OBJECTIVEFindings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP-1) or plasma cell membrane glycoprotein 1 (PC-1) gene single nucleotide polymorphism (K121Q, rs1044498) and genetic susceptibility to obesity. However, such relationship is not reproduced by some currently available studies. In this context, the present study is aimed to quantitatively analyze the association of K121Q variant with obesity in all published case-control studies in European adult populations.

METHODSPublished literature from PubMed, EMBASE, and ISI web of science databases were retrieved. The studies evaluating the association of ENPP1/PC1 gene K121Q polymorphism with obesity were included, in which sufficient data were presented to calculate the odds ratio (OR) with 95% confidence intervals (CIs).

RESULTSTen case-control studies meeting the inclusion criteria identified a total of 24,324 subjects including 11,372 obese and 12,952 control subjects. The meta-analysis results showed a statistically significant association of K121Q with obesity [OR (95%CI): 1.25 (1.04-1.52) P=0.021] under a recessive model of inheritance (QQ vs. KK+KQ) without heterogeneity or publication bias.

CONCLUSIONSThe results from the present study have indicated that ENPP1/PC1 Q121 variant may increase the risk of obesity and that more well-designed studies based on a larger population will be required to further evaluate the role of ENPP1/PC1 gene K121Q polymorphism in obesity and other related metabolic syndromes.

Europe ; epidemiology ; Genetic Predisposition to Disease ; Humans ; Obesity ; epidemiology ; genetics ; Odds Ratio ; Phosphoric Diester Hydrolases ; genetics ; Polymorphism, Genetic ; Pyrophosphatases ; genetics ; Risk Factors

Accompanied by the rapid improvement of clinical diagnosis and treatment technology and the needs of scientific research, the training of higher professional talents represented by breast surgery postgraduates is facing many challenges. Based on the above background, this study puts forward the new teaching mode combining online and offline, involving evidence-based medicine guidelines, strengthening the aesthetic concept and humanistic teaching quality into the breast surgery teaching system to improve the teaching concept and teaching mode. Through the intuitive information teaching means and clinical case analysis, the students' independent learning and thinking ability can be cultivated. Finally, we look forward to improving the scientific research level and the cultivation of breast surgeons with outstanding comprehensive ability and medical humanistic quality from the optimization of teaching modes.

Objective:This study introduces a novel approach utilizing a self-made drug delivery cannula implanted into the cerebellomedullary cistern(CMC)of rats to allow repeated administrations in conscious subjects.Methods:A self-made medication cannula is inserted through a drilled hole at the midpoint of the occipital crest of the rat's skull,de-scending along the inner wall of the occipital bone until reaching the CMC,and securing it in place with skull screws and self-curing resin.Lipopolysaccharide(LPS)is injected into the CMC to induce neuroinflammation,and the feasibility of this method is assessed using X-ray imaging,behavioral testing,and immunofluorescence staining.Results:The place-ment of the brain cannula was confirmed using X-ray film and pontamine sky blue staining.Rats in the LPS group exhib-ited a lower facial mechanical pain threshold compared to the Control group(P＜0.001),along with reduced residence time in the open field center(P＜0.01).Immunofluorescence staining revealed LPS-induced activation of caudal spinal trigeminal nucleus(SpVc)microglia.Conclusion:This method proves to be suitable for multiple administrations to the cerebellomedullary cistern of conscious rats,enabling the study of the SpVc's role in pain modulation.

Objective To explore the core acupoints and compatibility rules of acupuncture and moxibustion for epilepsy by using complex network method.Methods A prescription database was es-tablished through inclusion and exclusion criteria for searching literatures for databases from China Na-tional Knowledge Infrastructure,VIP,Wanfang,Web of Science,EMBASE,and Pubmed.SPSS Modeler software was used to analyze the frequency and correlation of acupoints,and Gephi0.10.1 software was used to establish a complex network model to explore the core acupoints and acupoint se-lection rules of prescriptions for epilepsy.Results Ultimately,144 valid literatures were included,199 prescriptions were extracted,involving 102 acupoints.Baihui acupoint had the highest frequency of use,specific acupoints were mainly Five-shu acupoint,the Eight Meridian Intersection acupoint,and the Back-shu acupoint.In selection of meridians,most acupoints were selected from governor me-ridian.Association rule analysis showed that Baihui-Taichong had the highest level of support and con-fidence.The analysis of complex network topology showed that 36 acupoints such as Baihui,Dazhui,Yaoqi and Fenglong were the core acupoints in the treatment of epilepsy by acupuncture and moxibus-tion.The analysis of acupoint communities revealed three major acupoint groups including governor meridian passing through treatment group,far and near matching acupoint group of the four limbs and head,and differentiation group of Zang-fu and body fluid for epilepsy treatment.Conclusion Acu-point compatibility of epilepsy by acupuncture and moxibustion should be mainly based on principle of the governor meridian combined with the differentiation of viscera and body fluid,and attention should be paid to distal-proximal point association.

Objective To explore the core acupoints and compatibility rules of acupuncture and moxibustion for epilepsy by using complex network method.Methods A prescription database was es-tablished through inclusion and exclusion criteria for searching literatures for databases from China Na-tional Knowledge Infrastructure,VIP,Wanfang,Web of Science,EMBASE,and Pubmed.SPSS Modeler software was used to analyze the frequency and correlation of acupoints,and Gephi0.10.1 software was used to establish a complex network model to explore the core acupoints and acupoint se-lection rules of prescriptions for epilepsy.Results Ultimately,144 valid literatures were included,199 prescriptions were extracted,involving 102 acupoints.Baihui acupoint had the highest frequency of use,specific acupoints were mainly Five-shu acupoint,the Eight Meridian Intersection acupoint,and the Back-shu acupoint.In selection of meridians,most acupoints were selected from governor me-ridian.Association rule analysis showed that Baihui-Taichong had the highest level of support and con-fidence.The analysis of complex network topology showed that 36 acupoints such as Baihui,Dazhui,Yaoqi and Fenglong were the core acupoints in the treatment of epilepsy by acupuncture and moxibus-tion.The analysis of acupoint communities revealed three major acupoint groups including governor meridian passing through treatment group,far and near matching acupoint group of the four limbs and head,and differentiation group of Zang-fu and body fluid for epilepsy treatment.Conclusion Acu-point compatibility of epilepsy by acupuncture and moxibustion should be mainly based on principle of the governor meridian combined with the differentiation of viscera and body fluid,and attention should be paid to distal-proximal point association.

Uranium is an important radioactive actinide in nature and an important nuclear material in nuclear industry. After uranium is accidentally released into the environment, it enters the body through the respiratory tract, the digestive tract, and other ways, then enters the circulation system through blood, and is finally mainly deposited in the kidney and bone, causing a certain degree of toxicity. Therefore, efficient low-toxicity chelators are an important way to reduce radionuclide pollution, radiation damage, and chemical toxicity. This article reviews uranium deposition and harm, the detoxification mechanism of uranium chelators, and the research advances in uranium chelators and points out the development trend of uranium chelators.

Objective:To evaluate the efficacy and safety of heating physiotherapy goggles in the treatment of meibomian gland dysfunction (MGD).Methods:A randomized controlled study was performed.Forty-four MGD patients were recruited in Wenzhou Medical University Eye Hospital from July 2021 to January 2022.Two patients were lost to follow-up.The patients were randomly divided into experimental group treated with heating physiotherapy goggles and control group treated with hot towels according to the random envelope method, with 21 patients (21 eyes) in each group.Throughout the study, the examiner was blinded.The data of the worse eye were analyzed.At baseline, 2 weeks and 4 weeks after treatment, the Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), fluorescein breakup time (FBUT), corneal fluorescein staining score (CFS), lid margin hyperemia score and meibomian gland function scores were measured to evaluate the efficacy; visual acuity, intraocular pressure and slit lamp microscopy were examined to assess the safety.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Wenzhou Medical University Eye Hospital (No.2021-177-K-153-01).Results:There were significant differences in OSDI scores between before and after treatment ( Ftime=16.528, P<0.001). No significant difference was found in OSDI scores between 30.46±17.31 at 2 weeks after treatment and 35.43±18.22 before treatment in control group ( P=0.405). The OSDI score at 2 weeks after treatment was 26.27±16.47, which was significantly lower than 39.24±17.96 before treatment in experimental group ( P=0.001). The eyelid margin hyperemia score was 0.0(1.0, 2.0) at 4 weeks after treatment in experimental group, which was significantly lower than 2.0(1.0, 3.0) in control group (Wald χ2=11.444, P=0.001). The morphologic scores of meibomian gland orifices at 2 and 4 weeks after treatment were both 1.0(0.0, 1.0) in experimental group, which were significantly lower than 2.0(1.0, 3.0) and 2.0(1.0, 2.5) in control group (Wald χ2=15.082, 23.172; both at P<0.001). The scores of meibum quality at 2 and 4 weeks after treatment were 1.0(0.5, 2.0) and 1.0(0.0, 1.5) in experimental group, which were significantly lower than 2.0(1.0, 2.0) and 2.0(1.0, 2.5) in control group (Wald χ2=4.638, 9.395; both at P<0.05). The scores of upper meibomian gland expressibility at 2 and 4 weeks after treatment were both 2.0(1.0, 2.0) in experimental group, which were significantly lower than 3.0(2.0, 3.0) and 2.0(2.0, 2.5) in control group (Wald χ2=6.489, 11.562; both at P<0.05). The score of lower meibomian gland expressibility at 4 weeks after treatment in experimental group was 1.0(0.5, 2.0), which was significantly lower than 2.0(2.0, 3.0) in control group (Wald χ2=24.085, P<0.001). The FBUT at 2 and 4 weeks after treatment were 3.00(1.75, 3.50) and 3.00(2.00, 4.00) seconds in experimental group, which were significantly longer than 1.00(0.75, 2.00) and 2.00(1.00, 3.00) seconds in control group (Wald χ2=8.576, 8.539; both at P<0.05). There were significant differences in TMH among different time points ( Ftime=8.874, P<0.001). In control group, the TMH at 4 weeks after treatment was (0.24±0.09) mm, which was significantly higher than (0.18±0.05) mm before treatment ( P<0.05). In experimental group, the TMH at 4 weeks after treatment was (0.23±0.09) mm, which was significantly higher than (0.17±0.05) mm before treatment ( P<0.05). Significant differences were found in CFS score among different time points (Wald χ2time=10.116, P=0.006). There was no statistically significant differences in CFS score between before and after treatment in control group (Wald χ2=1.781, P=0.410). In experimental group, the CFS scores at 2 and 4 weeks after treatment were 0.0(0.0, 1.5) and 0.0(0.0, 0.0), which were significantly decreased in comparison with 0.00(0.00, 4.00) before treatment (both at P<0.05). In experimental group, the visual acuity converted to the logarithm of the minimum angle of resolution at 2 and 4 weeks after treatment were 0.10(0.00, 0.22) and 0.10(0.00, 0.22), which was significantly better than 0.10(0.00, 0.40) before treatment (both at P<0.05). There was no significant change in intraocular pressure at different time points between the two groups ( Fgroup=0.432, P=0.515; Ftime=0.329, P=0.721). No serious adverse effects occurred in both groups during the follow-up period. Conclusions:Compared with hot towel therapy, the use of heating physiotherapy goggles can relieve ocular discomfort of MGD patients more rapidly and improve the function and status of the meibomian gland more significantly.Heating physiotherapy goggles can treat MGD safely and effectively.

Objective:To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low).Methods:A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups.Results:Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different ( P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group ( P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions:There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

According to the theory of qi channels， we explored the relationship of the method of invigorating blood and regulating tumour immunity， to provide ideas and methods for traditional Chinese medicine for regulating tumour immunity and anti-tumour metastasis. It is believed that qi channels are closely related to tumour immunity， and qi channels are equivalent to immune networks such as immune cells and immune factors with anti-tumour immunity in the tumour immune micro-environment. Combined with the physiological function and pathological characteristics of qi channels， it is proposed that the pathogenesis of qi channels-related disease due to qi channels failing to govern， blood stasis obstructing， and qi channels deficiency and stagnation as the basis for the occurrence of tumour immunosuppression and metastasis， and that qi channels constraint and stagnation as the condition for the occurrence of tumour immunosuppression and metastasis. In view of the pathomechanism of tumour immune escape caused by qi channels failing to govern， it is proposed that the therapeutic principle of regulating qi and channels to regulate tumour immunity by invigorating blood circulation method could be "performing functions when there is free flow， reaching the expectation when balanced"， and the key of treatment is to regulate qi and channels， unblock the collaterals to dispel stasis.

ObjectiveTo observe the distribution of traditional Chinese medicine （TCM） syndrome types in advanced pancreatic cancer patients， and explore the association between median survival time and different TCM syndromes and different intervention times of Chinese herbal medicine （CHM）. MethodsThe clinical data of 136 advanced pancreatic cancer patients who have received CHM for more than 3 months were collected retrospectively， including gender， age， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， western medicine treatment methods， TCM diagnosis and treatment information， and survival time. The Kaplan-Meier （KM） estimator was used， and the median survival time of patients was calculated. The TCM syndrome type of each patient was judged， and the main single syndrome types and compound syndrome types were summarized. The median survival time was compared among different compound syndrome types. The patients were further divided into the group of those having received CHM ≥6 months and those having received CHM ＜6 months. Whether receiving CHM ≥6 months was taken as the grouping variable， while the matching variables were age， gender， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， surgery， chemotherapy， and radiotherapy when propensity score matching was performed， and the difference in median survival time between the two groups of patients before and after matching was compared. ResultsFor 136 cases of advanced pancreatic cancer， the top five single syndromes were spleen qi deficiency， liver blood stasis， liver qi stagnation， spleen dampness， and liver heat. The main compound types were liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， liver constraint， qi stagnation and spleen deficiency syndrome， spleen-stomach yang deficiency and blood stasis syndrome， and spleen deficiency and dampness-heat internal accumulation syndrome. The overall median survival time before and after matching was 12.47 （7.70，17.10） months and 13.77 （8.83，17.20） months， respectively， and was significantly higher in the group treated with CHM ≥ 6 months than that treated with CHM ＜6 months （P＜0.05）. Among the 136 patients before matching， the median survival time of patients with spleen deficiency and dampness-heat internal accumulation syndrome was longest ［16.23 （14.17，19.40） months］， while that of patients with spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［7.33 （5.80，12.83） months］. For patients with liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， and spleen-stomach yang deficiency and blood stasis syndrome， those having received CHM ≥ 6 months have much longer median survival time than those having received CHM ＜6 months （P＜0.05）. Among the 108 patients after matching， the median survival time of those with spleen deficiency and dampness-heat internal accumulation syndrome was the longest ［15.23 （7.67，18.27） months］， while that of spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［8.80 （6.90，16.17） months］. For patients with liver-gallbladder dampness-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome， the median survival time was higher in the group treated with CHM ≥ 6 months treated with CHM ＜6 months （P＜0.05）. ConclusionAfter treatment with CHM， advanced pancreatic cancer patients with spleen deficiency and damp-heat internal accumulation had a better prognosis， while those with spleen-stomach yang deficiency and blood stasis had a worse prognosis. Treatment with CHM ≥ 6 months could extend the median survival of advanced pancreatic cancer patients with liver-gallbladder damp-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome.