The p53 protein is an essential tumor suppressor in the human body that plays a critical role in preventing tumor formation by controlling cell cycle arrest and promoting apoptosis. Mutations in the p53 gene are frequently observed in more than 50% of tumor tissues and lead to the generation of mutant p53 proteins, which not only have a dominant-negative effect (DN) that hinders the function of wild-type p53 protein but also have gain-of-function (GOF) effects that stimulate tumor development by regulating cell metabolism, invasion, migration, and other processes. Therefore, mutant p53 protein has become a specific drug target for cancer therapy. However, the lack of a drug-binding pocket and smooth surface of mutant p53 proteins have made them undruggable targets for a long time. In recent years, with the development of high-throughput screening technology and an enhanced understanding of the structure and conformational changes exhibited by mutant p53 proteins, a multitude of small molecule compounds directed against mutant p53 protein have been identified, exhibiting substantial in vitro anti-tumor efficacy. Moreover, some of these compounds have entered clinical trials. This review summarized the direct and indirect strategies for the treatment of cancers targeting mutant p53, with a primary focus on the mechanisms of action of small molecule compounds that reactivate mutant p53 protein or degrade mutant p53 protein. The aim is to provide assistance for the development of innovative drugs targeting mutant p53 protein in the future.

Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.

Aim To explore the effect of serum contai-ning Duhuo Jisheng Decoction on the proliferation,ap-optosis and inflammation of fibroblast-like synoviocytes(FLS)induced by tumor necrosis factor-α(TNF-α)in rheumatoid arthritis(RA)and to reveal the under-lying mechanism.Methods The MH7A cells were divided into five groups:normal group(10％blank se-rum),model group(10 μg·L-1 TNF-α+10％blank serum),Duhuo Jisheng Decoction low(10 μg·L-1 TNF-α+2.5％drug-containing serum+7.5％blank serum),medium(10 pg·L-1 TNF-α+5％drug-con-taining serum+5％blank serum),high(10 μg·L-1 TNF-α+10％drug-containing serum)dose group.The concentration of serum containing Duhuo Jisheng Decoction was screened by MTT method.Cell prolifer-ation was detected using EdU staining.The expression of proliferation marker Ki67 was detected using immu-nofluorescence staining.The apoptosis rate was meas-ured by flow cytometry.The contents of IFN-γ,IL-4,IL-6 and IL-10 in each group were detected by ELISA.The mRNA and protein expression of Bax,Bcl-2,caspase-3 and TLR4/MyD88/NF-κB signaling pathway were detected by RT-qPCR and Western blot.Results Compared with the normal group,the cell prolifera-tion activity of the model group significantly increased,and the level of apoptosis decreased.The content of IFN-γ and IL-6 increased,and the content of IL-4 and IL-10 decreased.The TLR4/MyD88/NF-κB signaling pathway was activated.After the intervention of low,medium and high dose groups of serum containing Du-huo Jisheng Decoction,it could effectively improve the abnormal proliferation of cells and enhance apoptosis.At the same time,it inhibited the inflammatory re-sponse and the activation of TLR4/MyD88/NF-κB sig-naling pathway.Conclusions The serum containing Duhuo Jisheng Decoction can inhibit the abnormal pro-liferation of RA-FLS induced by TNF-α and the secre-tion of pro-inflammatory factors,and enhance apoptosis and anti-inflammatory levels.The mechanism may be related to the regulation of TLR4/MyD88/NF-κB sig-naling pathway.

OBJECTIVES: To study the genetic polymorphism and population genetic parameters of 16 X-STR loci in Xinjiang Uygur population. METHODS: The Goldeneye^® DNA identification system 17X was used to amplify 16 X-STR loci in 502 unrelated individuals (251 females and 251 males). The amplified products were detected by 3130xl genetic analyzer. Allele frequencies and population genetic parameters were analyzed statistically. The genetic distances between Uygur and other 8 populations were calculated. Multidimensional scaling and phylogenetic tree were constructed based on genetic distance. RESULTS: In the 16 X-STR loci, a total of 67 alleles were detected in 502 Xinjiang Uygur unrelated individuals. The allele frequencies ranged from 0.001 3 to 0.572 4. PIC ranged from 0.568 8 to 0.855 3. The cumulative discrimination power in females and males were 0.999 999 999 999 999 and 0.999 999 999 743 071, respectively. The cumulative mean paternity exclusion chance in trios and in duos were 0.999 999 997 791 859 and 0.999 998 989 000 730, respectively. The genetic distance between Uygur population and Kazakh population was closer, and the genetic distance between Uygur and Han population was farther. CONCLUSIONS The 16 X-STR loci are highly polymorphic and suitable for identification in Uygur population, which can provide a powerful supplement for the study of individual identification, paternity identification and population genetics.
Female ; Humans ; Male ; DNA, Ribosomal ; Ethnicity/genetics* ; Gene Frequency ; Paternity ; Phylogeny ; Polymorphism, Genetic ; Microsatellite Repeats ; Chromosomes, Human, X/genetics*

OBJECTIVES: To investigate the genetic polymorphism of InDel loci in SifalnDel 45plex system in the Han population in Jiangsu Province and the Mongolian population in Inner Mongolia, and to evaluate the effectiveness of the system in forensic medicine. METHODS: SifaInDel 45plex system was used for genotyping in blood samples of 398 unrelated individuals from the above two populations, and allele frequencies and population genetic parameters of the two populations were calculated respectively. Eight intercontinental populations in the gnomAD database were used as reference populations. The genetic distances between the two studied populations and eight reference populations were calculated based on the allele frequencies of 27 autosomal-InDels (A-InDels). The phylogenetic trees and multidimensional scaling (MDS) analysis diagrams were constructed accordingly. RESULTS: Among two studied populations, the 27 A-InDels and 16 X-InDels showed no linkage disequilibrium between each other and the allele frequency distributions were in Hardy-Weinberg equilibrium. The CDP of the 27 A-InDels in two studied populations were all higher than 0.999 999 999 9, and the CPE_trio were all less than 0.999 9. The CDP of the 16 X-InDels in Han in Jiangsu and Mongolian in Inner Mongolia female and male samples were 0.999 997 962, 0.999 998 389, and 0.999 818 940, 0.999 856 063, respectively. The CMEC_trio were all less than 0.999 9. The results of population genetics showed that the Jiangsu Han nationality, Inner Mongolia Mongolian nationality and East Asian population clustered into one branch, showing closer genetic relationship. The other 7 intercontinental populations clustered into another group. And the above 3 populations displayed distant genetic relationships with the other 7 intercontinental populations. CONCLUSIONS The InDels in the SifaInDel 45plex system have good genetic polymorphism in the two studied populations, which can be used for forensic individual identification or as an effective complement for paternity identification, and to distinguish different intercontinental populations.
Humans ; Phylogeny ; Gene Frequency ; Polymorphism, Genetic ; Genetics, Population ; Asian People/genetics* ; China ; INDEL Mutation

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
Humans ; Practice Guidelines as Topic

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca²⁺ current. Using noise analysis of Ca²⁺ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca²⁺ channels along with Ca_V1.3 expression. All these changes could act synergistically to enhance the Ca²⁺ influx into IHCs. Inhibition of intracellular Ca²⁺ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
Animals ; Calcium ; Exocytosis ; Hair Cells, Auditory, Inner ; Mice ; Sodium Salicylate/pharmacology* ; Tinnitus/chemically induced*

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.
Biomarkers ; Capsules ; Drugs, Chinese Herbal/pharmacology*

Asians ; China ; Humans ; Hypertension/drug therapy* ; Practice Guidelines as Topic ; Writing

OBJECTIVE: To investigate the expression and clinical significance of soluble interleukin-2 receptor(sIL-2R) in patients with multiple myeloma(MM). METHODS: 54 newly diagnosed MM patients in the Second Affiliated Hospital of Fujian Medical University from February 2020 to December 2021 were selected as the observation group, and 60 healthy people in our hospital in the same period were selected as the control group. The expression levels of sIL-2R in the serum of the two groups were detected by enzyme-linked immunosorbent assay. The differences of sIL-2R expression level among different clinical parameter groups in MM patients were compared. The clinical parameters include:gender, age, ISS stage, hemoglobin, albumin, serum creatinine, lactate dehydrogenase and β₂-microglobulin, blood calcium, bone marrow plasma cell ratio and treatment response. The relationship between sIL-2R expression level and progression-free survival(PFS) and overall survival(OS) in MM patients were analyzed. RESULTS: The expression of serum SIL-2R in MM patients was significantly higher than that in healthy control group (P<0.05). The expression of sIL-2R in MM patients who did not achieve complete remission(CR) was significantly higher than those of CR patients (P=0.037). There was no significant difference in the expression of serum sIL-2R between the groups of different sex, age, ISS stage, hemoglobin concentration, albumin content, serum creatinine level, lactate dehydrogenase level, the content of β₂-microglobulin, the concentration of blood calcium, and the proportion of bone marrow plasma cells(P>0.05). The PFS of sIL-2R high expression group(15 months) was shorter than that of sIL-2R low expression group (22 months), which was significant difference (P=0.041). But there was no significant difference in OS between sIL-2R high expression group and sIL-2R low expression group (P=0.124). Univariate analysis results showed that the high expression of serum sIL-2R was associated with poor PFS in MM patients. Multivariate analysis results showed that the high expression of serum sIL-2R was still an independent adverse prognostic factor for PFS in MM patients, However, the expression of serum sIL-2R was not statistically significant in evaluating OS in MM patients by univariate and multivariate analysis. CONCLUSION The expression of serum sIL-2R in MM patients was significantly higher than that in healthy people. Serum sIL-2R is an independent prognostic factor of PFS in MM patients.
Humans ; Calcium ; Clinical Relevance ; Creatinine ; Lactate Dehydrogenases ; Multiple Myeloma ; Receptors, Interleukin-2