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.

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 This study aims to explore the layout and optimization of management disciplines in"Double First-Class"Traditional Chinese Medicine(TCM)universities,providing talent support and management guidance for the devel-opment of TCM.Methods Based on an overview of the development of management disciplines in TCM universities,six"Doub-le First-Class"TCM universities were selected as research subjects.Data were collected and compared using web retrieval and lit-erature research methods.Results Management disciplines in TCM universities still face challenges,such as weak foundational infrastructure and difficulties in interdisciplinary integration,insufficient faculty and suboptimal curriculum systems,and a single teaching model with a disconnect between theory and practice.Conclusion This paper proposes targeted suggestions and strate-gies for optimizing the layout of management disciplines in TCM universities,including strengthening support for management dis-ciplines and deepening TCM management characteristics,optimizing curriculum design and enhancing faculty resources,and in-novating teaching models to promote the deep integration of theory and practice.

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 analyse the characteristics and development of oral mucosal diseases trials registered in the Chinese Clini-cal Trial Registry(ChiCTR).Methods:The ChiCTR database was searched to collect all studies related to oral mucosal diseases from July 25,2007 to September 30,2022.Statistical analysis was conducted on the names of oral mucosal diseases,registration dates,ge-ographical distribution,registration status,ethics committee approval,funding source,sample size,study type and design and blind-ing method.Results:312 registered studies related to oral mucosal diseases were collected.The diseases were mainly herpes zoster,hand-foot-and-mouth disease,radiotherapy-induced oral mucositis,pemphigus and oral lichen planus.The number of registered pro-jects basically showed an increasing trend.The institutions involved in the implementation of the study were mainly located in Beijing,Sichuan,Shanghai,Guangdong and Jiangsu,accounting for 55.02％of the total(340/618).The top 5 provinces and cities in terms of number of registered projects were Beijing,Sichuan,Jiangsu,Shanghai and Guangdong,accounting for 62.5％of the total included trials(195/312).Single-centre studies accounted for 77.56％(242/312),259 studies(83.01％)were pre-registered and 53(16.99％)were supplementary registrations,262(83.97％)studies were approved by the ethics committee.284 studies(91.03％)had their funding status marked,and a total of 301 grants were received,of which the top 3 were 31.89％(96/301)and were self-funded,23.26％(70/301)were funded by hospitals and 19.93％(60/301)were funded by local governments.The types of studies were mainly interventional studies 67.31％(210/312),followed by observational studies 17.31％(54/312).The research designs were mainly randomized parallel controlled trials,accounting for 63.14％(197/312),of which only 52(26.4％)studies explicitly stated the use of blinding,and 137(69.54％)studies were unspecified or blank in the blinding section.Conclusion:The studies on oral mucosal diseases registered in ChiCTR shows a trend of increasing year by year,the regional distribution is uneven,the number of multi-centre clinical trials is relatively small,and there is still room for improvement in study design and the application of blind ness method.

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

Objective:To analyse the characteristics and development of oral mucosal diseases trials registered in the Chinese Clini-cal Trial Registry(ChiCTR).Methods:The ChiCTR database was searched to collect all studies related to oral mucosal diseases from July 25,2007 to September 30,2022.Statistical analysis was conducted on the names of oral mucosal diseases,registration dates,ge-ographical distribution,registration status,ethics committee approval,funding source,sample size,study type and design and blind-ing method.Results:312 registered studies related to oral mucosal diseases were collected.The diseases were mainly herpes zoster,hand-foot-and-mouth disease,radiotherapy-induced oral mucositis,pemphigus and oral lichen planus.The number of registered pro-jects basically showed an increasing trend.The institutions involved in the implementation of the study were mainly located in Beijing,Sichuan,Shanghai,Guangdong and Jiangsu,accounting for 55.02％of the total(340/618).The top 5 provinces and cities in terms of number of registered projects were Beijing,Sichuan,Jiangsu,Shanghai and Guangdong,accounting for 62.5％of the total included trials(195/312).Single-centre studies accounted for 77.56％(242/312),259 studies(83.01％)were pre-registered and 53(16.99％)were supplementary registrations,262(83.97％)studies were approved by the ethics committee.284 studies(91.03％)had their funding status marked,and a total of 301 grants were received,of which the top 3 were 31.89％(96/301)and were self-funded,23.26％(70/301)were funded by hospitals and 19.93％(60/301)were funded by local governments.The types of studies were mainly interventional studies 67.31％(210/312),followed by observational studies 17.31％(54/312).The research designs were mainly randomized parallel controlled trials,accounting for 63.14％(197/312),of which only 52(26.4％)studies explicitly stated the use of blinding,and 137(69.54％)studies were unspecified or blank in the blinding section.Conclusion:The studies on oral mucosal diseases registered in ChiCTR shows a trend of increasing year by year,the regional distribution is uneven,the number of multi-centre clinical trials is relatively small,and there is still room for improvement in study design and the application of blind ness method.

During transfer tasks, the dual-arm nursing-care robot require a human-robot mechanics model to determine the balance region to support the patient safely and stably. Previous studies utilized human-robot two-dimensional static equilibrium models, ignoring the human body volume and muscle torques, which decreased model accuracy and confined the robot ability to adjust the patient's posture in three-dimensional spatial. Therefore, this study proposes a three-dimensional spatial mechanics modeling method based on individualized human musculoskeletal multibody dynamics. Firstly, based on the mechanical features of dual-arm support, this study constructed a foundational three-dimensional human-robot mechanics model including body posture, contact position and body force. With the computed tomography data from subjects, a three-dimensional femur-pelvis-sacrum model was reconstructed, and the individualized musculoskeletal dynamics was analyzed using the ergonomics software, which derived the human joint forces and completed the mechanic model. Then, this study established a dual-arm robot transfer platform to conduct subject transfer experiments, showing that the constructed mechanics model possessed higher accuracy than previous methods. In summary, this study provides a three-dimensional human-robot mechanics model adapting to individual transfers, which has potential application in various scenarios such as nursing-care and rehabilitating robots.
Humans ; Robotics ; Biomechanical Phenomena ; Posture ; Imaging, Three-Dimensional ; Nursing Care