DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Objective To explore the medication rules of Professor ZHONG Guang-Ling's prescriptions for the treatment of lumbar disc herniation(LDH)based on data mining method,so as to provide reference for the treatment of LDH with Chinese medicine.Methods The prescriptions for the effective cases of outpatients of LDH treated by Professor ZHONG Guang-Ling in the recent 5 years were collected.The medication frequency of Chinese medicines in the included prescriptions and the distribution of their properties,flavors and meridian tropism were investigated.Moreover,the association rule analysis and cluster analysis of the high-frequency drugs were carried out.Results A total of 164 prescriptions were included and 168 Chinese medicines were used.The top 10 high-frequency drugs in descending order were Achyranthis Bidentatae Radix,Chuanxiong Rhizoma,Pheretima,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Gentianae Macrophyllae Radix,Angelicae Sinensis Radix,Rehmanniae Radix Praeparata,Persicae Semen,Cyperi Rhizoma,and Carthami Flos.The properties of the prescribed drug were mainly warm and mild in nature,and bitter and pungent in flavor,and mainly had the meridian tropism of the liver,kidney and spleen meridians.According to the therapeutic actions,the drugs were mainly categorized as deficiency-supplementing drugs,dampness-removing and collateral-unblocking drugs,and blood-activating and stasis-removing drugs.The results of association rule analysis yielded 10 drug pairs,and cluster analysis yielded 6 core drug combinations.Conclusion For the treatment of LDH,Professor ZHONG Guang-Ling usually adopts the Chinese medicine for supplementing the deficiency and supporting healthy-qi,together with the medicines for nourishing the liver and kidney and regulating the spleen and stomach from the perspective of liver,kidney and spleen.Moreover,therapy of activating blood and removing stasis is also stressed,pathogen-eliminating medicines for removing dampness,unblocking collaterals and clearing heat are used based on syndrome differentiation,and then simultaneous application of purging and nourishing therapeutics is achieved through the utilization of purging method after supplementing method.

AIM To explore the effects and mechanism of verbascoside on adenine-induced infertility in rats.METHODS Rats randomly divided into the blank group,the model group,the positive control group(100 mg/kg Compound Xuanju Capsule)and low and high dose groups of verbascoside(50 and 100 mg/kg)were given 150 mg/kg adenine daily for 14 days to establish the rat model of infertility,except those of the blank group,followed by the 28 days corresponding gavage of the drugs.The rats had their general activities observed;their indexes levels of liver,kidney,testis and epididymis calculated;their sperms checked under the microscope;their pathological morphology of the liver,the kidney and the testis observed by HE staining;their spermatogenesis evaluated using the Johnsen scoring method;their serum levels of T,LH,FSH and GnRH detected by ELISA;and their testicular mRNA and protein expressions of mTOR,LC3B and ULK1 detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group displayed increased index level of the kidney(P＜0.05),decreased sperm count,sperm activity rate and sperm index level(P＜0.05),decreased serum levels of T and GnRH(P＜0.05),increased levels of LH and FSH(P＜0.05),obviously pathological damage of the kidney and testis,increased testicular expressions of mTOR mRNA and protein(P＜0.05),decreased expressions of LC3B and ULK1 mRNA and protein(P＜0.05),and decreased expression of p-mTOR protein(P＜0.05).Compared with the model group,the high-dose verbascoside group demonstrated decreased renal index level(P＜0.05),increased sperm count and sperm activity rate(P＜0.05),increased serum T level(P＜0.05),decreased LH and FSH levels(P＜0.05),improved pathological damage of the kidney and the testis at different levels,decreased testicular expressions of mTOR mRNA and protein(P＜0.05),increased expressions of LC3B,ULK1 mRNA and protein(P＜0.05),and increased expression of p-mTOR protein(P＜0.05).The high-dose verbascoside group displayed the same effects as those of the positive control Compound Xuanju Capsule.CONCLUSION Verbascoside can effectively improve the sperm quality,sex hormone disorder,reproductive function and pathological damage of kidney and testis in infertile rats,and its mechanism may be related to the enhanced positive regulation of autophagy and regulated hypothalamus-pituitary-testis axis disorder.

Amantadine(AMD)residue can accumulate in organisms through the food chain and cause serious harm to human body.AMD can specifically bind to AMD specific aptamer and cause its conformation to change from a random single strand to a stem-loop structure.To avoid the influence of excess nucleotides on binding of aptamer to AMD,the truncation of the AMD original aptamer J was optimized by retaining an appropriate stem-loop structure,and a new type of truncation aptamers was developed in this work.By comparing the truncated aptamer with the original aptamer,it was found that the truncated aptamer J-7 had better affinity and specificity with AMD.The detection limit of AMD was 0.11 ng/mL by using J-7 as specific recognition element and molybdenum disulfide nanosheet(MoS2Ns)as signal amplification element.The developed method base on truncated aptamer J-7 was used for detection of AMD in milk,yogurt and SD rat serum samples for the first time with recoveries of 86.6%-108.2%.This study provided a reference for truncating other long sequence aptamers and provided a more sensitive detection method for monitoring AMD residues in food.

Acetabular quadrilateral plate injury has become a hot spot and focus in the field of orthopaedic trauma and pelvic floor function in recent years.Although there are five fracture types,they are all based on fracture morphology,without considering the pulling force of ligaments,joint capsular and muscles.A perfect classification needs to describe the displace-ment of bone mass in three-dimensional space to better guide reduction and fixation.The seven incision and exposure methods are still the traditional open-eye surgery,and how to protect the criss-crossing vascular neural network and pelvic organs is still the focus.Quadrilateral defect causes dislocation of artificial hip joint,and quantitative evaluation of quadrilateral defect vol-ume and revision techniques are still a hot topic.In this paper,the viewpoints of three-dimensional network structure of acetab-ular pelvic vascular anatomy,anatomical surgical target channel and fixation anchor point of acetabular fracture reduction are proposed to design new techniques for accurate and minimally invasive surgical operations,in order to realize the requirements of rapid orthopedic rehabilitation.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Objective To investigate the plasma level of interleukin-31(IL-31)in patients with pulmonary arterial hypertension(PAH)and its clinical relevance.Methods The patients who were diagnosed as PAH in Zhongshan Hospital,Fudan University from January 1,2021 to December 30,2023(PAH group)and the healthy people in the same period(control group)were selected.The clinical data and follow-up records were collected.Plasma levels of IL-31,IL-1β,IL-6,IL-10,IL-12p70,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation test was used to evaluate the correlations between IL-31 and right cardiac catheterization parameters,echocardiography parameters and blood indices in patients with PAH.Cox proportional hazard model was used to analyze the prognostic factors of patients in PAH group.Results A total of 50 patients with PAH and 22 healthy controls were included.There was no significant difference in age,gender,body mass index and left ventricular ejection fraction between the two groups.Compared with the control group,the plasma level of IL-31 in the PAH group was significantly higher(168.82[149.14,177.26]pg/mL vs 152.76[145.58,159.41]pg/mL,P=0.001).Pearson correlation test showed that the plasma level of IL-31 in PAH patient was positively correlated with mean pulmonary artery pressure(r=0.652,P＜0.001)and pulmonary vascular resistance(r=0.651,P＜0.001),but was negatively correlated with tricuspid annular plane systolic excursion(r=-0.496,P＜0.001).Cox proportional hazard model showed that higher plasma level of IL-31 was an independent predictor of readmission for heart failure/all-cause mortality in patients with PAH(HR=1.130,95％CI 1.052-1.214,P=0.001).Conclusions Plasma level of IL-31 may be significantly increased in patients with PAH and be positively correlated with the severity of PAH,and elevated level of IL-31 is predictive of poor prognosis in PAH patients.

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

Purpose::The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique.Methods::A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD.Results::The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory.Conclusion::Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.