Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

Volume electron microscopy (vEM) imaging technology was rapidly developed in recent years. It has been the advanced technology to solve high-resolution three-dimensional structures of biological samples. Much wonderful work has revealed the fine structure and interactions of intracellular organelles, the ultrastructure of tissues, and even the three-dimensional structure of entire small biological organisms. With the continuous improvement of resolution, scale and throughput, vEM is becoming more and more widely used in medicine, life sciences, clinical diagnostics and other fields. As a result, this technology has been rated by Nature as one of the seven most noteworthy frontier technologies to watch in 2023. However, the development and application of vEM-related technologies started late in China and need to be further promoted. We write this review to introduce all related vEM technologies, covering the development history of vEM, technology classification, sample preparation, data collection, image processing, etc., which is convenient for people in various fields to understand, learn, apply and further develop this technology.

This study focuses on the microenvironment acidification caused by metabolic abnormalities and ion balance disturbances during cardiac ischemia, which can significantly trigger drug resistance and thus limit the therapeutic effect of coronary heart disease. To address this issue, we delve into the potential role of carbonic anhydrase inhibitors in enhancing drug efficacy through pH regulation. First, we evaluated the potential of the carbonic anhydrase inhibitor acetazolamide, in combination with aspirin, in alleviating myocardial hypoxic injury in a cellular model. Through high-throughput screening techniques, we systematically analyzed the synergistic effect of this drug combination and determined the optimal ratio. Next, we modified the structure of aspirin using acetazolamide as the structural basis, aiming to create novel derivatives with stronger myocardial protective activity. Using in vitro and in vivo models of myocardial hypoxic injury, we evaluated the biological activity and therapeutic efficacy of these derived compounds in detail. Animal experiments were approved by the Animal Ethics Committee of Southeast University (Ethics No. 20240109001). The results showed that the structurally modified aspirin derivatives exhibited significant synergistic effects in alleviating myocardial hypoxic injury. This study reveals the mechanism of action of carbonic anhydrase inhibitors in the treatment of coronary heart disease and provides experimental and theoretical evidence for the development of novel coronary heart disease treatment drugs, which has important guiding significance for drug design and coronary heart disease treatment strategies.

As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

【Objective】 To explore the feasibility of en-bloc resection of bladder tumors by flexible cystoscope combined with laparoscopic instruments through urethra and to provide reference for the clinical application of this technique. 【Methods】 Self-designed and processed transurethral single-hole PORT and Olympus electronic cystoscope were used as observation mirror; Φ1.8 mm soft grasper, tissue scissors, electric hook, and ultrasonic scalpel were used as instruments; the porcine bladder was used as a model.The PORT was placed through the urethra, and the cystoscope was inserted to observe the inner wall of the bladder and the condition of the mucosa.After the lesion site was identified in the bladder cavity, the soft grasper was inserted to pull the mucosa to be removed, which was then fixed with tension at the target position to maintain a satisfactory feild of view.The surgeon held the cystoscope in the left hand, and operated the laparoscopic instruments into the bladder cavity through the PORT with the right hand.Observing with the cystoscope and lifting and pulling the mucosa with the grasper, the surgeon simulated the cutting and pushing actions to realize the en-bloc resection of the lesioned mucosa. 【Results】 The mucosa at 4 different locations were successfully resected on 2 in vitro porcine bladder models. 【Conclusion】 The in vitro experiments show that the combination of flexible electronic cystoscope and laparoscopic instruments achieves synergistic effects in en-bloc resection of bladder tumor by transurethral single-hole laparoscope without additional iatrogenic bladder injury caused by percutaneous bladder incision.This method is feasible in the treatment of bladder tumors, and has the potential of clinical application after further optimization.

Objective To analyze the economic burden due to healthcare-associated infection(HAI)in low birth weight(LBW)infants,and provide theoretical basis for formulating HAI related policies.Methods The data of LBW infants in a tertiary first-class hospital from January 2018 to December 2022 were retrospectively collected.Propensity score matching method and marginal analysis were adopted to evaluate the economic losses in LBW in-fants and hospitals due to HAI.Results A total of 1 048 LBW infants were included in analysis,124 of whom had HAI,with HAI incidence of 11.8％.A total of 109 pairs were successfully matched using the propensity score matching method.The median length of hospital stay for LBW infants in the HAI group and non-HAI group were 34.0 and 11.0 days,respectively,the length of hospital extended 23 days in LBW infants in the HAI group(P＜0.001).The median hospitalization expenses for LBW infants in HAI group and non-HAI group were 38 067.6 and 12 375.7 Yuan,respectively,the hospitalization expense for LBW infants in HAI group was 25 691.9 Yuan more than non-HAI group(P＜0.001).The major increased expenses were examination,treatment and medication fees.The total hospitalization expenses in different birth weight LBW infants in HAI group were all higher than non-HAI group,and the differences were all statistically significant(all P＜0.05).LBW infants with gestational age＜32 weeks had longer length of hospital stay and higher total hospitalization expense,differences were all statistically significant(all P＜0.05).When the marginal profit ratios were 5％,10％,and 15％,respectively,the economic losses caused by HAI were 371 000 Yuan,742 000 Yuan,and 1 114 000 Yuan,respectively;The ratios of loss-profit and loss-profit to infection coefficient were 0.33 and 2.79,respectively.Conclusion HAI cause significant economic losses to both LBW infants and hospitals.Infants with a birth weight ≤1 000 g and those with a gestational age＜32 weeks are key populations for prevention and control.The lost-profit to infection coefficient can be used to estimate the economic loss of the hospital,timely adjust infection control measures,and reduce the incidence of HAI.

AIM To study the neoflavonoids from Dalbergia cochinchinensis Pierre ex Laness and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells.METHODS The 70%ethanol extract from D.cochinchinensis was isolated and purified by silica gel,Sephadex LH-20 and reverse-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The CCK-8 method was used to detect their activities on H9c2 cells and protective effects on hypoxia-reoxygenation injury of H9c2 cells,and their structure-activity relationship was analyzed.RESULTS Twelve compounds were isolated and identified as latifolin(1),5-O-methyllatifolin(2),mimosifoliol(3),5-O-methydalbergiphenol(4),dalbergiphenol(5),cearoin(6),2,4-dihydroxy-5-methoxy-benzophenone(7),2-hydroxy-4,5-dimethoxybenzophenone(8),melannoin(9),2,2′,5-trihydroxy-4-methoxybenzophenone(10),dalbergin(11),4-methoxydalbergione(12).The dalbergiphenols and dalbergins had little toxicity to H9c2 cells,and dalbergiphenols had strong activity against hypoxia-reoxygenation injury of H9c2 cells.CONCLUSION Compound 8 is a new natural product.Compounds 4,9 are isolated from this plant for the first time.Dalbergiphenols may be the main neoflavonoids against hypoxia-reoxygenation injury of H9c2 cells.

AIM: To detect the expression of P53 and mTOR in pterygium tissues and healthy conjunctival tissues, and to explore the relationship between the expression of P53 and mTOR, and the relationship between the expression of P53 and mTOR and the important clinical features of pterygium.METHODS: The surgical specimens of 43 patients(43 eyes)who underwent pterygium excision and autologous conjunctival transplantation in the First Affiliated Hospital of Shihezi University from November 2022 to May 2023 were collected. Healthy conjunctiva group was selected from the healthy conjunctival tissue that originated from the temporal conjunctiva of 13 patients. Totally 10 pterygium specimens and 6 normal conjunctival specimens were selected and the qPCR was used to detect the mRNA expression levels of P53 and mTOR in pterygium and normal conjunctival tissues. Another 33 cases of pterygium and 7 cases of normal conjunctival tissues were collected and the expression of P53 and mTOR in pterygium and normal conjunctival tissues were detected by immunohistochemistry. IPP6.0 software was used to calculate the average optical density, the correlation between the expression levels of P53 and mTOR, and the correlation between the expression levels of P53 and mTOR and the important clinical features of pterygium were analyzed.RESULTS: According to qPCR results, the mRNA expression levels of TP53 and mTOR in the pterygium group were significantly higher than those in the healthy conjunctiva group(all P<0.05). According to the immunohistochemical staining results, the expression levels of P53 and mTOR proteins in the pterygium group were significantly higher than those in the healthy conjunctiva group(P<0.05). The expression of P53 was positively correlated with the expression of mTOR(r=0.417, P<0.05). The expression of P53 in the group of outdoor activity time > 3 h was higher than that in the group of outdoor activity time ≤3 h(P<0.05). The expression of P53 in the group of pterygium head invasive limbal distance > 2 mm was higher than that in the group of pterygium head invasive limbal distance ≤2 mm(P<0.05). There was no difference in the expression of pterygium between the two groups of patients aged > 40 years and ≤40 years(P>0.05). There was no significant difference in the expression of mTOR between the groups of outdoor activity time > 3 h and ≤3 h, the group of pterygium head invasion distance > 2 mm and ≤2 mm, and the group of > 40 years old and ≤40 years old(all P>0.05). The expression of P53 was positively correlated with the duration of outdoor activities(r=0.484, P<0.01)and the distance of limbal invasion(r=0.479, P<0.01). The expression of mTOR was not correlated with age, duration of outdoor activities, and distance of limbus invasion(all P>0.05).CONCLUSION: The overexpression of P53 and mTOR in pterygium showed a positive correlation, suggesting that the abnormal expression of P53 and mTOR may play a role in the pathogenesis of pterygium, which provides an experimental basis for further exploring the pathogenesis of pterygium; the expression of P53 is positively correlated with the time of outdoor activities and the distance of pterygium invasion. The P53 plays a role in evaluating the severity of pterygium, and provides new ideas for the clinical diagnosis and treatment of pterygium.

Objective To evaluate the effect of sodium hyaluronate combined with recombinant human epidermal growth factor(rhEGF)in the treatment of dry eye after cataract surgery.Methods Patients with dry eye after cataract surgery were divided into treatment group and control group.The control group was treated with sodium hyaluronate eye drops via dropping into the conjunctival sac,a drop per dose,tid,for 4 weeks.On this basis,the treatment group was treated with rhEGF eye drops via dropping into the conjunctival sac,1-2 drops per dose,tid,for 4 weeks.The two groups were compared on overall clinical efficacy,dry eye symptoms before treatment and after 4 weeks of treatment.Tear-film breakup time(BUT),basic tear secretion test(schirmer Ⅰ test,SⅠT),corneal fluorescein staining(CFS)score,meibomian gland yield secretion score(MGYSS),and the levels of tear inflammatory factors were compared between two groups before treatment and after 4 weeks of treatment.The safety was evaluated.Results Finally,41 cases and 39 cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates in the treatment group and the control group were 95.12％and 79.49％,with statistically significant difference(P＜0.05).After 4 weeks of treatment,dry eye symptom scores of the treatment group and control group were 1.42±0.18 and 2.31±0.26;BUT were(11.89±1.26)and(10.46±1.27)s;SⅠT were(10.12±1.35)and(8.45±0.87)mm;CFS scores were 0.83±0.11 and 1.94±0.25;MGYSS scores were 10.85±1.17 and 12.43±1.56;interleukin-1β levels in tears were(35.26±3.53)and(74.12±7.55)ng·L-1;interleukin-6 levels were(8.35±0.86)and(12.41±12.56)pg·mL-1.Compared with the control group,the above indexes in the treatment group were statistically significant(all P＜0.05).The incidence rates of adverse drug reactions in the treatment group and the control group were 12.20％and 10.26％,without statistically significant difference between the groups(P＞0.05).Conclusion Sodium hyaluronate combined with rhEGF can significantly improve dry eye symptoms after cataract surgery,enhance the stability of tear film,reduce tear inflammatory factors,and protect the integrity of meibomian gland.