Calcium-sensing stromal interaction molecule 2 upregulates nuclear factor of activated T cells 1 and transforming growth factor-ß signaling to promote breast cancer metastasis.

BACKGROUND: Stromal interaction molecule (STIM) 2 is a key calcium-sensing molecule that regulates the stabilization of calcium ions (Ca2+) and therefore regulates downstream Ca2+-associated signaling and cellular events. We hypothesized that STIM2 regulates epithelial-mesenchymal transition (EMT) to promote breast cancer metastasis. METHODS: We determined the effects of gain, loss, and rescue of STIM2 on cellular motility, levels of EMT-related proteins, and secretion of transforming growth factor-ß (TGF-ß). We also conducted bioinformatics analyses and in vivo assessments of breast cancer growth and metastasis using xenograft models. RESULTS: We found a significant association between STIM2 overexpression and metastatic breast cancer. STIM2 overexpression activated the nuclear factor of activated T cells 1 (NFAT1) and TGF-ß signaling. Knockdown of STIM2 inhibited the motility of breast cancer cells by inhibiting EMT via specific suppression of NFAT1 and inhibited mammary tumor metastasis in mice. In contrast, STIM2 overexpression promoted metastasis. These findings were validated in human tissue arrays of 340 breast cancer samples for STIM2. CONCLUSION: Taken together, our results demonstrated that STIM2 specifically regulates NFAT1, which in turn regulates the expression and secretion of TGF-ß1 to promote EMT in vitro and in vivo, leading to metastasis of breast cancer.

STIM1 and STIM2 differently regulate endogenous Ca2+ entry and promote TGF-ß-induced EMT in breast cancer cells.

The Ca2+ sensor proteins STIM1 and STIM2 are crucial elements of store-operated calcium entry (SOCE) in breast cancer cells. Increased SOCE activity may contribute to epithelial-mesenchymal transitions (EMT) and increase cell migration and invasion. However, the roles of STIM1 and STIM2 in TGF-ß-induced EMT are still unclear. In this study, we demonstrate roles of STIMs in TGF-ß-induced EMT in breast cancer cells. In particular, STIM1 and STIM2 expression affected TGF-ß-induced EMT by mediating SOCE in MDA-MB-231 and MCF-7 breast cancer cells. The specific SOCE inhibitor YM58483 blocked TGF-ß-induced EMT, and differing effects of STIM1 and STIM2 on TGF-ß-induced EMT correlated with differing roles in SOCE. Finally, we showed that STIM2 is associated with non-store-operated calcium entry (non-SOCE) during TGF-ß-induced EMT, whereas STIM1 is not. What's more, non-SOCE have a large possibility to be ROCE. In conclusion, STIM1 and STIM2 proteins play important roles in TGF-ß-induced EMT and these effects are related to both SOCE and non-SOCE.

Medical Discrimination Affects the HIV/AIDS Epidemic Control: A Study of Self-Perceived Medical Discrimination on People Living with HIV or AIDS.

People living with HIV or AIDS (PLWHA) experienced severe medical discrimination which is seriously affecting their lives. However, few studies examined the epidemic characteristics of self-perceived medical discrimination from the discrimination objects such as PLWHA. Therefore, we aimed to investigate the epidemiological status and analyze the influential factors of the self-perceived medical discrimination on PLWHA in South China. The self-designed questionnaire was used to investigate the medical discrimination status of the 443 infected persons, who were randomly recruited from the representative AIDS designated hospitals in Guangdong Province in South China. The results showed that 49.0% of PLWHA experienced medical discrimination, and 55.3% received discriminatory treatment, 48.4% experienced refusal of treatment, 36.4% had private information leaked and 12.9% received mandatory test. However, 52.2% patients chose to endure discrimination in silence. Compared with the Asymptomatic HIV-infected patients, AIDS patients perceived more medical discrimination. The Logistic regression analysis indicated that PLWHA self-perceived medical discrimination status was influenced by 4 factors: the voluntary of first medical detection, the route of transmission, the stage of the disease and the familiarity with the HIV/AIDS-related law. Additionally, the two dimensions of the life quality scale were influenced by medical discrimination, namely, overall function and disclosure worry. Ultimately, our study provides a better understanding of the relationship between infection status, quality of life and the medical discrimination they experienced or perceived. It will help health professionals and policy makers to develop tailored behavioral and policy-oriented intervention strategies for PLWHA to tackle different types of medical discrimination in high-risk settings.

Focusing on exosomes to overcome the existing bottlenecks of CAR-T cell therapy.

Since chimeric antigen receptor T (CAR-T) cells were introduced three decades ago, the treatment using these cells has led to outstanding outcomes, and at the moment, CAR-T cell therapy is a well-established mainstay for treating CD19 + malignancies and multiple myeloma. Despite the astonishing results of CAR-T cell therapy in B-cell-derived malignancies, several bottlenecks must be overcome to promote its safety and efficacy and broaden its applicability. These bottlenecks include cumbersome production process, safety concerns of viral vectors, poor efficacy in treating solid tumors, life-threatening side effects, and dysfunctionality of infused CAR-T cells over time. Exosomes are nano-sized vesicles that are secreted by all living cells and play an essential role in cellular crosstalk by bridging between cells. In this review, we discuss how the existing bottlenecks of CAR-T cell therapy can be overcome by focusing on exosomes. First, we delve into the effect of tumor-derived exosomes on the CAR-T cell function and discuss how inhibiting their secretion can enhance the efficacy of CAR-T cell therapy. Afterward, the application of exosomes to the manufacturing of CAR-T cells in a non-viral approach is discussed. We also review the latest advancements in ex vivo activation and cultivation of CAR-T cells using exosomes, as well as the potential of engineered exosomes to in vivo induction or boost the in vivo proliferation of CAR-T cells. Finally, we discuss how CAR-engineered exosomes can be used as a versatile tool for the direct killing of tumor cells or delivering intended therapeutic payloads in a targeted manner.

Ultrasound-assisted extraction of polyphenols from pine needles (Pinus elliottii): Comprehensive insights from RSM optimization, antioxidant activity, UHPLC-Q-Exactive Orbitrap MS/MS analysis and kinetic model.

Extracting polyphenolic bioactive compounds from Pinus elliottii needles, a forestry residue, promises economic and environmental benefits, however, relevant experimental data are lacking. Herein, a comprehensive investigation of the polyphenolic composition of pine needles (PNs) was carried out. Ultrasound-Assisted Extraction (UAE) was applied to extract the polyphenolic compounds of pine needles. The optimal conditions of extracts were determined by Response Surface Methodology (RSM). The maximum total phenolic content (TPC) of 40.37 mg GAE/g PNs was achieved with solid-liquid ratio of 1:20, 60 % ethanol, and 350 W for 25 min at 45 °C. Polyphenolic extracts showed antioxidant activity in scavenging free radicals and reducing power (DPPH, IC50 41.05 µg/mL; FRAP 1.09 mM Fe2+/g PNs; ABTS, IC50 214.07 µg/mL). Furthermore, the second-order kinetic model was also constructed to describe the mechanism of the UAE process, with the extraction activation energy estimated at 12.26 kJ/mol. In addition, 37 compounds in PNs were first identified by UHPLC-Q-Exactive Orbitrap MS/MS, including flavonoids and phenolic acids. The results suggest that Ultrasound-Assisted is an effective method for the extraction of natural polyphenolic compounds from pine needles and this study could serve as a foundation for utilizing phenolics derived from PNs in the food and pharmaceutical industries.

Prognostic value of neutrophil to lymphocyte ratio in gastric cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: The neutrophil to lymphocyte ratio (NLR) is a cost-effective and easily identifiable inflammatory biomarker that has been shown to be closely associated with tumor prognosis and predict survival in patients with multiple malignancies. However, the predictive value of NLR in patients with gastric cancer (GC) treated with immune checkpoint inhibitors (ICIs) has not been fully explored. Therefore, we conducted a meta-analysis to explore the potential of NLR as a predictor of survival in this population. Methods: We systematically searched the PubMed, Cochrane Library, and EMBASE databases from inception to the present for observational researches on NLR and its relationship with progression or survival in GC patients receiving ICIs. To assess the prognostic significance of NLR on overall survival (OS) or progression-free survival (PFS), we used fixed or random-effect models to derive and combine hazard ratios (HRs) with 95% confidence intervals (CIs). We also examined the relationship between NLR and treatment efficacy by calculating relative risks (RRs) with 95% CIs for objective response rate (ORR) and disease control rate (DCR) in patients with GC receiving ICIs. Results: Nine studies of 806 patients were eligible. OS and PFS data were obtained from 9 and 5 studies, respectively. In nine studies, NLR was associated with poor survival, the pooled HR was 1.98 (95% CI 1.67- 2.35, p < 0.001), indicating a significant association between high NLR and worse OS. We conducted subgroup analyses based on study characteristics to confirm the robustness of our findings. A relationship between NLR and PFS were reported in five studies with a HR of 1.49 (95% CI 0.99- 2.23, p = 0.056), which was not significantly associated. Pooling four studies that examined the correlation between NLR and ORR/DCR in GC patients, we observed a significant correlation between NLR and ORR (RR = 0.51, p = 0.003), but no significant correlation between NLR and DCR (RR = 0.48, p = 0.111). Conclusion: In summary, this meta-analysis indicates that increased NLR is significantly linked to worse OS in patients with GC receiving ICIs. In addition, lowering NLR can improve ORR. Thus, NLR can serve as a predictor for prognosis and treatment response in GC patients treated with ICIs. Nevertheless, further high-quality prospective studies are required to verify our findings in the future.

MGA-seq: robust identification of extrachromosomal DNA and genetic variants using multiple genetic abnormality sequencing.

Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA's transcriptional regulatory function.

Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation.

Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose "degree of disorder" to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.

Delineating the organization of projection neuron subsets in primary visual cortex with multiple fluorescent rabies virus tracing.

The impressive functions of the brain rely on an extensive connectivity matrix between specific neurons, the architecture of which is frequently characterized by one brain nucleus/region connecting to multiple targets, either via collaterals of the same projection neuron or several, differentially specified neurons. Delineating the fine architecture of projection neuron subsets in a specific brain region could greatly facilitate its circuit, computational, and functional resolution. Here, we developed multiple fluorescent rabies viruses (RV) to delineate the fine organization of corticothalamic projection neuron subsets in the primary visual cortex (V1). By simultaneously retrograde labeling multiple distinct subsets of corticothalamic projection neurons in V1 from their target nuclei in thalamus (dLGN, LP, LD), we observed that V1-dLGN corticothalamic projection neurons were densely concentrated in layer VI, except for several sparsely scattered neurons in layer V, while V1-LP and V1-LD corticothalamic projection neurons were localized to both layers V and VI. Meanwhile, we observed a fraction of V1 corticothalamic projection neurons targeting two thalamic nuclei, which was further confirmed by fMOST whole-brain imaging. The multiple fluorescent RV tracing tools can be extensively applied to resolve the architecture of projection neuron subsets in certain brain regions, with a strong potential to delineate the computational and functional organization of these brain regions.

Digestion-ligation-only Hi-C is an efficient and cost-effective method for chromosome conformation capture.

Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments. Notably, random ligation could be quickly evaluated in an early quality-control step before sequencing. Moreover, an in situ version of DLO Hi-C using a four-cutter restriction enzyme has been developed. We applied DLO Hi-C to delineate the genomic architecture of THP-1 and K562 cells and uncovered chromosomal translocations. This technology may facilitate investigation of genomic organization, gene regulation, and (meta)genome assembly.

Analysis of National Major Work Safety Accidents in China, 2003-2012.

BACKGROUND: This study provides a national profile of major work safety accidents in China, which cause more than 10 fatalities per accident, intended to provide scientific basis for prevention measures and strategies to reduce major work safety accidents and deaths. METHODS: Data from 2003-2012 Census of major work safety accidents were collected from State Administration of Work Safety System (SAWS). Published literature and statistical yearbook were also included to implement information. We analyzed the frequency of accidents and deaths, trend, geographic distribution and injury types. Additionally, we discussed the severity and urgency of emergency rescue by types of accidents. RESULTS: A total of 877 major work safety accidents were reported, resulting in 16,795 deaths and 9,183 injuries. The numbers of accidents and deaths, mortality rate and incidence of major accidents have declined in recent years. The mortality rate and incidence was 0.71 and 1.20 per 10(6) populations in 2012, respectively. Transportation and mining contributed to the highest number of major accidents and deaths. Major aviation and railway accidents caused more casualties per incident, while collapse, machinery, electrical shock accidents and tailing dam accidents were the most severe situation that resulted in bigger proportion of death. CONCLUSION: Ten years' major work safety accident data indicate that the frequency of accidents and number of eaths was declined and several safety concerns persist in some segments.

[Analysis on the individual-response behavior and the influence factors to violent terrorist attacks among undergraduates in Guangzhou].

OBJECTIVE: To analyze related behaviors of individual preparedness and influencing factors on violent terrorist attacks among undergraduates. METHODS: A total of 1 800 undergraduates from 5 colleges or universities in Guangzhou were selected, using the stratified cluster method. A questionnaire involving the response to violent terrorist attack behavior was used to assess the individual preparedness behaviors among undergraduates. A self-made questionnaire was applied to collect information on demographic factors, cognitive and preparedness behaviors. RESULTS: The mean score of individual preparedness behavior among undergraduates was 13.49 ± 5.02 while information on seeking behavior was 4.27 ± 1.64, avoidance behavior was 5.97 ± 2.16 and violent terrorist attack response behaviors was 23.73 ± 7.21, with 30.0 percent of undergraduates behaved properly. Significant differences were found in the scores of behaviors on the response to violent terrorist attack with different gender, major they pursue or religious belief (P < 0.05), among undergraduates involved in this study. Results from the logistic regression analysis revealed that persons being girls (OR = 1.46, 95% CI: 1.06-2.01), with bigger perceived probability (OR = 1.60, 95% CI: 1.12-2.30), with higher alertness (OR = 3.77, 95% CI: 2.15-6.61), with stronger coping confidence (OR = 0.34, 95% CI: 0.24-0.48) and bigger affective response (OR1 = 3.42, 95% CI: 2.40-4.86; OR2 = 0.23, 95% CI: 0.13-0.41), would present more prominent behavior responses when facing the violent terrorist attack. CONCLUSION: Individual response behaviors to violent terrorist attacks among undergraduates were relatively ideal. Perceived probability, alertness, coping confidence and affective response appeared to be independent influencing factors related to response behaviors against violent terrorist attack. In colleges and universities, awareness on violent terrorist attacks should be strengthened among undergraduates. Focus should target on psychological education dealing with disaster, knowledge and skills needed for emergency response, so as to respond to the emergency on campus.

Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice.

Phenytoin (PHT) is a commonly prescribed first-line antiepileptic drug. However, long-term administration of PHT can cause memory loss and balance disturbance. Gastrodin (GD) is the major bioactive component in Tianma and has sedative, anticonvulsive, memory strengthening, and neuroprotective effects. To combine the two drugs seems attractive; however, little was known about the efficacy of combination therapy. In this study, convulsive attack was successfully induced by penicillin. Isobolographic analysis, memory and balance behavior test, histopathological examination, and Western blot analysis were used to investigate whether the combination therapy of GD and PHT can enhance anticonvulsive effect and reduce the side effects associated with PHT. The GD alone (950.60 mg/kg) and the PHT alone (45.50 mg/kg) could produce an anticonvulsive effect, while comparable effect could be produced by PHT : GD = 1 : 50 (8.59 : 429.27 mg/kg), which reduce the dose of PHT by 81% and GD by 55%. After the chronic anticonvulsive experiments of 16 days, the balance disturbance and short-/long-term memory loss were observed in the PHT group, while the PHT + GD therapy can protect the normal balance and memory function. The neuron morphology of hippocampus was preserved, and the number of surviving neurons after combination therapy was more than the model group. The amount of NF-κB (p65) expression was increased in combination group. All above suggested the potential of the combination of PHT and GD enhances the anticonvulsive effect and the neuroprotective effect and reduces the PHT-associated memory and balance disturbance. The PHT + GD strategy would provide new possibilities as a novel promising methodology to treat epileptic patients.

[Quality of life and related factors among people living with HIV/AIDS in Guangdong province].

OBJECTIVE: To explore the quality of life and related factors among people living with HIV/AIDS in Guangdong province. METHODS: A total of 443 subjects older than age 18 who had been diagnosed as HIV/AIDS were recruited from AIDS Outpatient Clinic Departments in Guangzhou and Shenzhen. HIV/AIDS-targeted quality of life(HAT-QoL)scale was used to measure the quality of life on the patients. Nonparametric test method and multiple linear regression analysis were performed to explore the related factors. RESULTS: The average scores of the following nine domains of HIV/AIDS-targeted quality of life scales were:overall function as 59.89 ± 23.35, concerns on medication as 62.91 ± 24.01, worries on factors as being disclosed, on health, on financial situation were 19.97 ± 23.04, 54.05 ± 12.24 and 35.94 ± 26.45, respectively, trust on providers as 68.72 ± 26.17, rate of understanding HIV as 61.46 ± 25.72, on life satisfaction as 56.90 ± 25.30 and on sexual function as 50.82 ± 23.86. Factors associated with quality of life would include sex, age, residential area, education, employment, marital status, complications, HAART-related prescriptions, route of infection and duration of HIV/AIDS etc. CONCLUSION: The quality of life among HIV/AIDS patients had declined, especially on worries related to disclosure and financial situation. More attention should be paid on those with poor education, low income and lack of family support in order to improve their quality of life and reducing mortality.

The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis.

Although the polymorphisms of PTPN22 and the variants of CTLA-4 have been reported to be the susceptibility genes, which increased risk of latent autoimmune diabetes in adults (LADA), the results remained inconclusive. The aim of this meta-analysis was to evaluate the association between the polymorphisms of two genes and LADA. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. Data from ten studies published between 2001 and 2013 were pooled for two polymorphisms: rs2476601 in the PTPN22 gene and rs231775 in the CTLA-4 gene. Data extraction and assessments for risk of bias were independently performed by two reviewers. Fixed-effect model and random-effect model were used to pool the odds ratios; meanwhile, heterogeneity test, publication bias and sensitive analysis were explored. The minor T allele at rs2476601 and the minor G at rs231775 carried estimated relative risks (odds ratio) of 1.52 (95 % CI 1.29-1.79) and 1.39 (95 % CI 1.11-1.74), respectively. These alleles contributed to an absolute lowering of the risk of all LADA by 4.88 and 14.93 % when individuals do not carry these alleles. The estimated lambdas were 0.49 and 0.63, suggesting a codominant model of effects was most likely for two genes. In summary, our systematic review has demonstrated that PTPN22 rs2476601 and CTLA-4 rs231775 are potential risk factors for LADA. An updated meta-analysis is required when more studies are published to increase the power of these polymorphisms and LADA.

[Meta-analysis on the incidence rates of child sexual abuse in China].

OBJECTIVE: To offer basic data related to the prevention of child sexual abuse, we conducted a Meta-analysis on the national incidence rate on child sexual abuse in the country. METHODS: Publications between 2000 and 2013 were extracted from PubMed, Springer Link, Elsevier-SDOL, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science & Technology journal database (VIP), Wanfang Databases, China master's Theses Full-text Database and China Conference Papers Full-text Database. Observational studies which containing the incidence rate of child sexual abuse were included. We used the Loney criteria to evaluate the quality of searched publications. The Meta incidence rate was estimated using the Stata software. Subgroup analysis were undertaken on gender issues. Sensitivity analysis were performed to evaluate the impact of types or qualities to the research objects. RESULTS: Fifteen papers were included in this Meta-analysis, with a sample size of 16 682. The combined incidence rate of child sexual abuse was 18.20% (95%CI:13.74%-22.66%). For injured persons, girls had a higher incidence rate on child sexual abuse (11.22%) than boys (8.25%) in terms of contact sexual abuse, but no significant difference on gender was found in the prevalence rates of global and un-contact sexual abuse. Data from sensitivity analysis revealed that the quality or types of the objects slightly affected the incidence rate of traffic injuries. CONCLUSION: of this study indicated that child sexual abuse was common and serious in China, suggesting that prevention and control programs on childhood abuse should be emphasized and promoted.

[Consciousness and abilities on health emergency and the roles of emergency response among public at the communities].

OBJECTIVE: To evaluate the consciousness of health emergency and the abilities on self- and mutual medical aids among the public at the community level, as well as the community responses on health-related emergencies and other factors. METHODS: Random equidistant sampling method was used to extract 617 households before choosing a family member sampled by Kish Grid method. All the members were investigated face to face on a questionnaire-"Health emergency and related ability regarding self and mutual medical aids of the residents". Data were entered into computer database by using software Epi Data 3.1 and were analyzed by SPSS 21.0. RESULTS: Among the 617 households under survey, 47.84% of the public had general awareness on health-related emergencies. Regarding the following items as:prevention and isolation strategies of infectious disease, on safely procedures of earthquake and fires, on prevention of food poisoning, on prevention and first aid of emerging infectious diseases etc., the rates of awareness were 65.04%, 62.92%, 43.62% and 18.79% respectively. Proportions of households which had the first aid supplies were:first aid medicine box as 56.08%; fire extinguisher as 43.60%; spare water and food as 39.40%; having facilities as ropes, whistles and smoke masks for escape were all less than 15%. Rates of awareness on the following items as: correct use of gas switch as 81.52%, knowing the location of the circuit with gear and the fire hydrant as 74.39% and 35.98% , respectively. The correct disposal rates of the residents on the following items were:electric shock and falls (89.63%), patients of infectious diseases (83.31%), gas poisoning (82.98%), suspected symptoms on infectious diseases(82.66%), explosion and burns (66.78%), scald (62.72%)and sprain (57.05%). Scores on the related abilities were as follows: emergency(7.65, out of 10 points), escape(3.55, out of 5 points), self- and mutual medical aids (10.71, out of 16 points). Proportions of having learned and applied of first aid techniques among residents on the following items were:artificial breathing, chest compressions and cardiopulmonary resuscitation were all less than 10%. Level of knowing the first aid techniques was correlated with age and culture of the residents (P < 0.05). CONCLUSION: Both consciousness on health emergency and the abilities on self- and mutual medical aids were low among the community public, suggesting that both the government and pubic should pay more attention to the role of the abilities on self- and mutual medical aids.