Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

Objective:To study the comprehensive surgical treatment of brucellosis with chest wall cysts as the main manifestation.Methods:Retrospective analysis was made on the general information epidemiological characteristics, clinical manifestations, laboratory examinations, imaging examinations, treatment and outcomes of five patients with brucellosis mainly manifested by chest wall cysts admitted to the 948 Hospital of the People's Liberation Army from July 2019 to June 2022.Results:Among the 5 patients, there were 4 males and 1 female, aged between 23 and 64 years old, with a clear history of contact with cattle and sheep. The main clinical manifestation was painless cystic masses on the chest wall. Both the serum tiger red plate agglutination test (RBPT) and the test tube agglutination test (SAT) were positive. Four cases were infected with Brucella and one case was infected with Actinobacillus pleuropneumoniae (considered as Brucella infection based on the overall condition). All patients exhibited abnormal chest wall signals (manifesting as hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging) on magnetic resonance imaging(MRI), and were ultimately diagnosed with brucellosis presenting predominantly as chest wall cysts. After complete removal of the chest wall cyst through surgery, a combination treatment of rifampicin capsules and doxycycline hyclate tablets was given for 6 weeks. There were no significant adverse reactions and the wound healed in one stage. During the postoperative follow-up period of 11 - 40 months, MRI reexamination demonstrated no evidence of chest wall cyst recurrence, and all SAT results were negative. Conclusions:Patients with brucellosis presenting as chest wall cysts are clinically rare and lack specific symptoms. Surgical resection of the affected lesion combined with early, standardized, combined, and full course antimicrobial therapy results in a good prognosis for the patient.

Objective:To study the comprehensive surgical treatment of brucellosis with chest wall cysts as the main manifestation.Methods:Retrospective analysis was made on the general information epidemiological characteristics, clinical manifestations, laboratory examinations, imaging examinations, treatment and outcomes of five patients with brucellosis mainly manifested by chest wall cysts admitted to the 948 Hospital of the People's Liberation Army from July 2019 to June 2022.Results:Among the 5 patients, there were 4 males and 1 female, aged between 23 and 64 years old, with a clear history of contact with cattle and sheep. The main clinical manifestation was painless cystic masses on the chest wall. Both the serum tiger red plate agglutination test (RBPT) and the test tube agglutination test (SAT) were positive. Four cases were infected with Brucella and one case was infected with Actinobacillus pleuropneumoniae (considered as Brucella infection based on the overall condition). All patients exhibited abnormal chest wall signals (manifesting as hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging) on magnetic resonance imaging(MRI), and were ultimately diagnosed with brucellosis presenting predominantly as chest wall cysts. After complete removal of the chest wall cyst through surgery, a combination treatment of rifampicin capsules and doxycycline hyclate tablets was given for 6 weeks. There were no significant adverse reactions and the wound healed in one stage. During the postoperative follow-up period of 11 - 40 months, MRI reexamination demonstrated no evidence of chest wall cyst recurrence, and all SAT results were negative. Conclusions:Patients with brucellosis presenting as chest wall cysts are clinically rare and lack specific symptoms. Surgical resection of the affected lesion combined with early, standardized, combined, and full course antimicrobial therapy results in a good prognosis for the patient.

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

Objective:To investigate the therapeutic effectiveness of double-anatomical plate-assisted reconstruction of a stable triangle in the treatment of chronic distal humerus fractures.Methods:A retrospective analysis was performed on the medical records of 10 patients with distal humerus fracture treated with double plate assisted reconstruction of a stable triangle from August 2021 to December 2024. All patients were followed up for more than 6 months. The cohort included 9 males and 1 female, with a mean age of 54.75±15.15 years (range, 31-73 years). Causes of injury: 4 cases of slip, 2 cases of high-energy fall, 3 cases of traffic accident, and 1 case of crush injury. According to the AO/OTA classification, all fractures were type C3, including 4 cases of C3.3 and 6 cases of C3.2. The operation duration, intraoperative blood loss, and length of hospital stay were recorded. Follow-up evaluations were conducted at 1, 3, and 6 months postoperatively and at the final follow-up. Radiographs were obtained to assess fracture reduction, healing, and implant positioning. Functional outcomes of the elbow were assessed using carrying angle, humeral condyle anteversion angle, modified trochleocapitellar index (mTCI), range of motion (ROM), visual analogue scale (VAS) for pain, Mayo elbow performance score (MEPS), and complication rates.Results:All 10 patients successfully completed the operation, with an average operation time of 221.75±48.73 min (range, 165-310 min), an average intraoperative blood loss of 462.50±215.05 ml (range 150-800 ml). 4 patients received blood transfusion. The average hospital stay was 10.75±2.55 d (range 6-14 d). The average carrying angle of 171.50°±5.37° (range 165°-179°) and the anterior angle of humeral condyle 39.75°±3.96° (range 34°-45°) were all within the standard range. At least one index in the mTCI was within the optimal range at the last follow-up. All patients were followed up with an average follow-up of 10.75±5.73 months (range 6-22 months). All 10 patients were healed after surgery with an average healing time of 4.75±2.05 months (range 3-9 months). At the final follow-up, the average elbow ROM was 93.75°±25.88° (range, 50°-115°), internal rotation was 83.13°±9.61° (range, 60°-90°), and external rotation was 88.13°±3.72° (range, 80°-90°). The mean VAS score was 0.63±0.92 (range, 0-2), and the average MEPS was 88.75±11.57 (range, 70-100), with 4 excellent, 4 good, and 2 fair outcomes, an excellent and good rate of 80%. Complications included one case of periarticular osteophyte formation, one case of transient ulnar nerve numbness that improved with conservative treatment, and three cases of occasional mild pain following increased activity. Conclusion Double-anatomical plate-assisted reconstruction of a stable triangle provides effective and stable fixation for chronic AO/OTA C3 distal humerus fractures. The short-term postoperative outcomes are satisfactory, with good functional recovery and a low complication rate.Conclusions:Double-anatomical plate-assisted reconstruction of a stable triangle provides effective and stable fixation for chronic AO/OTA C3 distal humerus fractures. The short-term postoperative outcomes are satisfactory, with good functional recovery and a low complication rate.

Objective:To investigate the therapeutic effectiveness of double-anatomical plate-assisted reconstruction of a stable triangle in the treatment of chronic distal humerus fractures.Methods:A retrospective analysis was performed on the medical records of 10 patients with distal humerus fracture treated with double plate assisted reconstruction of a stable triangle from August 2021 to December 2024. All patients were followed up for more than 6 months. The cohort included 9 males and 1 female, with a mean age of 54.75±15.15 years (range, 31-73 years). Causes of injury: 4 cases of slip, 2 cases of high-energy fall, 3 cases of traffic accident, and 1 case of crush injury. According to the AO/OTA classification, all fractures were type C3, including 4 cases of C3.3 and 6 cases of C3.2. The operation duration, intraoperative blood loss, and length of hospital stay were recorded. Follow-up evaluations were conducted at 1, 3, and 6 months postoperatively and at the final follow-up. Radiographs were obtained to assess fracture reduction, healing, and implant positioning. Functional outcomes of the elbow were assessed using carrying angle, humeral condyle anteversion angle, modified trochleocapitellar index (mTCI), range of motion (ROM), visual analogue scale (VAS) for pain, Mayo elbow performance score (MEPS), and complication rates.Results:All 10 patients successfully completed the operation, with an average operation time of 221.75±48.73 min (range, 165-310 min), an average intraoperative blood loss of 462.50±215.05 ml (range 150-800 ml). 4 patients received blood transfusion. The average hospital stay was 10.75±2.55 d (range 6-14 d). The average carrying angle of 171.50°±5.37° (range 165°-179°) and the anterior angle of humeral condyle 39.75°±3.96° (range 34°-45°) were all within the standard range. At least one index in the mTCI was within the optimal range at the last follow-up. All patients were followed up with an average follow-up of 10.75±5.73 months (range 6-22 months). All 10 patients were healed after surgery with an average healing time of 4.75±2.05 months (range 3-9 months). At the final follow-up, the average elbow ROM was 93.75°±25.88° (range, 50°-115°), internal rotation was 83.13°±9.61° (range, 60°-90°), and external rotation was 88.13°±3.72° (range, 80°-90°). The mean VAS score was 0.63±0.92 (range, 0-2), and the average MEPS was 88.75±11.57 (range, 70-100), with 4 excellent, 4 good, and 2 fair outcomes, an excellent and good rate of 80%. Complications included one case of periarticular osteophyte formation, one case of transient ulnar nerve numbness that improved with conservative treatment, and three cases of occasional mild pain following increased activity. Conclusion Double-anatomical plate-assisted reconstruction of a stable triangle provides effective and stable fixation for chronic AO/OTA C3 distal humerus fractures. The short-term postoperative outcomes are satisfactory, with good functional recovery and a low complication rate.Conclusions:Double-anatomical plate-assisted reconstruction of a stable triangle provides effective and stable fixation for chronic AO/OTA C3 distal humerus fractures. The short-term postoperative outcomes are satisfactory, with good functional recovery and a low complication rate.

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

Objective:To investigate the effect of Euphorbia Lathyrol on expressions of IL-7,IL-10 and VEGF in renal clear cell neoplasias(RCCN)mice by regulating TGF-β/Smad signaling pathway.Methods:RCCN xenograft mice were established and divided into model group,Euphorbia Lathyrol group and Cisplatin group.Euphorbia Lathyrol group were given 20 mg/kg Euphorbia Lathyrol solution intragastric administration,model group were given 0.9%NaCl gastric feeding,Cisplatin group were given intraperito-neal injection of 4 mg/kg cisplatin solution,then mice weight and tumor volume were recorded.Expressions of TGF-β1,Smad2 and Smad4 were tracked down through Western blot.Expressions of immune factors IL-7 and IL-10 in serum of xenograft mice were detected by ELISA.Expression of VEGF in tumor mass was detected by IHC.Results:After 14 days of administration,compared with model group,the proliferation of tumor grafts in Cisplatin group and Euphorbia Lathyrol group was inhibited(P<0.05),and the expressions of TGF-β1,Smad2,Smad4 protein and VEGF were observably decreased(P<0.05),expressions of IL-7 in serum was increased,while level of IL-10 in serum was decreased(P<0.05).Conclusion:Euphorbia Lathyrol is able to reduce expressions of IL-7,IL-10,as well as VEGF in RCCN xenograft mice by impeding TGF-β1/Smad signaling transduction system.