Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Objective To observe the effect of parecoxib sodium combined with dexmedetomidine preemptive analgesia on postoperative analgesia in patients with modified radical mastectomy for breast cancer.Methods Patients who underwent modified radical mastectomy for breast cancer were randomly divided into control group and treatment group based on simple binary randomization by random number table method.In the control group,"0.05 mg·kg-1 midazolam+1.0-1.5 mg·kg-1 propofol+0.4 μg·kg-1sufentanil citrate+0.15 mg·kg-1 phenylsulfonyl cisatracurium"was used for induction and maintenance of anesthesia.In the treatment group,the induction and maintenance of anesthesia was performed with the protocol of"parecoxib sodium 40 mg+dexmedetomidine 0.5 μg·kg-1·h-1)continuous pumping"on the basis of control group,and mechanical ventilation was performed by tracheal intubation 5 min after induction.The effect of pre-analgesia,postoperative sedation,hemodynamic indexes,surgical improvement indexes and application safety were observed by groups.Results There were 46 patients in each group.Pain visual analogue scores at 6,12 and 24 h in treatment group were 2.09±0.72,4.17±1.07 and 4.07±1.05,lower than those in control group,which were 2.61±1.03,4.76±1.27 and 4.65±1.11,the differences were statistically significant(all P＜0.05).The Ramsay sedation scores of the treatment group and the control group at 6 h after surgery were(2.85±0.62)and(2.11±0.73)points,respectively;the sedation scores of Ramsay at 12 h were 1.41±0.28 and 1.06±0.15,respectively.At 24 h,the sedation scores of Ramsay were 1.15±0.18 and 0.64±0.13,respectively,and the difference was statistically significant(P＜0.05).HR and MAP of treatment group and control group at T2 and T3 were significantly lower than those at T1 and T0(P＜0.05),there were no difference in HR and MAP between treatment group and control group at T2 and T3(P＜0.05).Operation time,recovery time after operation and intraoperative blood loss in treatment group were significantly lower than those in control group,and the differences were statistically significant(all P＜0.05).The success rate of 12-hour postoperative analgesia in test group and control group was 82.61％(38 cases/46 cases)and 63.04％(29 cases/46 cases),respectively,and the difference was statistically significant(P＜0.05).The adverse drug reactions in treament group and control group mainly included bradycardia,headache,dizziness and nausea,and the incidence of adverse drug reactions in treatment group and control group were 13.04％(6 cases/46 cases)and 8.70％(4 cases/46 cases),respectively,the difference was no statistically significant(P＜0.05).Conclusion Parecoxib sodium combined with dexmedetomidine preemptive analgesia has significantly improved analgesia and sedative effects in modified radical mastectomy for breast cancer,can prolong sedation and analgesia time,and stably control the perioperative hemodynamics of patients.

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains unknown.We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of China. Methods In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and G5. Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to 2020.Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV.Two cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 JEV. Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.

AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P＜0.05);increased,degree of renal fibrosis,and renal fibrosis area(P＜0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and decreased expressions of IGF-1R mRNA and protein(P＜0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P＜0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P＜0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and increased expressions of IGF-1R mRNA and protein(P＜0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P＜0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.

DNA genetic markers have always played important roles in individual identification, kinship analysis, ancestry inference and phenotype characterization in the field of forensic medicine. DNA methylation has unique advantages in biological age inference, body fluid identification and prediction of phenotypes. The majority of current studies independently examine DNA and DNA methylation markers using various workflows, and they use various analytical procedures to interpret the biological information these two markers present. Integrated methods detect DNA and DNA methylation markers simultaneously through a single experimental workflow using the same preparation of sample. Therefore, they can effectively reduce consumption of time and cost, streamline experimental procedures, and preserve valuable DNA samples taken from crime scenes. In this paper, the integrated detection approaches of DNA and DNA methylation markers on different detection platforms were reviewed. In order to convert methylation modifications to detectable forms, several options were available for pretreatment of genomic DNA, including digestion with methylation-sensitive restriction enzyme, affinity enrichment of methylated fragments, conversion of methylated or unmethylated cytosine. Multiplexed primers can be designed for DNA markers and converted DNA methylation markers for co-amplification. The schemes of using capillary electrophoresis platform for integrated detection add the pretreatment of genomic DNA on the basis of detecting DNA genetic markers. DNA and DNA methylation markers are then integrated by co-amplification. But the limited number of fluorescent options available and the length of amplicons restrict the type and quantity of markers that can be integrated into a panel. Pyrophosphate sequencing also supports integrated detection of DNA and DNA methylation markers. On this platform, due to the conversion of unmethylated cytosine to thymine after treatment with bisulfite, the methylation level of CpG site can be directly calculated using the peak height ratio of cytosine bases and thymine bases. Therefore, the methylation levels and SNP typing can be simultaneously obtained. However, due to the limited read length of sequencing, the detection of markers with longer amplicons is restricted. It is not conducive to fully interpret the complete information of the target sequence. Next-generation sequencing also supports integrated detection of DNA and DNA methylation markers. A preliminary experimental process including DNA extraction, pretreatment of genomic DNA, co-preparation of DNA and DNA methylation library and co-sequencing, has been formed based on the next-generation sequencing platform. It confirmed the feasibility of next-generation sequencing technology for integrated detection of DNA and DNA methylation markers. In field of biomedicine, various integrated detection schemes and corresponding data analysis approaches of DNA and DNA genetic markers developed based on the above detection process.Co-analysis can simultaneously obtain the genomic genetic and epigenetic information through a single analytic process. These schemes suggest that next-generation sequencing may be an effective method for achieving more accurate and highly integrated detection, helping to explore the potential for application in forensic biological samples. We finally explore the impact of interactions between sites and different pretreatment methods on the integrated detection of DNA and DNA methylation markers, and also propose the challenge of applying third-generation sequencing for integrated detection in forensic samples.

Objective To compare the efficacy of blood letting under pain point touch and ultrasound-guided puncture de-compression in the treatment of acute supraspinatus muscle calcifying tendinitis.Methods From January 2020 to January 2023,45 patients with acute supraspinatus muscle calcifying tendinitis were selected and divided into treatment group and control group.In the treatment group,a total of 22 patients were treated with ultrasound-guided puncture decompression,in-cluding 16 females and 6 males,aged from 20 to 64 years old(39.31±5.80)years old,11 on the left shoulder and 11 on the right shoulder.In the control group,there were 23 cases,including 15 females and 8 males,aged from 19 to 66 years old(40.67±6.13)years old,12 on the left shoulder and 13 on the right shoulder.The treatment was treated with pain point touch bloodletting therapy.The visual analog scale(VAS)pain score,University of California,Los Angeles(UCLA)shoulder system score and shoulder Constant-Murley score were used to evaluate the therapeutic effect before treatment,1 weeks,1 month and 3 months after treatment,respectively.Results One patient in the control group gave up follow-up for personal reasons after 1 week of treatment,and the other 44 patients completed all follow-up.Six months after treatment,there were no recurrence cases in both groups.After statistical analysis,VAS pain score,UCLA score and Constant-Murley score of the treatment group and the control group were significantly different from those before treatment(P＜0.05),and the improvement was more obvious in the treatment group.There was no statistical significance between the two groups(P＞0.05).Conclusion Bloodletting under pain point touch and ultrasound-guided puncture decompression are effective in the treatment of acute calcific supraspinatus tendinitis,with simple operation and low cost,which can effectively reduce local pain and effectively improve shoulder joint function.Primary hospitals can selectively operate treatment according to their own conditions.

Objective To explore the clinical efficacies of different surgical methods for elderly patients with lumbar tuberculosis.Methods The clinical data of 289 elderly patients with lumbar tuberculosis admitted to Hebei Chest Hospital from August 2018 to August 2021 were retrospectively analyzed.According to surgical methods,the patients were divided into the posterior group(109 cases),the anterior and posterior combination group(81 cases),and the anterior group(99 cases).The time of bone graft and fusion,operation time,hospital stay,intraoperative blood loss,and complications of the three groups were collected and compared among the three groups.The spine Cobb angle was regularly determined,the correction degree was calculated;the levels of erythrocyte sedimentation rate(ESR),white blood cell count(WBC),and C-reactive protein(CRP)were collected and compared among the three groups;and the Frankel grading and visual analogue scale(VAS)scores of the three groups were compared.Results After a 2-year follow-up,there was no significant difference in the time of bone graft and fusion among the three groups(P>0.05),the anterior group had the shortest operation time,the posterior group had the shortest hospital stay,and the lowest intraoperative blood loss and incidence of complications,with statistically significant differences(P<0.05).The correction degree of the anterior and posterior combination group was better than that of the posterior group and the anterior group(P<0.05),and the Cobb angles after operation and at the last follow-up in the posterior group was better(P<0.05).The anterior and posterior combination group had better improvement effect on CRP and ESR at the last follow-up(P<0.05),the WBC level of the posterior group was lower(P<0.05).The proportions of patients in grade E of Frankel grading at the last follow-up in the three groups were higher than those after surgery(P<0.05);compared with the preoperative period,the VAS scores at the last follow-up of the three groups decreased(P<0.05),and the VAS score of the posterior group was lower(P<0.05).Conclusion The effects of anterior surgery,posterior surgery and anterior and posterior combined surgery in the treatment of elderly lumbar tuberculosis are good,and the approach method can be scientifically and reasonably formulated according to patients' physical condition to improve the clinical treatment effect.

The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.