The co-regulation of the gut microbiome and host genes might play essential roles in metformin gastrointestinal intolerance.

Metformin is commonly used, but approximately 20% of patients experience gastrointestinal intolerance, leading to medication discontinuation for unclear reasons and a lack of effective management strategies. In this study, the 18 fecal and blood samples were analyzed using 16S rRNA and mRNA transcriptome, respectively. These samples included 3 fecal and 4 blood from metformin-tolerant T2D patients before and after metformin treatment (T and Ta), 3 fecal and 5 blood from metformin-intolerant T2D patients before and after treatment (TS and TSa), and 6 fecal samples from healthy controls. The results showed that certain anti-inflammatory gut bacteria and gene, such as Barnesiella (p = 0.046), Parabacteroides goldsteinii (p = 0.016), and the gene JUND (p = 0.0002), exhibited higher levels in metformin-intolerant patients, and which decreased after metformin treatment (p < 0.05). This potentially invalidates patients' anti-inflammatory effect and intestinal mucus barrier protection, which may lead to alterations in intestinal permeability, decreased gut barrier function, and gastrointestinal symptoms, including diarrhea, bloating, and nausea. After metformin treatment, primary bile acids (PBAs) production species: Weissella confusa, Weissella paramesenteroides, Lactobacillus brevis, and Lactobacillus plantarum increased (p < 0.05). The species converting PBAs to secondary bile acids (SBAs): Parabacteroides distasonis decreased (p < 0.05). This might result in accumulation of PBAs, which also may lead to anti-inflammatory gene JUND and SQSTM1 downregulated. In conclusion, this study suggests that metformin intolerance may be attributed to a decrease in anti-inflammatory-related flora and genes, and also alterations in PBAs accumulation-related flora. These findings open up possibilities for future research targeting gut flora and host genes to prevent metformin intolerance.

LncRNA LINC01569 promotes M2 macrophage polarization to accelerate hypopharyngeal carcinoma progression through the miR-193a-5p/FADS1 signaling axis.

Background: Long non-coding RNA (lncRNA) LINC01569 plays an important role in regulating the tumor microenvironment (TME) and macrophage polarization. However, whether it participates in the progression of hypopharyngeal carcinoma by regulating the TME remains unclear. Methods: An online database was used to analyze clinical data. Macrophage polarization was detected using qRT-PCR and flow cytometry. In vivo experiments were performed using tumor-bearing nude mice. A co-culture system of hypopharyngeal carcinoma cells and macrophages was used to explore the interactions between the two cell types. Results: LINC01569 enhancement was observed in hypopharyngeal carcinoma tumor-associated macrophages (TAMs). In IL4-induced M2 macrophages, the expression of LINC01569 increased, while LINC01569 expression declined significantly in LPS-induced M1 macrophages. SiRNA-mediated downregulation of LINC01569 inhibits IL4-induced M2 macrophage polarization. Using online databases and a dual-luciferase reporter, miR-193a-5p was confirmed as a potential downstream sponge of LINC01569. MiR-193a-5p expression decreased in IL4-mediated M2 macrophages, which was restored by LINC01569 downregulation. Additionally, LINC01569 inhibition-mediated blocking of M2 macrophage polarization was moderately abolished by transfection with the miR-193a-5p inhibitor. Fatty acid desaturase 1 (FADS1) was verified as a downstream target of miR-193a-5p, and LINC01569 downregulation-mediated inhibition of FADS1 was blocked by miR-193a-5p mimics. Importantly, LINC01569 downregulation-mediated decline in M2 macrophage polarization was abolished by miR-193a-5p mimics, which was further reversed by FADS1 knockdown. Implantation of a mixture of FaDu cells and IL4-induced macrophages promoted tumor growth and proliferation, which were abrogated by the knockdown of LINC01569 in macrophages. Using an in co-culture system of FaDu cells and macrophages in vitro, M2 macrophage-regulated cell growth and apoptosis of FaDu cells were found to be mediated by the LINC01569/miR-193a-5p signaling axis. Conclusion: LINC01569 is highly expressed in the TAMs of hypopharyngeal carcinoma. LINC01569 downregulation restrains macrophages from polarizing toward M2 through the miR-193a-5p/FADS1 signaling axis, thereby helping tumor cells escape inherent immune surveillance and promoting the occurrence and development of hypopharyngeal carcinoma.

High expression of BHLHE40 promotes immune infiltration and tumor progression in thyroid cancer.

Thyroid cancer (THCA) is a common malignancy of the endocrine system which threatens people's health and life quality. It is urgent to find the marker gene of THCA. BHLHE40 is a key gene involved in tumor malignant progression. However, the role of BHLHE40 in THCA remains unclear. In this study, 346 upregulated and 302 downregulated genes were found by analyzing the Gene Expression Omnibus database. BHLHE40 was upregulated in THCA. BHLHE40 and its related differentially expressed genes were involved in cell adhesion and differentiation in THCA. Moreover, BHLHE40 was also highly expressed in THCA cells and tissues. Downregulation of BHLHE40 inhibited cell growth and metastasis. Knockdown of BHLHE40 conditioned media retarded cell migration in M2 macrophages. In addition, knockdown of BHLHE40 inhibited CD206 and CD163 expression and decreased the secretion of interleukin-10 in M2 macrophage. Therefore, BHLHE40 has the potential to be used as a biomarker of immune infiltration and tumorigenesis in THCA.

[Treatment of displaced midshaft clavicle fracture with convolution method].

OBJECTIVE: To explore the clinical effects of convolution method in treating displaced midshaft clavicle fracture. METHODS: From January 2018 to July 2019, 32 patients (21 males and 11 females) with displaced midshaft clavicle fracture were treated, ranging in age from 18 to 65 years old, with a median age of 41.5 years old. Nineteen patients had fractures on the left side and 13 patients had fractures on the right side. The duration from injury to treatment ranged from 30 minutes to 5 days. The patients were treated with convolution method and repeated push and rotation of the affected upper limb, followed by external fixation of clavicle band. The reduction and healing of the fracture and the functional recovery of shoulder joint were observed. RESULTS: After operation, fracture reduction was evaluated by X ray film. Seven patients had an excellent result, 20 good and 5 fair. All the patients were followed up, and the duration ranged from 14 to 18 weeks. The mean Neer score was 89.75±6.88, which included pain score of 32.66±2.54, functional score of 26.44±2.91, range of motion score of 22.38±2.06, and anatomy score of 8.43±0.84;17 patients receive an excellent result, 14 good and 1 fair. CONCLUSION: The rotation method combined with the repeated pushing and rotating of the upper limb of the affected side can well reduce the displaced fracture of the middle clavicle. Bandage and clavicle band can be performed after reduction. Functional exercise runs through the whole course of treatment. Functional recovery of shoulder joint is good and satisfactory therapeutic effect is achieved.

The clinical characteristics and treatment for sudden sensorineural hearing loss with vestibular schwannoma.

The aim of this study is to analyze the clinical characteristics and treatment of sudden sensorineural hearing loss (SSNHL) patients with vestibular schwannoma (VS). The clinical features of the VS patients were explored by retrospectively analyzing the clinical data from 542 cases of SSNHL patients between January 2008 and March 2013. There were 10 cases (10 ears) diagnosed with VS in 542 cases of SSNHL patients (10 ears, 1.85 %), 3 males, 7 females, with a range of 28-57 years. Among all the cases, eight patients with abnormal ABR, ten with ear ipsilateral stapedius reflexes which were completely not elicited and seven patients with healthy ear contralateral stapedius reflexes which were completely not elicited. Neuromas were classified by Koos grades according to size (8 of grade I, 1 of grade II, 1 of grade IV). Eight small VS  patients were taken waiting and MRI therapy strategies. Meanwhile, we used glucocorticoid treatment and timely and short-term medication to improve the microcirculation of the inner ear for these patients. And four cases' hearing was improved. Some vestibular schwannomas have SSNHL as initial symptoms, especially the small ones in internal auditory canal. To prevent misdiagnosis or leak-diagnosis, MRI should be performed as a routine test for SSNHL, and ABR is sometimes necessary for SSNHL patients. It is also necessary to give appropriate treatment to protect hearing of the small vestibular schwannoma patients whose first symptoms are diagnosed as SSNHL in acute phase.

[A clinical analysis for sudden sensorineural hearing loss with acoustic neurinoma].

OBJECTIVE: Retrospectively analyzed the clinical data of sudden sensorineural hearing loss with acoustic neuroma. METHODS: The clinical data of 467 cases with sudden sensorineural hearing loss were collected between Jan, 2008 and Aug, 2012. Discussed the clinical data which were diagnosed as acoustic neuroma. RESULTS: In 467 cases of sudden sensorineural hearing loss, nine cases were diagnosed as acoustic neuromas (9 ears, 1.93%), two males and seven females, with a age range of 28 to 57 years. Among them, seven cases accompanied with tinnitus, seven cases with vertigo. The hearing results in nine cases, two cases were found to be mild, two were moderate, four were severe, and one was profound hearling loss respectively. Hearing was classified into five types according to audiogram shape (1 of up-sloping, 1 of down-sloping, 2 of mid-frequency, 1 of profound loss, 4 of flat audiogram). Eight cases had abnormal ABR, nine cases with ear ipsilateral stapedius reflex were completely not elicited, seven cases with health ear contralateral stapedius reflex were completely not elicited. Tumors were graded by Koos Grades according to size (7 of grade I, 1 of grade II, 1 of grade IV). Seven small acoustic neuroma was taken waiting strategies. Meanwhile, we use glucocorticoid and improve the microcirculation of the inner ear medication short-termly for these patients. Four patients' hearing were improved. CONCLUSIONS: The initial symptoms of some acoustic neuroma are sudden hearing loss, especially the small tumors in internal auditory canal. In order to prevent misdiagnosis, MRI and ABR should be performed as a routine test for sudden sensorineural hearing loss. It is necessary to give appropriate treatment to protecting hearing for the small acoustic neuroma patients whose first symptoms are diagnosed as sudden sensorineural hearing loss.