Objective The aim of this study was to analyze the incidence,mortality,and epidemiological trends of malignant tumors in the cancer registration areas of Qinghai Province and provide a reference for the prevention and control strategies and meas-ures of malignant tumors.Methods According to the quality control standards for cancer registration,the data on malignant tumor in-cidence and mortality from 8 national cancer registration areas in Qinghai Province from 2014 to 2021 were collated.The crude inci-dence/mortality,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and World standard population(ASIRW/ASMRW),the cumulative rates(0-74 years old),and the age-specific incidence/mortality of malignant tumors were calculated for different sexes and regions.The Joinpoint 4.9.0.0 software was used to calculate the average annual percentage change(AAPC)and conduct trend analysis.Results The crude incidence of malignant tumors in the cancer registration areas of Qinghai Province from 2014 to 2021 was 221.25/100,000(243.31/100,000 for males and 198.68/100,000 for females),the ASIRC was 199.48/100,000(229.13/100,000 for males and 173.34/100,000 for females),the ASIRW was 196.38/100,000(228.32/100,000 for males and 167.97/100,000 for females).The cumulative rate for those aged 0-74 years was 21.57％;the crude mortali-ty of malignant tumors was 131.90/100,000(163.86/100,000 for males and 99.20/100,000 for females),the ASMRC was 121.07/100,000(157.33/100,000 for males and 87.45/100,000 for females),the ASMRW was 120.53/100,000(157.54/100,000 for males and 86.31/100,000 for females),and the cumulative rate for those aged 0-74 years was 12.79％.The crude incidence,ASIRC,ASIRW,crude mortality,ASMRC and ASMRW were all higher in males than those in females.Both the crude incidence and mortality of malignant tumors increased with age.The crude incidence rate increased rapidly after age 45,peaked in the 80-84 age group(2,352.29 per 100,000),and declined slightly in the 85+age group.The crude mortality increased rapidly after age 50,peaked in the 85+age group(2,305.44 per 100,000).The crude incidence(AAPC=5.68％,95％CI:3.48％-7.93％,P＜0.05)and erude mortality(AAPC=3.67％,95％CI:2.44％-4.91％,P＜0.05)of malignant tumors showed an overall upward trend from 2014 to 2021.The ASIRC(AAPC=-0.12％,95％CI:-3.70％-3.59％,P＞0.05)remained stable,while the ASMRC(AAPC=-2.81％,95％CI:-3.28％--2.03％,P＜0.05)showed a downward trend.The top five malignant tumors in terms of crude incidence were stom-ach cancer,lung cancer,liver cancer,female breast cancer,and cervical cancer,respectively;the top five malignant tumors in terms of crude mortality were stomach cancer,lung cancer,liver cancer,esophagus cancer,and colorectal cancer,respectively.Conclusion From 2014 to 2021,the incidence and mortality of malignant tumors in the Qinghai Province cancerregistration areas showed an in-creasing trend,with higher rates in males than those in females.It is recommended that targeted prevention and control measures should be implemented for people aged 45 and older,with stomach cancer,liver cancer,and cervical cancer as key cancers.

Objective: To analyze the mediating effects of loneliness and depressive symptoms on family functioning and life satisfaction among rural elderly patients with chronic diseases, so as to provide the basis for improving the life satisfaction of this population. Methods: Rural elderly patients with chronic diseases aged ≥60 years in Qiannan Buyi and Miao Autonomous Prefecture, Guizhou Province were selected using a multi-stage stratified random cluster sampling method from June to September 2022. Basic information such as gender, age, and chronic diseases were collected. Family function, life satisfaction, loneliness and depressive symptoms were evaluated using Family Care Index Scale, the Satisfaction with Life Scale, the b-item Revised VCLA Loneliness Sale and the 15-item Geriatric Depression Scale, respectively. The structural equation model was constructed using Amos software to analyze the mediating effects of loneliness and depressive symptoms on the relationship between family function and life satisfaction. The Bootstrap method was employed to test the mediating effects. Results: A total of 1 145 rural elderly patients with chronic diseases were recruited, including 517 males (45.15%) and 628 females (54.85%). Among the participants, 657 individuals (57.38%) were aged 60-<71 years, and 540 individuals (47.16%) had three or more chronic diseases. The scores for family function, life satisfaction, loneliness, and depressive symptoms were (3.90±1.18), (18.88±5.25), (12.88±2.99), and (6.65±2.26), respectively. Mediating effect analysis showed that family function had a direct positive effect on life satisfaction (β=0.179, 95%CI: 0.126-0.231). It also indirectly positively influenced the life satisfaction of rural elderly patients with chronic diseases through the independent mediating effect of depressive symptoms (β=0.035, 95%CI: 0.021-0.054) and the chained mediating effect of loneliness and depressive symptoms (β=0.021, 95%CI: 0.013-0.030). The mediating effect of depressive symptoms accounted for 14.89% of the total effect, while the chained mediating effect of loneliness and depressive symptoms accounted for 8.94% of the total effect. Conclusion Good family function can directly enhance the life satisfaction of rural elderly patients with chronic diseases and can also indirectly improve their life satisfaction by reducing loneliness and depressive symptoms.

Objective The aim of this study was to analyze the incidence,mortality,and epidemiological trends of malignant tumors in the cancer registration areas of Qinghai Province and provide a reference for the prevention and control strategies and meas-ures of malignant tumors.Methods According to the quality control standards for cancer registration,the data on malignant tumor in-cidence and mortality from 8 national cancer registration areas in Qinghai Province from 2014 to 2021 were collated.The crude inci-dence/mortality,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and World standard population(ASIRW/ASMRW),the cumulative rates(0-74 years old),and the age-specific incidence/mortality of malignant tumors were calculated for different sexes and regions.The Joinpoint 4.9.0.0 software was used to calculate the average annual percentage change(AAPC)and conduct trend analysis.Results The crude incidence of malignant tumors in the cancer registration areas of Qinghai Province from 2014 to 2021 was 221.25/100,000(243.31/100,000 for males and 198.68/100,000 for females),the ASIRC was 199.48/100,000(229.13/100,000 for males and 173.34/100,000 for females),the ASIRW was 196.38/100,000(228.32/100,000 for males and 167.97/100,000 for females).The cumulative rate for those aged 0-74 years was 21.57％;the crude mortali-ty of malignant tumors was 131.90/100,000(163.86/100,000 for males and 99.20/100,000 for females),the ASMRC was 121.07/100,000(157.33/100,000 for males and 87.45/100,000 for females),the ASMRW was 120.53/100,000(157.54/100,000 for males and 86.31/100,000 for females),and the cumulative rate for those aged 0-74 years was 12.79％.The crude incidence,ASIRC,ASIRW,crude mortality,ASMRC and ASMRW were all higher in males than those in females.Both the crude incidence and mortality of malignant tumors increased with age.The crude incidence rate increased rapidly after age 45,peaked in the 80-84 age group(2,352.29 per 100,000),and declined slightly in the 85+age group.The crude mortality increased rapidly after age 50,peaked in the 85+age group(2,305.44 per 100,000).The crude incidence(AAPC=5.68％,95％CI:3.48％-7.93％,P＜0.05)and erude mortality(AAPC=3.67％,95％CI:2.44％-4.91％,P＜0.05)of malignant tumors showed an overall upward trend from 2014 to 2021.The ASIRC(AAPC=-0.12％,95％CI:-3.70％-3.59％,P＞0.05)remained stable,while the ASMRC(AAPC=-2.81％,95％CI:-3.28％--2.03％,P＜0.05)showed a downward trend.The top five malignant tumors in terms of crude incidence were stom-ach cancer,lung cancer,liver cancer,female breast cancer,and cervical cancer,respectively;the top five malignant tumors in terms of crude mortality were stomach cancer,lung cancer,liver cancer,esophagus cancer,and colorectal cancer,respectively.Conclusion From 2014 to 2021,the incidence and mortality of malignant tumors in the Qinghai Province cancerregistration areas showed an in-creasing trend,with higher rates in males than those in females.It is recommended that targeted prevention and control measures should be implemented for people aged 45 and older,with stomach cancer,liver cancer,and cervical cancer as key cancers.

Objective:To analyze the clinical and pathological data of 15 patients with light chain amyloidosis initially diagnosed with other kidney diseases, and identify possible misdiagnosis reasons.Methods:It was a retrospective observational study. The clinical and pathological data of 15 patients, whose initial kidney biopsies failed to diagnose light chain-amyloidosis but were confirmed by a subsequent kidney biopsy or pathology consultation at Peking University First Hospital from January 2010 to December 2022 were collected. The results of immunofluorescence, Congo red staining, and electron microscopy of two renal biopsies were analyzed.Results:The median age of 15 patients was 56 years old, with a male-to-female ratio of 7∶8. The main clinical manifestation was massive proteinuria with normal kidney function, and there were 10 cases presenting as nephrotic syndrome. The initial diagnosis based on the first kidney biopsy included minimal change disease (8 cases), IgA nephropathy (3 cases), membranous nephropathy (3 cases), and type Ⅲ collagen glomerulonephritis (1 case). M proteinemia was not evaluated in 13 patients during the first kidney biopsy. Light chain immunofluorescence staining was not performed in 12 cases. Congo red staining was not performed in 13 cases. All fifteen patients received glucocorticoids combined with immunosuppressive therapy after their initial diagnosis, and 5 patients developed severe infection. After 12.0 (7.5, 20.0) months of treatment, none of them achieved clinical remission. Thirteen had evidences for M protein before the second kidney biopsy. The renal tissues of all patients underwent immunofluorescence light chain examination, Congo red staining, and immunoelectron microscopy examination when necessary. The repeat kidney biopsies of 14 cases and pathology consultation of one case consistently indicated light chain-amyloidosis. The kidney tissues in 13 cases were confirmed to be light chain restricted, 11 cases by immunofluorescence, and 2 cases by immune electron microscopy. After diagnosis of light chain-amyloidosis, all patients received targeted plasma cell therapy except for 1 patient lost to follow-up, 6 patients achieved hematologic remission, 5 patients achieved renal remission, 1 patient entered end-stage renal disease, and 3 patients died.Conclusions:In middle and elderly-aged patients with nephrotic syndrome, if conventional immunosuppressive therapy yields unsatisfactory results, it is crucial to focus on identifying evidences of monoclonal immunoglobulinemia, if necessary, kidney biopsy should be actively repeated. Kidney biopsy pathology should include comprehensive examinations such as light chain immunofluorescence, Congo red staining, and electron microscopy to avoid misdiagnosis of light chain-amyloidosis.

The paper reports a case of coenzyme Q10 deficiency nephrotic syndrome associated with coenzyme Q2 gene mutation and reviews the literature on this topic. The patient presented with hematuria, proteinuria, and a diminution of vision as clinical manifestations. But the proteinuria was not relieved after sufficient doses of glucocorticoids for over 2 months. The patient′s birth history was unremarkable, and his parents were both healthy and not consanguineous. Whole exome sequencing revealed that the patient had a mutation of coenzyme Q2 gene at c.973A>G(p.T325A) and c.517C>T(p.R173C). Combined with renal biopsy pathology, the patient was diagnosed with hereditary nephropathy and started the supplements of coenzyme Q10 after stopping glucocorticoid treatments immediately. After 5 weeks of therapy, the patient′s 24-h urine protein quantification decreased from 6.01 g to 1.53 g.

Objective:To summarize and analyze the clinicopathological characteristics of patients with DNAJ heat shock protein family member B9 (DNAJB9)-positive fibrillary glomerulonephritis (FGN).Methods:The clinical and pathological data of 5 patients with DNAJB9-positive FGN diagnosed in Peking University First Hospital from January 2011 to January 2021 were retrospectively collected and analyzed.Results:Among the 5 patients, the female to male ratio was 4∶1, and the median age was 29 years old (24-71 years old). The clinical manifestations included 2 cases with nephrotic syndrome and 3 cases with proteinuria. One patient had gross hematuria, and 4 cases had mild microscopic hematuria. None of the 5 patients had evidence of monoclonal gammopathy. The renal pathological pattern of FGN showed mesangial-proliferative glomerulonephritis, mesangial nodular sclerosis, membranoproliferative glomerulonephritis, and atypical membranous nephropathy. Crescents formation could be accompanied. Immunofluorescence staining showed smudgy and granular IgG and C3 deposition in the mesangial region and capillary wall, and the subtypes of IgG were mainly IgG1 and IgG4. Under electron microscopy, fibrillary deposits with a diameter of 8-30 nm were observed in the mesangial and subendothelial area, accompanied by deposition in basement membrane and occasionally subepithelial area. The renal prognosis of FGN patients was poor. One patient entered end-stage renal disease within one week, and another patient entered end-stage renal disease within one year despite immunosuppressant therapy in 2 cases with nephrotic syndrome at onset. One patient had worsening proteinuria despite renin-angiotensin system (RAS) blocker treatment. Two patients achieved complete renal remission and stable renal function after RAS blocker treatment.Conclusions:Most FGN patients in China are young people. The main clinical manifestations are proteinuria or mild microscopic hematuria. The diagnosis depends on the discovery of fibrillary deposits in the mesangial area and subendothelial area with a diameter of about 10-30 nm under the electron microscope. DNAJB9 protein immunohistochemical staining can be used as an important marker for the diagnosis of FGN. The prognosis of FGN kidney is poor, and there is no effective targeted treatment option now.

Objective:To investigate the clinicopathological characteristics of renal leukocyte chemotactic factor 2 amyloidosis (ALECT2).Methods:The patients with renal ALECT2 diagnosed by renal biopsy in Peking University First Hospital, Shanxi Medical University Second Hospital and Shanxi Bethune Hospital from January 2001 to October 2021 were retrospectively enrolled. According to whether the patients had concurrent glomerular diseases, they were classified into two groups: isolated ALECT2 group and ALECT2 with concurrent renal diseases group. Clinicopathological data of the two groups were compared. Light microscopy, immunofluorescence and immunoelectron microscopy were applied to investigate pathological characteristics of renal tissues. Mass spectrometry was used to analyze the composition of renal amyloid deposits. Gene sequencing was employed to detect the leukocyte chemotactic factor 2 ( LECT2) gene sequence in peripheral blood of the patients. Results:Sixteen patients with ALECT2 were enrolled in this study and nine of them had concurrent renal diseases. The age of 16 patients was (65.00±8.45) years old. The sex ratio of males to females was 7 to 9. Most of patients were Han ethnicity (15/16). Eight patients came from Shanxi province. Fifteen patients presented with varying degree of proteinuria [2.16(1.07, 4.72) g/24 h]; 5 patients had nephrotic syndrome; 11 patients had renal insufficiency; 12 patients had microscopic hematuria. Part of patients also had hypertension (12/16) and diabetics (6/16). Compared with isolated ALECT2, the ALECT2 group with concurrent renal diseases had a higher proportion of nephrotic syndrome (5/9 vs 0/7, P=0.034). Renal biopsy results showed that all patients (16/16) had amyloid deposits in the interstitium of renal cortex with varying degree of inflammatory cell infiltration and fibrosis, and glomeruli (12/16) and arterioles (14/16) were involved by amyloid deposits. The amyloid deposits were strongly congophilic and immunohistochemistry for LECT2 was positive. By semi-quantitative analysis, the proportions of glomerular and overall amyloid loads in ALECT2 with concurrent renal diseases group were lower than those in isolated ALECT2 group (both P<0.05). Electron microscopy revealed randomly oriented and non-branching fibrils with a diameter of 8-12 nm. The LECT2 peptides were detected by mass spectrometry in renal amyloid deposits of 8 patients, and homozygous G allele of LECT2 was found in 7 patients by gene sequencing. Complete follow-up data of 13 patients showed that 2 patients died, 1 patient developed end-stage renal disease at the time of renal biopsy, and most of the rest patients had stable renal function (8/10). Conclusions:Patients with renal ALECT2 mainly present with proteinuria, along with a high incidence of renal insufficiency, microscopic hematuria, and concurrent renal diseases. The pathologic feature is the preferential deposition of amyloid in renal cortical interstitium.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective:To explore effects of family medical information management platform on medication discrepancy, medication compliance and nutritional management of patients with colorectal cancer undergoing chemotherapy.Methods:Using the convenient sampling method, a total of 64 patients with colorectal cancer who received chemotherapy in Henan Provincial People's Hospital from March 2018 to June 2019 were selected as the research objects. According to the random number table method, they were divided into the control group and the observation group, with 32 cases in each group. The control group adopted conventional management, while the observation group adopted family medical information management platform. After intervention, Medication Discrepancy Tool (MDT) and the Chinese Version of Morisky Medication Compliance Scale were used to compare the incidence of medication discrepancy and medication compliance of patients of the two groups. The nutritional status of patients in the two groups was compared using BMI, hemoglobin, total protein, albumin and modified Subjective Global Assessment (SGA) scores.Results:After the intervention, the incidence of medication discrepancy in the observation group was 21.88% (7/32) , lower than 62.50% (20/32) in the control group, and the difference was statistically significant (χ 2=10.827, P<0.01) . After the intervention, there was a statistically significant difference in medication compliance between the two groups ( Z=2.207, P<0.05) . After intervention, BMI, hemoglobin, total protein and albumin of the observation group were higher than those of the control group, and the modified SGA score was lower than that of the control group, and the differences were statistically significant ( t=-2.340, -3.007, -2.137, -3.334, 3.107; P<0.05) . After intervention, the number of normal nutritional cases in the observation group was higher than that in the control group, and the number of severe malnutrition cases was lower than that in the control group, and the differences were statistically significant (χ 2=4.267, 5.379; P<0.05) . Conclusions:The application of family medical information management platform can reduce medication discrepancy of patients with colorectal cancer undergoing chemotherapy, improve their medication compliance and reduce the occurrence of malnutrition.