Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective To investigate the current status of frailty in patients on maintenance hemodialysis(MHD),and explore the correlation of frailty with anxiety and depression.Methods General information,clinical data and blood biochemical data of 101 cases who underwent MHD in Department of Nephrology,Shunde Hospital Affiliated to Jinan University from January 2023 to January 2024 were collected.FRAIL scale was applied to evaluate the frailty of the patients,and they were accordingly classified into frailty group and non-frailty group(including pre-frail and non-frail participants).Anxiety and depression were evaluated by GAD-7 and PHQ-9 scale.Univariate analysis and logistic regression were used to explore the association of frailty with anxiety,depression and other possible influencing factors.Results Among the 101 cases,29 cases(28.71%)were includedin frailty group and 72 cases(71.29%)in non-frailty group.There were 42 patients with depression(41.58%)and 25 with anxiety(24.75%).In the frailty group,the prevalence of depression was 65.52%and that of anxiety 55.17%.There were significant differences in age,grip strength,exercise,stroke and coronary heart disease,anxiety and depression,ferritin and CRP between the two groups(P＜0.01).Multivariate regression analysis showed that depression,anxi-ety,no exercise,stroke and high ferritin concentration were independent risk factors for frailty in MHD patients(P＜0.05).Conclusion In patients on MHD,frailty is closely associated with depression,anxiety,and lack of exercise,and stroke as well as high ferritin concentration are independent risk factors for frailty.

As a novel star molecule, gasdermin D (GSDMD) plays an important role in the amplification of immune inflammatory response and the process of pyroptosis. After being cleaved and activated by caspase-1, the N-terminal of GSDMD is rapidly released, which anchors on the cell membrane and forms pores, thereby leading to pyroptosis, accompanied by the release of a large amount of the strong proinflammatory factors IL-1β and IL-18. Acute/chronic liver inflammatory response and cell death are the common pathological features of liver diseases such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, liver failure, and hepatocellular carcinoma. This article summarizes the basic structural characteristics of GSDMD and elaborates on its important role in the pathological progression of various liver diseases. In addition, it is proposed that prevention and treatment strategies with GSDMD as a potential therapeutic target can provide new ideas for further studies on the clinical prevention and treatment of liver diseases.

Objective To understand the health-related quality of life (HRQOL) of migrant workers with pneumoconiosis who received basic medical treatment in Hunan Province. Methods A total of 613 migrant workers with pneumoconiosis who received basic medical treatment and assistance in Hunan Province was selected as the study subjects using stratified random sampling method. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to assess their HRQOL. Results The abnormality of the five dimensions of the EQ-5D health description system, from high to low, were as follows： daily activities, mobility, pain/discomfort, anxiety/depression, and self-care, with the abnormal rates of 50.9%, 46.8%, 41.1%, 21.0%, and 14.5%, respectively. The visual analogue scale (VAS) score of EQ-5D was (63.5±18.6) points. Patients with stage Ⅲ pneumoconiosis had high abnormality in mobility, daily activities, and pain/discomfort compared with those with stage Ⅰ and Ⅱ disease (all P<0.02). Patients in stage Ⅱ and Ⅲ of pneumoconiosis had higher incidence of anxiety/depression compared with those with stage I disease (all P<0.02). Patients with complications in addition to pneumoconiosis had higher abnormality in mobility, self-care, and pain/discomfort compared to those with simple pneumoconiosis or those eligible for lung lavage treatment (all P<0.02). Patients with simple pneumoconiosis had a higher incidence of anxiety/depression compared with those eligible for lung lavage treatment (P<0.02). Patients with stage Ⅲ pneumoconiosis had lower average VAS scores compared with stage Ⅰ and Ⅱ patients (all P<0.02). Patients with simple pneumoconiosis or those with complications had lower average VAS scores compared with those eligible for lung lavage treatment (all P<0.05). Conclusion The HRQOL of pneumoconiosis patients among migrant workers needs improvement, especially for patients with stage Ⅲ disease and those with complications. This study indicates the need of optimizing policies, raising the hospitalization expense limit for critically ill patients with stage Ⅲ pneumoconiosis or with complications, and improving their HRQOL.

Objective:To explore clinical application value of immediate breast reconstruction with silicone prosthesis after nipple areolar sparing mastectomy for breast cancer.Methods:The clinical data of 30 breast cancer patients underwent immediate breast reconstruction with the silicone prosthesis after nipple areolar sparing mastectomy from January 2016 to January 2018 were collected. In the observation group, 15 patients underwent immediate breast reconstruction with the silicone prosthesis after nipple areolar sparing mastectomy. In the control group, 15 patients underwent conventional modified radical mastectomy only. The differences of operation indicator and postoperative complications between the two groups were compared, and the postoperative cosmetic effects were evaluated.Results:The patients successfully completed prosthetic breast reconstruction in the observation group. The surgical time and indwelling time of the drainage tube in the observation group were both increased compared with the control group, and the difference was statistically significant ( t=118.8 and t=23.9, P<0.05). There were no statistically significant differences between the two groups in the complications of postoperative flap necrosis, subcutaneous hematoma, intraoperative infection and incision dehiscence ( P>0.05). The total complications rate of the observation group was 40%, compared with the control group (20%), there were not statistically significant differences ( P>0.05). The postoperative aesthetic effect evaluation showed that the reconstructed breast was full in shape and basically symmetrical to the contralateral side, with an excellent and good rate of 83.3%. The patients were satisfied with the appearance of the breast. All patients were followed up for 12 to 36 months with the average time of 24 months, and local recurrence and distant metastasis were not observed. Conclusions:In the modified radical mastectomy for breast cancer with preserved nipple and areola, the immediate application of silicone prosthesis for breast reconstruction has the advantages of less trauma, faster postoperative recovery and better cosmetic effect, which is worthy of clinical application.

Objective:To analyze the epidemiological characteristics of pneumoconiosis in Hunan Province.Methods:In November 2018, we collected the type of work, pneumoconiosis type, pneumoconiosis stage, length of service, age of onset and complications of pneumoconiosis cases diagnosed by Hunan occupational disease prevention and control hospital from January 2017 to October 2018. A total of 3 325 cases of pneumoconiosis were collected, including 651 cases (19.58%) of occupational pneumoconiosis and 2674 cases (80.42%) of clinically diagnosed pneumoconiosis. The measurement data were expressed by ± s. The comparison between groups was performed by independent sample t test and one-way ANOVA. Results:The age of 651 patients with occupational pneumoconiosis was 35.59-85.15 years old, the average age of onset was (54.27±8.29) years, and the average exposure to dust was (14.74±8.60) years. 2 674 cases of clinically diagnosed pneumoconiosis were 26.85~87.02 years old. The average age of onset was (55.26±7.38) years, and the average exposure time was (18.83±9.35) years. Compared with silicosis patients, coal workers' pneumoconiosis patients had longer exposure time, the difference was statistically significant ( P<0.05) , and the difference was statistically significant ( F=3.678, P<0.05) . There were no complications in 651 cases of occupational pneumoconiosis. Among 2 674 cases of clinically diagnosed pneumoconiosis, 710 cases (26.55%) had complications. Conclusion:Further attention should be paid to the clinical diagnosis of pneumoconiosis in Hunan Province.

Objective:To analyze the epidemiological characteristics of pneumoconiosis in Hunan Province.Methods:In November 2018, we collected the type of work, pneumoconiosis type, pneumoconiosis stage, length of service, age of onset and complications of pneumoconiosis cases diagnosed by Hunan occupational disease prevention and control hospital from January 2017 to October 2018. A total of 3 325 cases of pneumoconiosis were collected, including 651 cases (19.58%) of occupational pneumoconiosis and 2674 cases (80.42%) of clinically diagnosed pneumoconiosis. The measurement data were expressed by ± s. The comparison between groups was performed by independent sample t test and one-way ANOVA. Results:The age of 651 patients with occupational pneumoconiosis was 35.59-85.15 years old, the average age of onset was (54.27±8.29) years, and the average exposure to dust was (14.74±8.60) years. 2 674 cases of clinically diagnosed pneumoconiosis were 26.85~87.02 years old. The average age of onset was (55.26±7.38) years, and the average exposure time was (18.83±9.35) years. Compared with silicosis patients, coal workers' pneumoconiosis patients had longer exposure time, the difference was statistically significant ( P<0.05) , and the difference was statistically significant ( F=3.678, P<0.05) . There were no complications in 651 cases of occupational pneumoconiosis. Among 2 674 cases of clinically diagnosed pneumoconiosis, 710 cases (26.55%) had complications. Conclusion:Further attention should be paid to the clinical diagnosis of pneumoconiosis in Hunan Province.

Objective To evaluate and compare the short-term effects of two kinds of plastic mulch on Oncomelania hupensis snail control in irrigation and drainage ditches with snails in Yunnan Province. Methods The irrigation and drainage ditches with high density of Oncomelania hupensis snails were chosen as the investigation sites,and then 4 groups were set,namely a colorless plastic mulch group,black plastic mulch group,colorless plastic mulch with molluscicide group and black plastic mulch with molluscicide group. The snail situation of the 4 groups was surveyed before the experiment and 7,14,21,30 days after covering plastic mulch,and the snail death rates were compared among the 4 groups. Meanwhile,the hourly temperatures of soil surface,soil surface under plastic mulch and soil layer 5,15 cm under the surface as well as the weather situation during the study period were measured and recorded. Results The average snail mortality rate of the colorless plastic mulch group was only 15.29% that was higher than that of the black plastic mulch group(6.56%)(P < 0.01). The average snail mortality rates of the colorless and black plastic mulch with molluscicide groups were 40.80% and 50.15%,respectively,and there was no statis-tic difference between them(P > 0.05). Both kinds of plastic mulches could raise the temperature of the soil surface under plas-tic mulch and the soil layer below it,and the temperature of soil under the mulches increased over the cover time,and the aver-age temperature of the soil surface under the black mulch in 30 days was higher than that under the colorless mulch. Conclu-sion It is not suitable to use plastic mulch only in irrigation and drainage ditches with snails widely in Yunnan Province be-cause of its low effect,and if necessary,the molluscicide should be added.

OBJECTIVETo establish the technical specifications of transbronchoscope whole lung lavage (TBWLL) and to compare the clinical efficacy between TBWLL and bronchoalveolar lavage (BAL) or whole lung lavage (WLL).

METHODSA total of 133 patients with pneumoconiosis admitted to Hunan Prevention and Treatment Institute for Occupational Diseases from 2009 to 2014 were divided into TBWLL group (n=43), BAL group (n=45), and WLL group (n=45). Patients in the TBWLL group received conventional BAL of both lungs under a fiber bronchoscope, as well as sedation and anesthesia; lavage was performed twice in each course. TBWLL was compared with the BAL and WLL in terms of lavage volume. The clinical symptoms, pulmonary function, and blood gas before and after treatment and the safety were evaluated.

RESULTSThe TBWLL group had significantly relieved cough and limitation of activity after lavage (P<0.05). Compared with the BAL group, the TBWLL group had significantly increased single lavage volumes and total lavage volume and a significantly shortened length of hospital stay (P<0.05). The three groups showed no significant short-term changes in clinical symptoms and pulmonary function after lavage. The TBWLL and WLL groups had a significantly lower incidence of postoperative complications than the BAL group (P<0.05).

CONCLUSIONTBWLL has good clinical efficacy, with the advantages of BAL and WLL, and is highly feasible, safe, and effective.

BACKGROUND:The internal structures of the colagen-heparan sulfate scaffold and human nerve are very similar. OBJECTIVE: To explore thein vivo biocompatibility of colagen-heparin sulfate scaffold. METHODS:Forty pigs were randomly divided into two groups, 20 in each group: observation group and control group. Medulo-puncture needle was inserted 1.0 cm adjacent to the midline of anterior fontanele into the subarachnoid space, and then removed gradualy. Colagen-heparin sulfate scaffold was implanted into the observation group, and no treatment was given in the control group. Brain tissues were observed under transmission electron microscope, and cel apoptosis and Caspase-3 expression were detected at days 1, 3, 7, 14 and 30 after surgery. RESULTS AND CONCLUSION:Under the electron microscope, there were some damaged neurons in the observation group with the emergence of demyelination changes in the myelinated nerve fibers; positiveexpression of Caspase-3 protein was found at the junction between the brain tissue and scaffold as wel as within the scaffold, but no positive expression was found in the surrounding tissue. There was no cel apoptosis within 30 days after surgery except for individual apoptotic neurons both in the observation group and control group. The number of apoptotic cels in the observation group was higher than that in the control group at days 1, 3, 7, 14 days after surgery (P < 0.05), but there was no difference between the two groups at 30 days after surgery (P > 0.05). Caspase-3 protein expression was at a low state in the two groups, but the protein expression of Caspase-3 was higher in the observation group than the control group at days 3 and 7 after surgery (P < 0.05). These findings indicate that the colagen heparin sulfate scaffold has good biocompatibility in the porcine brain.