Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

In this paper， by referring to ancient and modern literature， the textual research of Kochiae Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， taste and efficacy， harvesting time， processing and compatibility taboo， so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation， it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic， and has been used as the official name throughout history. It is also known by other names such as Dimai， Dikui， and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia， which is consistent throughout history. In the Han dynasty， it was recorded that Kochiae Fructus was produced in Jingzhou（Hubei province）， while modern literature records its distribution throughout the country， so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn， and the quality is best when it is full， gray green in color， and no impurities. There are two processing methods for its origin：from the Southern and Northern dynasties to the Ming dynasty， it was dried in the shade， and after the founding of the People's Republic of China， it was dried in the sun. There are few records about the processing of Kochiae Fructus， and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar， and the leaves are taken in April and May， processing in the place of origin is shade drying， the processing methods include burning ash and frying frost， pounding juice and wine soaking. For internal use， it is mostly decocted or mashed， while for external use， it is mostly washed with decoction or taken in a soup bath. Throughout history， it has been recorded that Kochiae Fructus is bitter and cold， and is mainly used for treating bladder fever. After the founding of the People's Republic of China， most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia， it has been recorded that Kochiae Fructus has a pungent and bitter taste， and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness， dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history， it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times， it has been used to regulate the liver， spleen and large intestine meridians， with functions such as clearing heat and detoxifying， and diuresis. Based on the textual research， it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus， and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements， the raw products is taken into medicine.

In this paper， by referring to ancient and modern literature， the textual research of Cnidii Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， nature and flavour， efficacy， harvesting and processing， compatibility taboo and others， so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research， it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic， the materia medica of all dynasties was named Shechuangzi， and there are also aliases such as Shesu， Shemi， and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri， and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty， the origin of Cnidii Fructus was Zibo， Shandong province. During the Five dynasties， it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province， the Song dynasty added Shangqiu in Henan province， and it was considered that Yangzhou， Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China， the origin is clearly distributed throughout the country. For its quality evaluation， generally full grain， gray yellow color， strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month， and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products， mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past， there were also stir-frying with honey， stir-frying with salt and rice wine， immersing and steaming with rice wine and other methods. In recent times， it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter， Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm， acted on the kidney meridian， and had small toxicity. After the founding of the People's Republic of China， most of the literature classified it as a medicine to attack poison， kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness， destroying parasites and elieving itching， warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research， it is suggested that when developing the famous classical formulas containing Cnidii Fructus， the source shall be the dried ripe fruit of C. monnieri， and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas， the raw products can be taken into medicine.

Germplasm degeneration occurs during the long-term cultivation of root-and rhizome-derived traditional Chinese medicine(RR-TCM), which seriously restricts the high-quality development of their industry. Therefore, it is urgent to solve the problem of germplasm degeneration through variety breeding. In this paper, based on previously published research articles, monographs, and news reports, the research progresses on the number and origins, breeding methods, and selection of new varieties of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020) were summarized and analyzed. The results show that there are 169 kinds of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020), originated from 223 origins with three breeding methods(i.e., seed propagation, vegetative reproduction, and tissue culture), and there are 215 species derived from seed propagation, 177 species derived from vegetative reproduction, and 164 species derived from tissue culture. To date, there are 62 origins breeding new varieties through conventional breeding, cross breeding, mutation breeding, ploidy breeding, or modern biotechnology breeding methods, including 57 origins breeding 145 new varieties through conventional breeding, 10 origins breeding 43 new varieties through mutation breeding, and seven origins breeding 12 new varieties through cross breeding method. They are used mainly to improve yield, disease resistance, and active ingredient content, but only a few new varieties have been widely used. This review will provide useful references in variety breeding, quality breeding, and standardized planting of RR-TCM.
Plant Breeding/methods* ; Plant Roots/growth & development* ; Rhizome/growth & development* ; Drugs, Chinese Herbal ; Plants, Medicinal/classification* ; Medicine, Chinese Traditional

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.