To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.

Objective To analyze the status and risk factors of Helicobacter pylori (Hp) infection in permanent residents in a certain area. Methods The clinical data of 6 792 permanent residents surveyed from January 2021 to December 2023 were retrospectively analyzed. All subjects underwent 13C-urea breath test，and relevant general information was collected to analyze Hp infection status. According to whether Hp infection occurred, they were divided into positive group (n=4 283) and negative group (n=2 509). The differences in general information, living habits, and dietary habits between the two groups of subjects were analyzed, and multivariate logistic regression analysis was conducted. Results Among the 6 792 permanent residents surveyed from January 2021 to December 2023, 4283 were positive for 13C-urea breath test, accounting for 63.05% of the total. There were statistically significant differences in age distribution, gender, BMI, tableware cleaning, personal hygiene products use, chopsticks use, and raw food and vegetable cleaning between the positive group and the negative group (P<0.05). The single factors of Hp infection were substituted into multivariate logistic regression analysis equation, and it was found that age ≥45 years old, male, BMI≥24, no use of detergents to clean utensils, sharing personal hygiene products, not using public chopsticks, having a habit of eating raw food, and not cleaning vegetables before eating were independent risk factors for Hp infection. Conclusion The positive rate of Hp infection in this area is relatively high, and the infection factors are related to age, gender, and some lifestyle and dietary habits.

This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

ObjectiveTo assess the availability of bronchodilators for treatment of chronic obstructive pulmonary disease (COPD) in community health service centers (CHCs) in Shanghai. MethodsOn the basis of previous research, the questionnaire was updated, and surveys were conducted from April to May 2023 in CHCs in Shanghai, with a focus on the availability of medications for COPD treatment. According to the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug List (2023 Edition), a total of 24 types of bronchodilators for COPD treatment were identified. The availability rates were used to assess the accessibility of specific drugs in CHCs, and the dispensing rates were used to evaluate the variety of these medications in CHCs. ResultsA total of 248 CHCs responded, with a response rate of 100.0%. Among them, a total of 232 CHCs (93.5%) were equipped with bronchodilators. In terms of availability rates, the availability rates for β₂ adrenoreceptor agonists, muscarinic antagonists, combination drugs, and xanthines drugs were 86.3%, 52.0%, 52.4%, and 85.1%, respectively. Regional differences were observed, in that salbutamol/levalbuterol and budesonide-formoterol were less available in suburban CHCs, ipratropium bromide had lower availability in urban CHCs, and aminophylline was more available in suburban CHCs. Regarding the dispensing rates of the 24 types of bronchodilators for COPD treatment, the median of types equipped by CHCs was 5, with a total of 200 CHCs (80.6%) equipped with fewer than 7 types of bronchodilator drugs. ConclusionThe proportion of CHCs in Shanghai equipped with bronchodilators for COPD is relatively high. However, there exist problems such as limited variety of stocked medications, significant differences in the availability of different drugs, and regional imbalances in drug stocking. To improve the standardized diagnosis, treatment, and management of COPD patients, it is recommended to enhance the availability of COPD treatment medications in CHCs.

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective : To investigate the effects of cinnamaldehyde(CA) on the growth, metastasis and apoptosis of human endometriosis(EMs) cells and to explore whether the mechanism is related to ribosomal protein S7(RPS7) expression. Methods : Endometriosis cells were divided into control group, CA group, sh-NC group, CA+sh-RPS7 group. Effects of CA on cell growth in human endometriotic cells were determined using Cell Counting Kit-8(CCK-8) and colony formation assay. Effects of CA on cell metastasis were performed by motility assay and Transwell assay. Effects of CA on cell apoptosis were evaluated by Hoechst 33258 staining and flow cytometry. Meanwhile, the levels of PCNA, E-cadherin, Vimentin, Bax and Bcl-2 were evaluated using Western blot in human endometriotic cells with treatment CA. The expression of RPS7 was detected by qRT-PCR and Western blot assay. The RPS7 overexpression of human endometriotic cells was established by cell transfection. CA-mediated effects on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry in human endometriotic cells with RPS7 overexpression. Results : CA repressed cell growth as well as down-regulated PCNA. The half inhibitory concentration(IC50) value was 53.60 μmol/L after 24 h treatment, and colony formation rate was 25.32%. Additionally, CA inhibited metastasis which was associated with downregulated Vimentin and upregulated E-cadherin. The relative migration rates were 35% and 29% as well as invasion rate was 40%. Further, CA induced apoptosis by cell cycle G2/M phase arrest and cell apoptosis rate was 25.1%, which related to the up-regulation of of Bax and the down-regulation of Bcl-2. CA inhibited the expression of RPS7 and overexpression of RPS7 promoted cell proliferation and suppressed apoptosis in CA-mediated cells. Conclusion CA inhibits cell growth, metastasis, and induces cell apoptosis by downregulating the expression of RPS7.

ObjectiveTo evaluate the validity of four screening questionnaires on chronic obstructive pulmonary disease (COPD) among community residents in Shanghai, and to provide a scientific basis for selecting suitable screening questionnaires and plans for the community use. MethodsA multi-stage random sampling method was used to select community residents aged ≥40 for COPD questionnaire screening and spirometry. The screening questionnaires included the COPD Population Screener Questionnaire (COPD-PS), the COPD Screening Questionnaire (COPD-SQ), the COPD Diagnosis Questionnaire (CDQ), and the Lung Function Questionnaire (LFQ). The diagnostic gold standard for COPD was defined as a ratio of post-bronchodilator forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 0.7. The receiver operating characteristic (ROC) curve was used to assess the validity of each questionnaire, and DeLong’s test was used to compare the area under the curve (AUC) of different questionnaires. ResultsAmong the 1 122 residents screened, 99 (8.8%) were diagnosed with COPD based on the gold standard criteria. The AUC values for the four questionnaires ranged from 0.643 to 0.682, with no statistically significant differences in screening accuracy among them (P>0.05). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each questionnaire at recommended cut-off points were as follows: COPD-PS (sensitivity: 33.3%, specificity: 84.9%, PPV: 17.6%, NPV: 92.9%), COPD-SQ (34.3%, 85.8%, 19.0%, 93.1%), CDQ (73.7%, 42.4%, 11.0%, 94.4%), and LFQ (48.5%, 74.8%, 15.7%, 93.8%). Optimal cut-off values for this population differed from the recommended values. When selecting the optimal cut-off value, the sensitivity of COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%) increased, while the specificity of CDQ (75.9%) increased. The AUC of sequential lung function testing for all four screening questionnaires increased to 0.7 or above. The optimal cut-off values for the four questionnaires in this population differed from the recommended values. When applying the optimal cut-off values, the sensitivity of three questionnaires increased: COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%), while the specificity of CDQ rose to 75.9%. The AUC of each questionnaire increased to above 0.7 when followed by sequential lung function testing. ConclusionThe COPD-PS, COPD-SQ, CDQ, and LFQ have limited value for COPD screening among Shanghai community residents, indicating that further refinement of these tools is needed.

Objective Pulmonary oxygen poisoning resulting from hyperbaric oxygen,frequently occurs in specialized operations,without any current effective prevention or treatment measures.To elucidate the impact and mechanism of neostigmine(NEO)in combination with anisodamine(ANI)(neoscopolamine)on pulmonary oxygen toxicity.Methods The animal model of pulmonary oxygen poisoning was established.C57BL/6 mice were exposed to 2.5 ATA 99.9%oxygen for 6 h.The control group mice were injected with normal saline ip,while the treatment group mice received injections of ANI(25 mg/kg,ip)and NEO(50 μg/kg,ip).Lung tissues were collected and stained with HE to observe any pathological injuries after exposure.Evans blue stain was utilized to identify lung permeability,wet/dry lung ratio,and protein concentration in the bronchoalveolar lavage fluid(BALF)to assess the lung injury's severity.The modifications in inflammatory factors,oxidative stress indicators,and iron content in lung tissue were assessed.Results The results showed that the 2.5 ATA 99.9%oxygen-exposed group experienced a significant worsening of lung injury,as well as increased lung permeability,lung wet/dry ratio,and protein content in alveolar lavage fluid when compared to the control group.Moreover,mRNA levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,and IFN-γ in the lung tissue of the model group were significantly elevated,while the levels of anti-inflammatory cytokines IL-4 and TGF-β were significantly reduced.The oxidative index MDA also significantly increased,while the antioxidant index GSH significantly decreased.Additionally,the expression of GPX4,a marker of ferroptosis,increased with an increase in iron content.Neoscopolamine treatment successfully reversed those effects.Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning.Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway,thereby reducing the content of free iron in lung tissue and finally inhibiting cell ferroptosis.

Objective:To analyze the three-dimensional radiographic characteristics of calcifying odon-togenic cyst and calcifying epithelial odontogenic tumor using spiral computed tomography(CT)and cone-beam computed tomography(CBCT).Methods:Clinical records,histopathological reports,and CBCT or non-enhanced spiral CT images of 19 consecutive patients with calcifying odontogenic cyst(COC)and 16 consecutive patients with calcifying epithelial odontogenic tumor(CEOT)were retrospec-tively acquired,and radiographic features,including location,size,expansion,internal structure and calcification,were analyzed.Results:Among the 19 COC cases(12 males and 7 females,with an average age of 27 years),89.5％(17/19)of the lesions originated from the anterior and premolar areas,100.0％of them exhibited cortex expansion,and 78.9％had discontinued cortex.Among the 16 CEOT cases(3 males and 13 females,with an average age of 36 years),81.3％(13/16)of the lesions were in the premolar and molar areas,56.3％of them exhibited cortex expansion,and 96.8％had discontinued cortex.According to the distribution of internal calcifications,these lesions were divided in-to:Ⅰ(non-calcification type):absence of calcification;Ⅱ(eccentric marginal type):multiple calcifi-cations scattered along one side of the lesion;Ⅲ(diffused type):numerous calcifications diffusely dis-tributed into the lesion;Ⅳ(plaque type):with a ≥ 5 mm calcified patch;V(peri-coronal type):multiple calcifications clustered around impacted teeth.Calcifications were present in 73.7％of COC le-sions,including 9 type Ⅱ,3 type Ⅲ and 2 type Ⅳ lesions,and 42.8％of CEOT lesions had calcifica-tion images,including 2 type Ⅲ and 5 type V lesions.Six COC lesions had odontoma-like images.Moreover,8 of 9 type Ⅰ CEOTs were histologically Langerhans cell-rich subtype,which had a smaller size(with an average mesiodistal diameter of 17.8 mm)and were not associated with impacted teeth.Conclusion:COC lesions tended to originate from the anterior part of the jaw and exhibit cortex expan-sion,and were sometimes associated with odontoma.CEOT commonly occurred in the posterior jaw and had discontinued cortex.Two lesions had significantly different calcification map.Over 70％of COC le-sions had calcification images,which were mostly scattered along one side of the cysts,far from the im-pacted teeth.Approximately 60％of CEOT lesions exhibited smaller size and non-calcification,and the remaining CEOT cases often had calcification images clustered around the impacted teeth.