruginosa positive case in 76 fecals.Conclusions This paper established the multiplex PCR method which has the advantages of specific,sensitive,simple and rapid, and provides a reliable way for rapid test in laboratory animals microbiology.

Objective To investigate the correlation between serum level of insulin growth factor 1 (IGF-1) and the degree of liver fibrosis in patients with chronic hepatitis C (CHC) complicated to type 2 diabetes mellitus (T2DM). Methods The cases were divided into CHC with T2DM (39 cases), CHC (96 cases), T2DM (60 cases), and healthy control (60 cases) groups. Their human data were collected and the fasting blood glucose, insulin and insulin-like growth factor-1 levels were detected, and the insulin resistance index ( HOMA-IR) wwer calculated. The serum levels of alanine transaminase ( ALT) , aspartate transaminase ( AST) , hepatitis C virus ( HCV) RNA load and HCV genotypes were detected simultaneously in patients with hepatitis C, and liver stiffness were measured ( LSM) by transient elastography ( TE) and aspartate aminotransferase-to-platelet ratio index ( APRI) score was performed. Results ⑴ There was no significant difference between CHC with T2DM group and CHC group in diabetes family history(P>0. 05), but two groups were significantly lower than that of T2DM group (P<0. 05). ⑵The levels of fasting insu-lin (FI) and HOMA-IR in CHC with T2DM group and T2DM group were significantly higher than those in the other two groups (P<0. 05), while the levels of IGF-1 in two groups were significantly lower than those in the CHC group, and were more lower than the control group (P<0. 05). ⑶Compared the serum ALT, AST and HCV RNA load between CHC with T2DM group and CHC group, there had no significant differ-ence (P>0. 05);however, the proportion of 1b genotype, LSM and APRI score of CHC with T2DM group were significantly higher than those in CHC group(P<0. 05). ⑷ The level of serum IGF-1 was negatively correlated with HOMA-IR, LSM and APRI in CHC with T2DM group (r= -0. 71, -0. 75, -0. 69, P<0. 01). Conclusions The degree of hepatic fibrosis and the damage of IGF-1 synthesis in CHC patients with T2DM were significantly higher than those in non T2DM patients, which might be related to the insulin resistance caused by 1b genotype HCV infection.

OBJECTIVETo explore the therapeutic efficacy of a modified method with splints in correction of cryptotia.

METHODSFrom Oct. 2012 to Jan. 2014, 3 cases with unilateral cryptotia were treated with the modified method with splints. The muscles attached to the periosteum of cartilage were dissected. The muscles between the ear and temper were cut off. Then one silicon tube was put around the ear through cranioauricular sulcus. The other tube was placed within the cavum conchae and fixed with the tube around the ear.

RESULTSNo flap necrosis happened. The patients were followed up for six months to one year with satisfied and stable results.

CONCLUSIONSThe modified method is easy to perform with less morbidity. It is one of the ideal correction for cryptotia.

Ear Auricle ; abnormalities ; surgery ; Ear Cartilage ; abnormalities ; surgery ; Humans ; Reconstructive Surgical Procedures ; instrumentation ; methods ; Splints

Objective To investigate the safety and feasibility of minimally invasive stealth lateral release operation in the treatment of chronic anal fissure . Methods Clinical data of 42 patients with chronic anal fissure who underwent minimally invasive stealth lateral release from May 2012 to May 2014 was analyzed retrospectively .We use the homemade fine steel wire to pierce into the sphincter ditch with a distance from the anus of 1 cm, and put the steel wire out above the dentate line .Then the wire was took out from the other edge under the skin through the needle of bobbin .After the needle was fixed by an assistant , the free end of the steel wire was pulled quickly to cut the internal sphincter tissue instantly . Results All the 42 patients were successfully treated and discharged without complications .The recovery time was in 7 -14 d, with an average of 9 d.The healing standards included disappeared symptoms and totally healed wound .All the patients were followed up for 3-6 months, with an average of 4 months.No recurrence was found . Conclusion Minimally invasive stealth lateral release in the treatment of chronic anal fissure is safe and feasible, with many advantages such as simple performance , reliable curative effect, fast recovery time, and less postoperative complications .

Objective To investigate the methods and the therapeutic effects of groin flap and stylus recurrent branch of radial artery flap for the repair of severely contracture of the first web space. Methods From March 2007 to six 2009,45 patients with severely contracture of the first web space received treatment of groin flaps and stylus recurrent branch of radial artery flaps, with 6 to 12 months clinical observation. Among then, 33 patients received treatment of groin flaps, 12 patients received treatment of stylus recurrent branch of radial artery flaps, and 28 patients received the first web space widening as well as functional reconstruction of thumb abduction. Results Most of the flaps healed by first intention but also with distal necrosis for 3 stylus recurrent branch of radial artery flaps and 1 groin flap. And the weth of the first web space of all patients were more than 90% of comparison. From clinical observation,function of opposition recovered well. While some groinflaps got a litte fat and clumsy .The color of most flaps was as similar as normal besides, some groin flaps occurrenced pigmentation. Conclusion Children and adults below 50 yesrs should choose the groin flap, and aged people and adults more than 50yesrs shuould choose the stylus recurrent branch of radial artery flap firstly.