BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

This article discussed the evolution of the traditional preparation process of Pinelliae Rhizoma Fermentata.The production methods for Pinelliae Rhizoma Fermentata in Song Dynasty include cake-making of Pinelliae Rhizoma together with ginger juice and fermentation after cake-making,and the former method of cake-making was the mainstream.The process technology in Jin and Yuan Dynasties inherited from that in Song Dynasty,and the application of Pinelliae Rhizoma Fermentata had certain limitations.The medical practitioners of Ming Dynasty elucidated the mechanism of processing of Pinelliae Rhizoma Fermentata,and proposed the view of"sliced Pinelliae Rhizoma being potent while fermented Pinelliae Rhizoma being mild".In the Ming Dynasty,LI Shi-Zhen defined the cake-making process and fermentation process for Pinelliae Rhizoma,and HAN Mao's Han Shi Yi Tong(Han's Clear View of Medicine)contained five prescriptions for the processing of Pinelliae Rhizoma Fermentata,which had the epoch-making signficance in the expansion of prescriptions for the processing of Pinelliae Rhizoma Fermentata.In the Qing Dynasty,HAN Fei-Xia's ten methods for making Pinelliae Rhizoma Fermentata were summarized on the basis of the methods recorded in Han Shi Yi Tong,and at that time,the processing of Pinelliae Rhizoma Fermentata and the preparation of Massa Medicata Fermentata interacted with each other.After the founding of the People's Republic of China,the local experience in the preparation of Pinelliae Rhizoma Fermentata was deeply influenced by the methods in the Qing Dynasty,and the local preparation technical standards gradually became the same.Moreover,this article also explored the issues of the importance of"Pinelliae Rhizoma"and"ingredients for fermentation",the pre-treatment of Pinelliae Rhizoma,the distinction between cake-making process and fermentation process for Pinelliae Rhizoma,the amount of flour added as well as the timing of adding,the addition of Massa Medicata Fermentata powder,the role of Alum in Pinelliae Rhizoma Fermentata and so on.

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab biosimilars （Hanquyou） versus original drug （Hesaiting） in the treatment of recurrent/metastatic human epidermal growth factor receptor-2 （HER-2） positive breast cancer. METHODS A partitional survival model was constructed based on the NCT03084237 trial data. The simulation period was 3 weeks， and the simulation time was 10 years. Using costs and quality-adjusted life year （QALY） as the output indicator， the cost- utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the robustness of the basic analysis. RESULTS The costs of the trastuzumab biosimilars group and original drug group were 111 516.72 yuan and 111 122.30 yuan respectively， with health utility values of 1.52 QALYs and 1.36 QALYs， and ICER of 2 465.12 yuan/QALY， which were less than 3 times China’s per capita gross domestic product （GDP） in 2023 as the threshold for willingness-to-pay （WTP） （268 200 yuan/QALY）. Univariate sensitivity analysis showed that the cost of the trastuzumab biosimilars and original drug had a great impact on the ICER. The probabilistic sensitivity analysis showed that the probability of trastuzumab biosimilars being cost-effective was 100% at WTP threshold of 14 902 yuan/QALY. CONCLUSIONS When WTP threshold is 3 times China’s GDP in 2023 （268 200 yuan/QALY）， compared with original drug， trastuzumab biosimilars have good cost-effectiveness in the treatment of recurrent/metastatic HER-2 positive breast cancer.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg^-1）， a HYT group （12.06 g·kg^-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg^-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg^-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg^-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg^-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.

Pancreatic cancer (PC) is a highly fatal disease which originated from pancreatic epithelial and acinar cells, and the survival rate of pancreatic cancer patients is only about 12%. Approximately 95% of pancreatic cancer presents as ductal adenocarcinoma (PDAC). Pancreatic cancer is characterized by high aggressiveness, rapid progression and progression, and high resistance to treatment. Common somatic mutated genes in the early stage of pancreatic cancer include KRAS, CDKN2A, TP53, and SMAD4. Most pancreatic cancer patients are affected by environmental risk factors such as age, sex and diet. Malignant pancreatic cancer is associated with non-invasive, preneoplastic lesions that are thoughted to be precursors, such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN) and mucinous cystadenoma (MCN). In recent years, people have gradually improved the therapy and diagnosis of pancreatic cancer, and the contribution of imaging technology, which enhancing the usage of minimally invasive pancreatectomy that typically includes pancreaticoduodenectomy and distal pancreatectomy. However, combined administration of the chemotherapeutic gemcitabine and erlotinib is still considered a potential first-line treatment for advanced pancreatic cancer, but the development of chemoresistance often leads to poor therapeutic outcomes. Based on the current research progress for pancreatic cancer, its treatment currently remains one of the most important challenges in the medical field. Although some new treatment options have been provided, there were minor clinical success achieved and therefore new safe and effective therapies of pancreatic cancer are still an urgent need for patients. Among these new therapies for pancreatic cancer, short peptide-based treatment protocols have attracted great attention. Peptide is a compound formed by linking α-amino acids together in peptide chains. It is also an intermediate product of proteolysis. The short peptide-based therapy has many advantages such as precise targeting, easy preparation and low toxicity. Short peptides usually act as tumor suppressors by targeting and recognizing tumor-specific expressed proteins. Currently, there is an increased interest in peptides in pharmaceutical and development research, and approximate 140 peptide therapeutics are currently being evaluated in clinical trials. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity and simplicity of modification. Peptides have high bioactivity and excellent biodegradability. Clinically, short peptides are increasingly used as combination drugs with chemotherapy for tumor treatment. Peptides can induce cancer cell death by numerous mechanisms and peptides have emerged as a promising drug for the treatment of pancreatic cancer. Here we mainly review the roles of peptides on Wnt/β-catenin, NF-κB, autophagy, and the use of peptides as tracer in pancreatic cancer. We also analyzed the benefits and disadvantages existing in the development process of short peptides, which provide the feasibility of targeted short peptides to become new therapeutic approaches for cancer therapy.

Objective To analyze the rules and characteristics of cross-allergy cases related to drug-related medical disputes,and to provide reference for the formulation of cross-allergy prescription review strategy.Methods The judgments of cross-allergy related medical damage liability disputes recorded in the legal document database of Beijing Yingke Law Firm and the Chinese Judgment Document Network database from August 2010 to June 2023 were analyzed,the causes of relevant disputes were summarized and analyzed,and more comprehensive response measures were formulated.Results A total of 65 judgments were retrieved,and seven judgments were included.The main drugs causing cross allergy were antibiotics(penicillins,cephalosporins and sulfonamides).Seven cases of medical disputes,all of which were ruled by the court that the medical party had medical errors due to cross-allergies,and had to bear 30％to 80％of the compensation liability.The main reasons for the punishment were that the doctor did not pay enough attention to the patient's past history of allergy and chose unreasonable drugs.Conclusion Medical institutions can reduce the risk of cross-allergy by means of information technology,and play the role of pharmacists in prescription review and pharmaceutical care.Physicians should pay attention to the patient's past history,earnly inquire,strengthen medication education and monitoring,reduce the threat of adverse reactions to the patient's life safety and related drug disputes,and protect the legitimate rights and interests of both doctors and patients.

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Objective:To investigate the clinicopathological features, classification, and genetic characteristics of common lymphatic malformation (CLM) in superficial soft tissue.Methods:A retrospective study of 110 patients with the diagnosis of CLM at the Henan Province People′s Hospital, China from August 2019 to August 2022 was performed. The clinicopathological features, relevant immunohistochemical (IHC) staining results, and fluorescence quantitative PCR of PIK3CA mutation were analyzed, and patients were followed up.Results:Among the 110 CLM patients, there were 53 males and 57 females; 65 cases (65/110, 59.1%) were first detected when the patients were≤2 years old. The most common location was the head and neck in 41 cases (41/110, 37.3%). Clinically, 102 cases (102/110, 92.7%) were solitary, 83 cases (83/110, 75.5%) were skin-colored, 69 cases (69/110, 62.7%) had indistinct borders, and 10 cases (10/110, 9.1%) had diffuse and severe macroscopic manifestations. There were 52 macrocystic type (52/110, 47.3%), 23 microcystic type (23/110, 20.9%), and 35 combined type (35/110, 31.8%). The macrocystic CLM presented as soft, translucent masses with large cystic cavities on the cut surface, and histologically they were composed of large, irregularly dilated channels that were thicker with irregular smooth muscle and lymphocytic infiltration. Microcystic CLM showed wartlike projections or translucent blisters on the skin, with small honeycomb structures on the cut surface, and histologically consisted of round or angular dilated small lymphatic vessels with little or no smooth muscle. The combined CLM had both macrocystic and microcystic morphologies. IHC staining showed that the lymphatic endothelial cells were positive for LYVE-1, D2-40, PROX1, CD31, and VEGFR3 but negative for CD34; in the macrocystic and combined CLM vessel walls were positive for SMA. Eight of 13 CLM had PIK3CA mutation. All patients were followed up, and 24 (24/110, 21.8%) had relapses, which more frequently occurred in combined type, followed by microcystic type.Conclusions:CLM is a congenital vascular malformation composed of dilated, abnormal lymphatic channels, with PIK3CA mutation. There are significant differences in clinicopathological characteristics among the different types. Since microcystic and combined CLM are prone to recurrence, accurate pathological subtyping is necessary to guide treatment and to predict prognosis.