G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Objective This study aims to summarize the experience of constructing a national demonstration zone for in-tegrated prevention and control of chronic diseases in Dapeng New District,Shenzhen,in order to provide a reference for grassro-ots chronic disease management in various regions.Methods Employing literature review and case analysis and using material description and data analysis,the study summarized the experience of target management experience in a close-knit medical con-sortium and offered suggestions for building a chronic disease system.Results Through close-knit medical consortium and target management method,the primary medical resources in Shenzhen Dapeng New District were optimized,and multi-sectoral coopera-tion was facilitated.This resulted in an increase in the main index data of chronic disease prevention and control,with the propor-tion of primary diagnosis and treatment increasing from 31.69％to 57.29％.Additionally,the health literacy rate among resi-dents improved from 39.1％to 50.82％,and several assessments achieved the first place within the city.Conclusion Regions can establish a close-knit medical consortium to set common goals,guiding high-quality medical resources to the grassroots level.By employing target management,they can concentrate effects from various grassroots sectors to advance chronic disease manage-ment construction.

Complete androgen insensitivity syndrome(CAIS) is characterized by lack of androgen response in target organs due to androgen receptor dysfunction, resulting in feminized external genitalia. Individuals with CAIS are typically advised to live as females. This article reports a patient diagnosed with CAIS and gender dysphoria in adulthood. Following the removal of a left pelvic mass, pathology indicated cryptorchidism with a concurrent Leydig cell tumor. Genetic testing revealed a deletion mutation in exon 3 of androgen receptor gene. During follow-up, the patient underwent gender reassignment, transitioning socially from female to male. This case provides new insights into gender allocation for CAIS patients.

Objective:To introduce a reliable and easy method of philtrum crest and philtrum repairing in secondary repair of cleft lip.Methods:Lift the upper lip flap after removing the scar on upper lip. Then the superficial orbicularis oris muscle was carefully separated, which formed the abnormal muscular eminence in the affected side after the first cleft lip repair. The pedicle of the orbicularis oris muscle the reconstructing philtrum crest. The lingual orbicularis oris muscle flap was lifted and curled from outside. The superficialorbicularis oris muscle was cut in philtrum longitudinally and turned outward. The two evertedorbicularisoris muscle flaps were sutured on both sides and fixed them on the reconstructing philtrum crest. The exposed deep orbicularis oris muscle in philtrum was sutured with the upper dermis, which formed the prominentphiltrum crest and deeper philtrum.Results:We reviewed the hospital records of patients from July 2008 to November 2021. In total, 201 patients were included in this study. All of these patients underwent the reconstruction of philtrum crest and philtrum with orbicularis oris muscle intertangling and philtrum plasty in secondary cleft lip repairing. During the treatment, the patients had no complications such as infection, hematoma and flap necrosis.198 patients were observed from 1 months to 36 months (7.8 months on average). All of them improved in different degrees in early postoperative period. Most reconstructed philtrum crest was raised and basically symmetrical with the contralateral side in shape. The philtrum was clear and the scar was not obvious. The reconstructed philtrum crest would decrease with time. 91.7% (90/98) patients were satisfied with the postoperative effects after three months.Conclusions:The method of reconstruction of philtrum crest and philtrum with orbicularis oris muscle intertangling and philtrum plasty in secondary cleft lip repairing is safe and effective. The long term postoperative effect is stable with high satisfaction as well. As a result, this method can be used as the philtrum crest and philtrum correction scheme for secondary cleft lip repairing.

Microbial induced calcium carbonate precipitation (MICP) refers to the natural biological process of calcium carbonate precipitation induced by microbial metabolism in its surrounding environment. Based on the principles of MICP, microbial cement has been developed and has received widespread attention in the field of biology, civil engineering, and environment owing to the merits of environmental friendliness and economic competence. Urease and carbonic anhydrase are the key enzymes closely related to microbial cement. This review summarizes the genes, protein structures, regulatory mechanisms, engineering strains and mutual synergistic relationship of these two enzymes. The application of bioinformatics and synthetic biology is expected to develop biocement with a wide range of environmental adaptability and high performance, and will bring the MICP research to a new height.
Calcium Carbonate/metabolism* ; Chemical Precipitation ; Urease/metabolism*

Objective:To investigate therapeutic effect of cisplatin sequential recombinant human vascular endostatin thoracic perfusion in treatment of malignant pleural effusion.Methods:A total of 80 patients with malignant pleural effusion in Maoming People's Hospital from January 2018 to February 2021 were enrolled, and all patients were divided into 2 groups according to the random number table methods, each group with 40 cases. The control group was treated with small-bore catheter minimally invasive drainage combined with cisplatin thoracic perfusion, and the study group was treated with small-bore catheter minimally invasive drainage combined with cisplatin sequential recombinant human vascular endostatin thoracic perfusion. And then the clinical efficacy, expressions of vascular endothelial growth factor (VEGF) expression, pain degree and adverse reactions were compared of both groups.Results:The treatment efficacy rate of the study group was higher than that of the control group [90% (36/40) vs. 75% (30/40)], and the difference was statistically significant ( χ2 = 5.04, P < 0.05). After treatment, the level of VEGF in pleural fluid and serum of the study group was lower than that of the control group [(304±106) pg/ml vs. (598±159) pg/ml,(103±43) pg/ml vs. (189±49) pg/ml], and the difference was statistically significant ( t = 6.62, P < 0.001; t = 6.23, P < 0.001). After treatment, the visual analogue scale (VAS) score of the study group was lower than that of the control group [(3.7±0.3) scores vs. (4.4±0.7) scores], and the difference was statistically significant ( t = 2.10, P < 0.05). The incidence of adverse reactions including stethalgia, fever, nausea and vomiting in both groups had no statistically significant differences (all P > 0.05). Conclusions:Cisplatin sequential recombinant human vascular endostatin thoracic perfusion combined with small-bore catheter minimally invasive drainage can effectively ameliorate clinical symptoms, inhibit the expression of VEGF, and alleviate pain degree with no serious adverse reactions in patients with malignant pleural effusion.

Objective:To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm.Methods:A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results:The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively.Conclusions:LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

OBJECTIVE: To analyze the hematological phenotypes of Hb J-Bangkok and concomitant thalassemia. METHODS: In total 72 397 samples were screened by using capillary electrophoresis. Samples with Hb J-Bangkok were identified by DNA sequencing and analysis of red blood cell parameters. Gap-PCR and PCR-reverse dot blotting (PCR-RDB) were used for analyzing the thalassemia genes. RESULTS: Thirty one cases of Hb J-Bangkok were identified, all of which were heterozygotes. The hematological phenotype index (Hb, mean corpuscular volume, mean corpuscular hemoglobin, Hb J-Bangkok, Hb A CONCLUSION Hb J-Bangkok heterozygotes have normal hematological phenotypes, though they may show different hematological characteristics when concomitant with different types of thalassemia, for which genetic counseling should be provided accordingly.
Female ; Hemoglobins, Abnormal/genetics* ; Heterozygote ; Humans ; Male ; Phenotype ; Thailand ; beta-Thalassemia/genetics*

Objective:To investigate the efficacy of sequential mechanical ventilation based on pulmonary infection control window in the treatment of severe pneumonia complicated by respiratory failure in children.Methods:A total of 300 children with pneumonia complicated with respiratory failure who received mechanical ventilation in Jiande Second People's Hospital from January 2016 to December 2017 were included in this study. They were assigned to receive either conventional continuous invasive mechanical ventilation (control group, n = 150) or invasive- noninvasive sequential mechanical ventilation based on pulmonary infection control window (observation group, n = 150) according to the order of admission. Invasive ventilation time, intensive care unit stay, expiratory time, inspiratory time and time to peak tidal expiratory flow, blood gas analysis indexes, incidence of ventilator-associated pneumonia, pulmonary hemorrhage and pneumothorax were compared between the two groups. Results:After treatment, PaO 2 value [(97.31 ± 6.39) mmHg vs. (86.24 ± 10.92) mmHg], PaO 2/FiO 2 [(280.78 ± 40.12) mmHg vs. (210.75 ± 40.11) mmHg], pH value [(7.44 ± 0.01) vs. (7.27 ± 0.04)], expiratory time [(1.18 ± 0.12) s vs. (0.89 ± 0.11) s], inspiratory time [(0.79 ± 0.09) s vs. (0.39 ± 0.09) s], time to peak tidal expiratory flow [(0.41 ± 0.02) s vs. (0.21 ± 0.03) s] and the rate of successful weaning (96.67% vs. 78.67%) in the observation were significantly higher than those in the control group ( t = 13.287, 130.381, 9.231, 6.353, 9.793, 10.131, χ2 = 22.475, all P < 0.001). After treatment, PaCO 2 value [(39.76 ± 5.49) mmHg vs. (46.72 ± 7.51) mmHg], invasive ventilation time [(8.11 ± 3.21) d vs. (17.24 ± 4.52) d], intensive care unit stay [(15.03 ± 2.94) d vs. (21.94 ± 4.29) d], the proportion of children having ventilator-associated pneumonia (1.33% vs. 6.67%), the proportion of children having pulmonary hemorrhage (0.00% vs. 2.67%) and the proportion of children having pneumothorax (2.67% vs. 8.00%) in the observation group were significantly higher than those in the control group ( t = 14.798, 10.136, 9.962, χ2 = 5.556, 4.054, 4.225, all P < 0.05). Conclusion:Sequential mechanical ventilation based on pulmonary infection control window for the treatment of severe pneumonia complicated by respiratory failure in children can achieve good curative effects through greatly improving blood gas index and is highly safe.

Objective:To evaluate the value of the crescent sign for predicting the invasiveness of lung adenocarcinoma presenting as pure ground-glass nodule (pGGN).Methods:The clinical, pathological and imaging data of 316 patients (320 pGGNs) confirmed lung adenocarcinoma by surgery and pathology from July 2013 to June 2018 in the First Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. All pGGNs were divided into preinvasive group (148 pGGNs) and invasive group (172 pGGNs) according to histopathology. Logistic regression analysis was used to determine the risk factors for invasiveness of pGGN, and the ROC curve analysis was performed on each risk factor.Results:Crescent sign was found in 24 cases (16.2%) in the preinvasive group and 49 (28.5%) in the invasive group, and the difference between the two groups was statistically significant (χ2=6.804 ,P=0.009).There were statistically significant differences in patient′s age, lesion size, shape, lobulation sign, and vascular stretch sign between the two groups ( P<0.05). The ROC curve showed that with the lesion size 10.5 mm as the optimal cut off value, the sensitivity for differential diagnosis of preinvasive and invasive lesions was 65.7%, the specificity was 61.5%, and the area under the curve was 0.666. Logistic regression analysis showed that maximum diameter of the lesion ≥10.5 mm, irregular shape, crescent sign and vascular stretch were independent risk factors of invasiveness of pGGN, and the OR value (95%CI) were 3.192 (1.981-5.144), 3.672 (1.545-8.725), 1.972 (1.104-3.521), and 2.026 (1.087-3.777), respectively. A logistic model was established based on the above four independent risk factors, and the area under curve was 0.711 (95%CI 0.655-0.768). Conclusion:Crescent sign can effectively reflect the invasiveness of pGGN. Maximum diameter of the lesion ≥10.5 mm, irregular shape, crescent sign and vascular stretch sign are independent risk factors of invasiveness of pGGN.