Purpose: Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress. Materials and Methods: Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines in vitro, in breast cancer cell xenografts in vivo, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double-stranded DNA damages, respectively. Results: Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7–dependent apoptosis. Furthermore, the increase in sub-G1 population in the fluorescence-activated cell sorting analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single-stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in in vivo xenograft and patient-derived xenograft models. Conclusion Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder, with increasing prevalence due to obesity and lifestyle changes. Although proton pump inhibitors (PPIs) remain the first-line therapy, a proportion of patients have an unsatisfactory response, require long-term medication, or experience symptom relapse after discontinuation. Positioned between pharmacotherapy and surgery as a third therapeutic option, endoscopic therapy offers an additional choice for patients with refractory GERD. Based on current evidence, this article examines the optimal timing of endoscopic intervention, with particular attention to intervention after PPI failure, indications for endoscopic therapy, and individualized strategies for special populations. It also summarizes limitations of the existing evidence and outlines priorities for future research, including the need for long-term follow-up, robust cost-effectiveness evaluation, and exploration of biomarkers to inform timing decisions. In summary, evidence-based and individualized selection of intervention timing is essential to optimize the therapeutic efficacy of endoscopic management for GERD.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder, with increasing prevalence due to obesity and lifestyle changes. Although proton pump inhibitors (PPIs) remain the first-line therapy, a proportion of patients have an unsatisfactory response, require long-term medication, or experience symptom relapse after discontinuation. Positioned between pharmacotherapy and surgery as a third therapeutic option, endoscopic therapy offers an additional choice for patients with refractory GERD. Based on current evidence, this article examines the optimal timing of endoscopic intervention, with particular attention to intervention after PPI failure, indications for endoscopic therapy, and individualized strategies for special populations. It also summarizes limitations of the existing evidence and outlines priorities for future research, including the need for long-term follow-up, robust cost-effectiveness evaluation, and exploration of biomarkers to inform timing decisions. In summary, evidence-based and individualized selection of intervention timing is essential to optimize the therapeutic efficacy of endoscopic management for GERD.

Objective:To explore the repair methods and effects of refractory wounds in patients after spinal internal fixation operation .Methods:The study was a retrospective observational study. From November 2020 to October 2023, 10 patients with refractory wounds after spinal internal fixation operation were admitted to the Department of Burns and Plastic Surgery of Changde Hospital of Xiangya School of Medicine of Central South University. They were 3 males and 7 females, aged 35 to 68 years. There were 6 cases of thoracolumbar tuberculosis, 3 cases of thoracolumbar fracture, and 1 case of recurrent sacrococcygeal chordoma with skin, soft tissue, and bone defects after radical resection. The wound areas after debridement were 6.0 cm×1.5 cm to 27.0 cm×6.5 cm. The wound repair operation was decided to perform in the primary stage or in the secondary stage according to the wound situation. Two patients with type Ⅰ wounds were treated with debridement, direct suture, and continuous irrigation and drainage with catheter after operation. Eight patients with type Ⅱ wounds were repaired with local flaps (including rotation flap with dermis-fat flap at the end), muscle flaps, or muscle flaps combined with local flaps. The flap sizes were 10.0 cm×5.0 cm to 27.0 cm×14.0 cm, and the sizes of muscle flap were 8.0 cm×5.0 cm×4.0 cm to 17.0 cm×9.5 cm×2.0 cm. The wounds in flap donor areas were sutured directly. The wound treatment methods of patients with type Ⅱ wounds were recorded. The wound healing was observed after operation. The infection and recurrence of wounds, the retention of internal fixation materials, and spinal motor function were observed during follow-up.Results:Among patients with type Ⅱ wounds, there were 3 cases applied with local flaps (including 1 case with rotation flap with dermis-fat flap at the end), 3 cases with muscle flaps (including 1 case with latissimus dorsi muscle flap and 2 cases with erector spinal muscle flaps), and 2 cases with muscle flaps (1 case with latissimus dorsi muscle flap and 1 case with erector spinal muscle flap) combined with local flaps. Only 1 case with secondary defects after radical surgery of sacrococcygeal chordoma had poor wound healing which healed after dressing change, and the wounds of the remaining 9 cases all healed well. During the follow-up of 4 to 18 months, no infection or recurrence of local wounds developed in 10 patients, the internal fixation materials were not loosening, and there was no significant limitation in spinal motor function.Conclusions:For refractory wounds after spinal internal fixation operation, according to the wound type of patients, debridement, suture, irrigation, and drainage in the primary stage, or transplantation of local flaps, muscle flaps, muscle flaps combined with local flaps are performed in the primary stage or in the secondary stage. These methods are proved to have reliable therapeutic effects, not only repairing the wounds, but also retaining the internal fixation materials.

BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.

Objective:To explore the strategy of how to select an effective flap for reconstruction of the surgical defect in clavicular region after resection of malignant tumour and care for the aesthetic appearance of the flap donor site.Methods:A retrospective observational study was conducted. Twenty-three patients with soft tissue malignant tumour in clavicle region were treated, from March 2017 to April 2023, in the Department of Burn and Plastic Surgery of Changde Hospital, Xiangya School of Medicine, Central South University (the First People’s Hospital of Changde). The patients were 13 males and 10 females, aged 21 to 72 years old. Ten patients were of dermatofibrosarcoma protuberans, 6 of fibrosarcoma, 3 of squamous cell carcinoma of skin, 3 of undifferentiated pleomorphic sarcoma and 1 of mucinous adenocarcinoma. Nine patients had the first surgery and 14 were with tumour recurrence and had previousely received one or more surgery in other hospitals. The tumour size ranged from 2.0 cm×4.5 cm×1.0 cm to 10.0 cm×16.0 cm×3.0 cm. After radical resection, the sizes of surgical defect ranged from 9.0 cm×12.0 cm to 16.0 cm×22.0 cm. All the clavicular soft tissue malignancies had radical resection, and the secondary surgical defects were further modified to reduce the short and long dimensions of the defects. Flaps were selected according to the short dimension, depth and skin elasticity of the flap donor site. Of the 23 patients, 3 were treated with free inguinal flaps, 9 with ipsilateral pedicled latissimus dorsi flaps or thoracodorsal artery perforator flaps, 5 with free deep inferior epigastric artery perforator flap (DIEPF), 5 with free anterolateral thigh flap (ALTF) and 1 with free rectus abdominis flap. The modified defects sized 5.0 cm × 11.0 cm-12.0 cm×19.0 cm after the suture of margin and base of the defects (defects were reduced and modified). The flap sizes were 7.0 cm×13.0 cm-14.0 cm×23.0 cm. After surgery, the wound healing was observed through the visits of outpatient clinic, and telephone and WeChat interviews. According to the nature of the tumours, the patients were regularly reviewed at outpatient clinic to determine the local recurrence and metastasis of the tumour.Results:One pedicled latissimus dorsi myocutaneous flap was found with a greater tension after surgery. After partial removal of sutures and dressing changes, the secondary suture was performed 1 week later and the wound healed smoothly. A postoperative venous crisis was discovered in a free ALTF. It was monitored and re-anastomosed within 24 hours after surgery, and the flap survived and the wound healed smoothly. Otherwise, the rest of flaps achieved good blood supply and the wounds at the recipient and donor sites healed in one stage. In the postoperative follow-up, all flaps in the clavicular region were found good in appearance with no obvious swelling, and the donor sites healed well without scar contracture or dysfunction. One patient with a squamous cell carcinoma died of lung metastasis at 13 months after surgery. The rest of patients were found no tumour recurrence and had completed postoperative follow-up.Conclusion:After radical resection of malignant soft tissue tumours in the clavicular region, appropriate flaps were selected according to the size (short diameter) and depth of the modified defects, as well as the skin elasticity and relaxation of the flap donor site, hence to facilitate the direct suture of the flap donor site. It not only effectively reconstructs the surgical defect in clavicular region, but also minimises the damage to the flap donor site and achieves an aesthetic appearance at the flap donor site.

The abnormal accumulation of extracellular matrix (ECM) in liver is the main feature of hepatic fibrosis,and collagen is the most important component in ECM.Collagen plays an important role in the occurrence and development of liver fibrosis.Therefore,to find traditional Chinese medicine with significant effect on collagen metabolism has become a critical approach for the treatment of hepatic fibrosis.This review summarized the role of collagen metabolism in liver fibrosis,and the research progress in traditional Chinese medicines with anti-hepatic fibrosis effect by regulating collagen metabolism was explored as well.

Objective To know the cause for contamination of drinking water in a hotel. Methods Samples were taken from the reservoir 1 h, 14 h, 22 h and 33 h after contamination and the perceptible character, chemical and bacteriological test were done by using the methods in Analytical Methods for Water and Sanitary Standard for Drinking Water Quality(2001). Results The turbidity increased at 14 h after contamination and the highest level reached 3.82 NTU. The residual chlorine in tap water from the reservoir was less than 0.05 mg/L, the total count of bacteria was 940 cfu/ml, the total coliform bacteria was more than 1 600 MPN/100 ml and fecal coliforms was 130 MPN/100 ml. Conclusion The contamination of drinking water in the investigated hotel is caused by drinking water reservoir leakage, so more attention must be paid to the contamination of drinking water reservoir.