Disease In Tibet Research Articles

Detection and Significance of Molecular Markers in Immunotherapy and Targeted Therapy of Colorectal Cancer in Tibet

Objective To study the expression of SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4(SMARCA4)/Brahma-related gene 1,V-raf murine sarcoma viral oncogene homolog B(BRAF),P53,programmed cell death protein-1(PD-1),and programmed death-ligand 1(PD-L1),and changes in the expression of BRAF and neurotrophic tyrosine receptor kinase(NTRK) in the patients with colorectal cancer in Tibet,thereby providing a basis for targeted therapy and immunotherapy for this disease in Tibet. Methods A total of 64 patients with colorectal cancer resected in the Tibet Autonomous Region People's Hospital from January 2015 to July 2021 were enrolled in this study.The expression of SMARCA4,BRAF,P53,PD-1,and PD-L1 was detected by immunohistochemical staining.The gene fusion involving NTRK1,NTRK2,and NTRK3 was detected by fluorescence in situ hybridization,and the BRAF V600E gene mutation by polymerase chain reaction. Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of (56.59±13.27) years.The tumors were located in the colon in 46(71.88%) patients and in the rectum in 18(28.12%) patients.Sixty(93.75%) patients presented adenocarcinoma,and 4(6.25%) patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n=11) and 82.81%(n=53),respectively.Lymph node metastasis occurred in 24(37.50%) patients.The immunohistochemical staining results showed partially down-regulated or absent expression of SMARCA4 in 1(1.56%) patient,positive BRAF expression in 4(6.25%) patients,and mutant expression of P53 in 35(54.69%) patients.The PD-1-expressing tumor associated immune cell was proportion score<10% in 45(70.31%) patients and≥10% in 19(29.69%) patients.The PD-L1 combined positive score was<10 in 52(81.25%) patients and≥10 in 12(18.75%) patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%) patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/microsatellite instability-high (MSI-H) and the PD-1 expression (χ2=10.223,P=0.001;χ2=11.979,P=0.001). Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunotherapy.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.

Relationship between chronic disease resource utilization and quality of life in coronary heart disease patients: A latent profile analysis.

This study aimed to identify different profiles of chronic disease resource utilization among patients with coronary heart disease in Tibet and explore the relationship between these profiles and quality of life. A cross-sectional study. Patients with coronary heart disease who were treated in a tertiary hospital in Tibet and its cooperative points from January 2021 to July 2021 were selected as the study participants. All participants completed a general information questionnaire, the Chronic Disease Resource Utilization Questionnaire (CIRS) and the Health Status Survey Short Form (SF-36). Chronic disease resource utilization was profiled, and its relationship to quality of life was explored using hierarchical linear regression. A total of 382 patients were enrolled in this study. Regarding chronic disease resource utilization, the participants were divided into three latent profiles: 'Poor utilization group' (n = 151), 'Effective utilization group' (n = 155) and 'Full utilization group' (n = 76). Different profiles of chronic disease resource utilization of patients were significantly associated with quality of life (R2 = .126, p < .001). Healthcare providers should identify patients with different profiles, define their utilization features of chronic disease resources and adopt targeted interventions to guide them in acquiring enough disease support resources to improve their quality of life. Understanding different resources using preferences of coronary heart disease patients can help healthcare providers and related sectors to provide other supports based on different profiles of patients, thus enhancing their quality of life. The study followed the STROBE guideline. There was no patient or public involvement in the design of the study.

Factors influencing the spatial distribution and individual variation in urinary fluoride levels in Tibet, China

Nowadays, fluorosis is the most prevalent endemic disease in Tibet and one of the most concerned public health problems in China; urinary fluoride is a common diagnostic indicator of endemic fluorosis. However, the spatial distribution and influencing factors of urinary fluoride content in Tibet remain unclear. This study aims to bridge this gap by geographically weighted regression (GWR), analyses of variance (ANOVAs), Geodetector, and stepwise multiple linear regression (MLR). To achieve this goal, this study first investigated fluoride levels in the fasting urine among 637 Tibetan residents from 73 counties in Tibet, the urinary fluoride level was chosen as an indicator of fluorosis, which can reflect the health impairment. Then we identified the potential factors that could influence the spatial distribution and individual variation of urinary fluoride levels from physical environmental and socioeconomic perspective, respectively. The results showed that urinary fluoride levels in Tibet were slightly exceeding the average value for adult urinary fluoride in China, and that residents with high urinary fluoride were mainly found in the west and east; those with low urinary fluoride were mainly found in the central-southern regions. And the urinary fluoride levels had a significantly positive correlation with water fluoride and a significantly negative correlation with average annual temperature. Urinary fluoride levels increased until age 60 and followed an inverted “U”-shaped trajectory according to annual household income (80,000 renminbi (RMB) was the inflection point); pastoralists had greater exposure to fluoride than farmers. Furthermore, the Geodetector and MLR showed that the urinary fluoride level was influenced by both physical environmental and socioeconomic factors. The socioeconomic factors such as age, annual household income and occupation had a greater impact than the physical environment on urinary fluoride concentration. These findings can provide scientific basis for preventing and controlling endemic fluorosis in the Tibetan Plateau and adjacent areas.

Morphological and Molecular Identification of Peach Brown Rot Disease in Tibet and Exploration of the Biocontrol Efficiency of Trichoderma.

Brown rot caused by the pathogen of the genus Monilinia is the most destructive disease in peaches worldwide. It has seriously reduced the economic value of the peach (Prunus persica (L.) Batsch) in Nyingchi and Qamdo, Tibet, China. Monilinia fructicola, Monilia mumecola, and M. yunnanensis have been reported as the causal agents of brown rot disease on stone fruits in China. In this study, we report on the identification of M. yunnanensis in peach orchards in Nyingchi and Qamdo, Tibet. From twenty-three isolates with the same characteristics, we identified the representative single-spore isolates T8-1, T8-8, and T8-20 as M. yunnanensis and confirmed that the Tibet brown rot disease was caused by M. yunnanensis based on the morphological characteristics and molecular analyses. The phylogenetic analysis of the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) and β-tubulin (TUB2) nucleotide sequences and the multiplex PCR identification revealed that the representative isolates T8-1, T8-8, and T8-20 were more closely related to M. yunnanensis than other Monilinia species. Furthermore, the biocontrol strain of Trichoderma T6 presented significant antagonistic activity on the M. yunnanensis T8-1 isolate (T8-1) among the five Trichoderma strains. The highest inhibitory rates for Trichoderma T6 and its fermentation product against T8-1 mycelial growth were 72.13% and 68.25%, respectively. The obvious inhibition zone displayed on the colony interaction area between the colony of T8-1 isolate and Trichoderma T6 and the morphological characterization of the T8-1 hyphae were enlarged and malformed after inoculation with the Trichoderma T6 fermentation product at 20-fold dilution. Our results indicate that the strain of Trichoderma T6 could be considered as a beneficial biocontrol agent in managing brown rot of peach fruit disease.

Health literacy and quality of life of patients with coronary heart disease in Tibet, China: The mediating role of self-efficacy and self-management

BackgroundThe disease burden of coronary heart disease patients in Tibet, China, ranks high in the country. Due to the local culture and environment, patients with coronary heart disease have increased risk factors for the disease, and their survival is worrisome. ObjectivesThe purpose of this study was to determine the relationship between health literacy and quality of life for patients with coronary heart disease in Tibet, China, and to explore the mediating roles of self-efficacy and self-management. MethodsA cross-sectional study was conducted from August 2020 to July 2021 in Tibet. A total of 258 patients with coronary heart disease in Tibet participated. Self-reported questionnaires were used to assess health literacy, self-efficacy, self-management, and quality of life. Pearson correlation analysis and the SPSS PROCESS macro were used to analyze the data. ResultsThe mean total score for the health literacy of patients with coronary heart disease in Tibet was 3.59 ± 0.80 points, showing the existence of a limited level of literacy. The quality of life was of an average level, with scores of 57.20 ± 21.70 points and 63.63 ± 20.66 points for physical and mental status, respectively. Self-efficacy and self-management mediated the relationship between health literacy and quality of life. ConclusionsSelf-efficacy and self-management mediate the relationship between health literacy and quality of life. Targeted interventions for health literacy, self-efficacy, and self-management skills are important to improve the quality of life of Tibetan patients with coronary heart disease.

Prevalence of pediatric Kashin-Beck disease in Tibet.

To estimate the prevalence of Kashin-Beck disease (KBD) among children in 2017 in Changdu of Tibet. We adopted a four-step recruitment to include children aged 7-12 years from seven identified historically endemic counties in Changdu. Posterior-anterior radiographs of right hand and wrist were taken and were graded at four sites (metaphysis, epiphysis, and bony end of phalanges and metacarpal and carpal bones). Two trained researchers independently read the films. Inter-rater reliability was assessed using weighted Kappa and percentage agreement. We fitted logistic regression model to examine the association of age, sex, and altitude of residential village with prevalence of KBD. We examined association between site involvement and severity of KBD using chi-square test. We recruited 13,573 children (mean age = 9.3 years, 48.40% girls) with a response rate of 95.81%. The overall prevalence of radiographic KBD was 0.26%. Luolong County had the highest prevalence (0.69%), followed by Bianba (0.26%), Basu (0.24%), Mangkang (0.14%), Zuogong (0.14%), Dingqing (0.07%), and Chaya (0.00%). A higher risk of radiographic KBD was associated with older age (P for trend <0.001) and girls (OR=1.86, 95% CI: 0.94, 3.70), but not the altitude of residential village (P for trend=0.957). Metaphysis was involved in all cases of KBD while lesions in epiphysis and bony end of phalanges and metacarpals were only observed in severe cases. The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu compared with previous census data, suggesting the effectiveness of preventative measures. Key Points • In this study, 13,573 Tibetan children were taken X-ray films of their hands and wrists. • The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu of Tibet. • The preventative measures against KBD launched by Chinese government were effective in decreasing new onsets of KBD among Tibetan children.

A case of Caroli disease in Tibet, China

A case of Caroli disease in Tibet, China

Hypolipidemic and Antioxidant Effects of Malus toringoides (Rehd.) Hughes Leaves in High-Fat-Diet-Induced Hyperlipidemic Rats.

Malus toringoides (Rehd.) Hughes (MT) leaves are traditionally used as a medicine for treating or preventing cardiovascular disease in Tibet. In addition to the effect of this medicinal plant on thrombosis, we tested its effect on dyslipidemia in a hypolipidemic rat model. A total of 60 healthy Sprague-Dawley rats were randomly divided into six groups, as follows: normal control, model control, simvastatin groups, and MT low-, medium-, and high-dose groups. The normal controls were fed with a normal diet, whereas all other groups were fed with a high-fat diet. After 6 weeks, the high-fat diet had induced hyperlipidemia in the rats, which were then orally administered with different doses of MT leaf extract (50, 100, and 200 mg/kg) for an additional 6 weeks. Serum levels of total cholesterol (TC), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-c and HDL-c, respectively), as well as the antioxidant capacity of glutathione peroxidase (GSHP-x), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured at the end of the study. MT significantly reduced serum TC, TG, and LDL-c and increased the HDL-c content in MT-treated rats compared with the model group. These changes were dose dependent. MT treatment also significantly elevated the activity of SOD and GSHP-x, and decreased the serum levels of MDA compared with untreated hyperlipidemic rats, thereby increasing serum antioxidant capacity. In addition, MT reduced liver steatosis in hyperlipidemic rats. Overall, MT exerts considerable hypolipidemic and antioxidant properties.

Radiological Abnormalities and Clinical Characteristics for Children with Kashin-Beck Disease in Tibet

A radiological study and clinical characteristics in Kashin-Beck Disease (KBD) was undertaken on the appendicular skeleton in 213 patients with KBD in Tibet , in 134 healthy subjects living in an endemic area and in 61 healthy subjects living in a non-endemic area. Eight clinical symptoms and radiological signs of different joints in patients with Kashin-Beck disease (KBD) were studied in all cases. Arthritic pain in ankles and knee joints was the most common symptom in the early and advanced KBD children groups (1.6%,18.9%) and was significantly higher than in the in the other groups (P&lt;0.05). Morning stiffness was observed in the all groups. Abnormal radiological changes of the finger phalanges were present in a high percentage of patients (72.9%, 86.7%) in the KBD group but that this did not occur in the healthy group. It is suggested that finger phalanges of X-rays and some clinical symptoms might be a specific criterion for diagnosing KBD.

Effects of physical environment on the evolution of Kashin-Beck disease in Tibet

In previous studies we observed a proximo-distal gradient of lesion frequencies along the limb, with the distal joints being the most often affected. This suggests an associated effect of environmental factors on the most exposed joints. On a population of 820 children (mean age 13 years) of endemic areas distributed in groups of healthy and severity stages I to III of KBD (Kashin-Beck disease), the effects of different working activities were studied. Heavy work like that of a ploughman were compared to light physical work, e.g. school children, and exposure to cold and history of frostbite were also considered. The most severe stages, II and III, were present in 72% of the ploughman vs. 29% of the schoolchildren, 70% of the shepherds vs. 30% (p < 0.001) of the schoolchildren, and in 65% of the shepherds working in winter vs. 40% of those working in the other seasons (p < 0.001). In the group with history of frostbite, 58% present the severest stages vs. 40% without (p < 0.001). The results confirm a highly significant relation between microtrauma and cold and the severity of the KBD alterations.

Relationship between selenium concentration in child hair and the distribution of Kashin-Beck disease in Tibet, China

The focus of this study is to determine the relationship between selenium (Se) concentrations in child hair and the distribution of Kashin-Beck disease (KBD) in Tibet. The hair of children in typical KBD-affected areas and non-disease areas was collected, and its Se concentrations were measured by atomic fluorescent spectrometry. The Se concentrations in child hair were (0.13±0.04) and (0.18±0.07) μg/g respectively in KBD areas and non-disease areas respectively, which are significantly different. In areas supplemented with Se in Tibet, the Se concentration of hair in KBD-affected areas was higher than that in non-diseased areas, being (0.28±0.03) and (0.18±0.04) μg/g respectively. There is a close relationship between the Se concentrations in hair and KBD distribution. Se supplement increase the Se concentrations in the human body. Appropriate Se supplementation is important to prevent KBD in Tibet.

The anatomical distribution of radiological abnormalities in Kashin-Beck disease in Tibet.

A radiological study of osteoarticular changes in Kashin-Beck Disease (KBD) was undertaken on the appendicular skeleton in 105 patients with KBD, in 31 healthy subjects living in an endemic area and in 30 healthy subjects living in a non-endemic area. The bone age was delayed in all three populations with no significant difference between the three studied Tibetan populations. Radiological changes occur in 56% of patients with KBD, and are usually bilateral. An analysis of the distribution of lesions shows a proximo-distal gradient. The changes are more common in the distal aspect of the limb and the lower limb is involved more commonly than the upper limb. The foot and ankle are involved in 89.5% of cases. The radiological changes and their distribution might be explained by the hypothesis of inhibition of angiogenesis by mycotoxins, exacerbated by chemical and physical environmental factors.

Epidemiological support for a multifactorial aetiology of Kashin-Beck disease in Tibet.

We carried out a cross-sectional study in 12 rural villages in order to identify the risk factors for Kashin-Beck disease in Tibet. Children aged 5-15 years (n=575) were examined and their corresponding houses were visited. Samples were collected in order to study fungal contamination of stored grain and the organic matter content of drinking water. Multivariate analysis was performed using logistic regression and population attributable fractions were computed to estimate the impact of each factor. The following variables were independently associated with the disease: age, gender, low socio-economic status, indicators of a poorly diversified diet, iodine deficiency and small water container size (with higher organic matter levels in small containers). Selenium deficiency was severe in all study subjects. The degree of fungal contamination of barley grain was related to the highest percentage of cases (65%) in a sample of the study population. Higher urinary iodine levels were not associated with decreasing prevalence rates when Alternaria sp. was isolated. The data that we report supports the hypothesis that Kashin-Beck disease occurs as a consequence of oxidative damage to cartilage and bone cells when associated with decreased antioxidant defence. Another mechanism that may coexist is bone remodelling stimulated by thyroid hormones whose actions can be blocked by certain mycotoxins.

A 4-year study of the mycological aspects of Kashin-Beck disease in Tibet.

In order to clarify the association between mycotoxin-producing fungi in food and Kashin-Beck disease (KBD), we examined the occurrence and contamination levels of fungi in samples of barley grain, from KBD-affected families and from unaffected families in endemic areas. A control area without the occurrence of KBD served as reference. The first results obtained in 1995 showed that total mesophilic fungal contamination of barley grain was consistently higher in families with KBD. Trichothecium roseum (Pers) Link ex gray, Dreschlera Ito and Alternaria Nees ex Fr. were the three most common fungi significantly associated with KBD. In 1996 we again observed a significant difference between affected and non-affected families, especially with Trichothecium roseum and Ulocladium Preuss. On this basis, measures to prevent KBD were suggested and a preventive program has been set up since 1998 in 20 new villages.

Fungal contamination in barley and Kashin-Beck disease in Tibet

5First results showed that mesophilic fungal contaminations were significantly higher on barley grains stored in families with KBD (median 66% of grains infected) than in healthy families (median 43% of grains infected) (Kruskal-Wallis p<0·01). The risk of KBD associated with the presence of fungal taxa on barley grains was expressed in odds ratios (ORs), adjusted for age and sex and calculated with logistic regression. Three common fungal taxa in grains were significantly associated with KBD. Trichothecium roseum (Pers) Link ex Gray (OR16·37, p<0·001), Dreschlera Ito (OR8·75, p<0·001) and Alternaria Nees ex Fr (OR2·96, p<0·001). ORs adjusted for the presence of other fungi concerned showed an independent effect of each of these three taxa. However the effect of Dreschlera was significantly higher in presence of a fourth taxon. Cladosporium Link ex Fr, indicating an interaction (p<0·05). Compared with the absence of fungi, the cumulative effect of different fungal associations can be estimated (figure). On the basis of these results, we conclude that, in Tibet, there are two critical periods for fungal grain contamination related to KBD. First, during the growing season, from contaminated seeds (Dreschlera) or from contaminated debris of the preceding harvest (Alternaria, Cladosporium). Second, just after harvest, during the drying period in the field, especially when the daily difference of temperature is high (dewy grains) and consequently, at the beginning of the storage, when too moist grains are placed in bags or other containers (Trichothecium roseum and also Alternaria and Cladosporium). As measures to prevent KBD in Tibet, we suggest disinfection of barley seeds, destruction of crop residues, and efficient grain drying before storage.

Preliminary research on forest diseases of Tibet

The general situation of forest and forest disease in Tibet is presented. Based on the author’s field work in Tibetan forests and the identification of forest disease, specimens which were collected is 2 species of parasitic plants and 26 species of fungal pathogens. Among fungal pathogens 13 species were not reported in “Fungi of Tibet”. The author analyses the situation and characteristics of forest diseases in Tibet and presents an exploratory suggestion that an “Ecological Research Station for Forest Diseases” should be established in Tibet. The objective would be to establish a healthy “forest ecosystem” where human are in harmony with nature.