Atherosclerosis is a complex pathological condition resulting from lipid deposition， chronic inflammatory responses， and fibrosis， with a prolonged disease course and multifactorial etiology. Based on the traditional Chinese medicine （TCM） theory of accumulation syndrome， atherosclerosis can be classified under this category， with its pathogenesis involving phlegm， blood stasis， deficiency， and accumulation. This paper proposed a stage-based intervention strategy using the four therapeutic principles of "attacking， supplementing， dispersing， dissipating"， and divided into six stages based on the pathological progression， including the stage of accumulation before formation， the stage of accumulation already formed， the stage of nucleus accumulation， the stage of nucleus accumulation decay， the stage of nucleus accumulation consolidation， and the stage of severe stenosis of nucleus. At different stages， the intervention focuses on reinforcing healthy qi and consolidating the root， tonifying the kidneys and spleen， dispersing and removing turbidity， removing phlegm stagnation， promoting qi circulation， dispersing accumulations and removing stasis， attacking accumulation and expelling stasis， directing the turbid downward and dispersing accumulation， and treatment would be adjusted based on specific symptoms， which provides a theoretical framework for the prevention and treatment of atherosclerosis with TCM.

[摘 要] 目的：探讨溶酶体相关膜蛋白3（LAMP3）与转录激活因子4（ATF4）在宫颈癌中的表达及其与临床病理参数的相关性。方法：采用免疫组化SP法检测正常宫颈组织、宫颈上皮内病变组织及宫颈癌组织中LAMP3与ATF4的表达情况，分析两种蛋白与宫颈癌患者临床病理参数之间的关系，并且分析两种蛋白的相关性。结果：LAMP3在正常宫颈组及高级别鳞状上皮内病变组中均为阴性或低表达，在宫颈癌中高表达率为38.3%，差异有统计学意义（χ2 = 14.113，P = 0.001）。ATF4在正常宫颈组中高表达率为26.7%，在高级别鳞状上皮内病变组中高表达率为10.0%，在宫颈癌组中高表达率为58.3%，差异有统计学意义（χ2 = 11.078，P = 0.004）。LAMP3的表达与宫颈癌FIGO分期（χ2 = 10.139，P = 0.006）、淋巴结转移（χ2 = 8.475，P = 0.004）有关，差异均有统计学意义。ATF4的表达在宫颈癌病灶大小（χ2 = 4.578，P = 0.032）、FIGO分期（χ2 = 8.971，P = 0.009）、淋巴结转移（χ2 = 7.881，P = 0.005）等方面的差异均有统计学意义。LAMP3与ATF4在宫颈癌中的表达呈正相关（r = 0.388，P = 0.002）。结论：LAMP3与ATF4在宫颈癌组织中表达升高，两者的表达程度具有相关性，且在宫颈癌的发生发展中发挥重要的促进作用，有望成为宫颈癌治疗的潜在靶点。

TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Objective To investigate the characteristics of human papillomavirus (HPV) prevalence and genotype distribution of 18 535 cases in Yuncheng . Methods A sample of 18535 residents who underwent HPV testing in our hospital from August 2020 to September 2023 were enrolled, and HPV genotyping was done to all samples. Then the rate of HPV infection, age distribution, genotype distribution, and multiple infections were statistically analyzed. Results Of the 18,535 subjects included, a total of 4,639 tested positive for HPV, demonstrating a positive rate of 25.03%. The positive rate of HPV infection varied among different age groups (χ²=29.587, P<0.05), with higher rates found in <25 years old group (29.61%) and >60 years old group (25.89%). Overall, 23 genotypes, covering 5315 viruses, were detected. There were 5 low-risk genotypes with the highest percentage of HPV42 (9.29%), and there were 18 high-risk genotypes with HPV52, HPV58, HPV66 and HPV53, subtypes as the most frequent subtypes, accounting for 13.64%, 8.97%, 7.41% and 7.04%, respectively. The type of HPV infection was predominantly single infections, with an overall single infection rate of 21.62% (4008/18535), which accounted for 86.40% (4 008/4 639) of all positive cases, and a multiple genotype infections rate of 3.40% (631/18535). The 25-34 year old group accounted for the largest proportion of single infections (25.12%), while the <25 year old group accounted for the largest proportion of multiple genotype infections (30.74%). Conclusion The prevalence rate of HPV infection in Yuncheng is 25.03%, with a higher positive rate in the <25 years age group and the >60 years age group. A total of 23 HPV genotypes are detected, of which the main genotypes are HPV42, HPV58, HPV66 and HPV53, and the type of infection is dominated by single infections.

Objective To observe the effect of Shenqi Chongcao (SQCC) Formula on the ASS1/src/STAT3 signaling pathway in a rat model of lung fibrosis and explore its therapeutic mechanism. Methods A total of 120 male SD rats were divided equally into 5 groups, including a blank control group with saline treatment and 4 groups of rat models of idiopathic pulmonary fibrosis induced by intratracheal instillation of bleomycin. One day after modeling, the rat models were treated with daily gavage of 10 mL/kg saline, SQCC decoction (0.423 g/kg), pirfenidone (10 mL/kg), or intraperitoneal injection of arginine deiminase (ADI; 2.25 mg/kg, every 3 days) for 28 days. After the treatments, the lung tissues of the rats were collected for calculating the lung/body weight ratio, observing histopathology using HE and Masson staining, and analyzing the inflammatory cells in BALF using Giemsa staining. Serum chemokine ligand 2 (CCL2) and transforming growth factor-β1 (TGF-β1) levels were measured with ELISA. The protein expressions of src, p-srcTry529, STAT3, and p-STAT3Try705 and the mRNA expressions of ASS1, src and STAT3 in the lung tissues were detected using Western blotting and RT-qPCR. Results The neutrophil, macrophage and lymphocyte counts and serum levels of CCL2 and TGF-β1 were significantly lower in SQCC, pirfenidone and ADI treatment groups than in the model group at each time point of measurement (P<0.05). P-srcTry529 and p-STAT3Try705 protein expression levels and ASS1, src, and STAT3 mRNA in the lung tissues were also significantly lower in the 3 treatment groups than in the model group (P<0.05). Conclusion SQCC Formula can alleviate lung fibrosis in rats possibly by activating the ASS1/src/STAT3 signaling pathway in the lung tissues.

Objective:To investigate the relationship between the expression levels of serum glycogen synthase kinase-3β (GSK-3β) and mothers against decapentaplegic homolog 4 (SMAD4) in patients with acute coronary syndrome (ACS) and the severity and prognosis of coronary artery disease.Methods:A total of 192 ACS patients admitted to Shandong First Medical University Affiliated Qingdao Hospital from June 2020 to May 2022 were selected as the ACS group, while 192 non ACS patients admitted to the same hospital were selected as the non ACS group. Enzyme-linked immunosorbent assay method was applied to determine the expression levels of serum GSK-3β and SMAD4 in two groups. The Gensini score was applied to evaluate the degree of coronary artery disease in patients, Spearman method was applied to analyze the correlation between serum GSK-3β, SMAD4 expression levels and Gensini score in ACS patients. Receiver operating characteristic (ROC) curve was applied to analyze the predictive efficacy of serum GSK-3β and SMAD4 levels on the prognosis of ACS patients.Results:The serum levels of GSK-3β and SMAD4 in the ACS group were significantly higher than those in the non ACS group: (2.70 ± 0.40) μg/L vs. (2.24 ± 0.41) μg/L, (12.19 ± 2.10) μg/L vs. (9.79 ± 2.82) μg/L, and there were statistical differences ( P<0.05). The serum levels of GSK-3β and SMAD4 in ACS patients with mild, moderate and severe coronary artery disease increased sequentially ( P<0.05). Spearman analysis showed that serum GSK-3β and SMAD4 levels in ACS patients were positively correlated with Gensini total score ( r = 0.569 and 0.587, P<0.01). In ACS patients, 48 cases had poor prognosis, and the incidence of poor prognosis was 25.00% (48/192); 144 cases had a good prognosis. The serum levels of GSK-3β and SMAD4 in ACS patients with poor prognosis were significantly higher than those in ACS patients with good prognosis: (3.15 ± 0.53) μg/L vs. (2.55 ± 0.36) μg/L, (14.03 ± 2.08) μg/L vs. (11.58 ± 2.11) μg/L, and there were statistical differences ( P<0.05). The ROC curve result indicated that the area under the curve (AUC) for predicting poor prognosis in ACS patients with serum GSK-3β and SMAD4 levels alone and in combination was 0.799, 0.784 and 0.858, respectively, the AUC predicted by the combination of the two was obviously higher than the AUC predicted separately ( Z = 2.04 and 2.75, P = 0.041 and 0.006). Conclusions:The expression levels of GSK-3β and SMAD4 in the serum of ACS patients are abnormally elevated. They are positively correlated with the degree of coronary artery disease in ACS patients, and both have good predictive power for adverse prognosis in ACS patients, while the combined use of the two has better predictive performance.