Post-traumatic osteoarthritis (PTOA) is a chronic degenerative joint disease caused by joint injury and abnormal mechanical stress stimulation is one of its key mechanisms. Currently, it is difficult to repair the articular cartilage completely even with surgical treatment and there is a lack of effective treatments for PTOA. Chondrocytes, one of the primary cell types involved in the pathogenic process of PTOA, are highly sensitive to mechanical signals. The mechanosensitive ion channel Piezo1 serves the important functions of sensing external forces and mechanical stimuli and plays a crucial role in PTOA by regulating chondrocytes′ responses to mechanical stress. Therefore, its essential to understand the mechanisms of the Piezo1 channel in regulating PTOA chondrocytes in exploring new therapeutic strategies. To this end, the authors reviewed the research progress on the regulatory mechanisms of the Piezo1 channel on PTOA chondrocytes, aiming to provide a reference for future studies on PTOA mechanisms and treatment options.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To investigate the effect of ANXA on biological behavior of papillary thyroid carcinoma (PTC) cells by interfering with the expression of annexin A1 (ANXA1) in PTC cell lines by short hairpin RNA (shRNA) .Methods:The shRNA with specific and high efficiency was designed to specifically interfere with the expression of ANXA1 in TPC-1 and BCPAP cell lines, and transfect the TPC-1 and BCPAP cell lines respectively, including specific ANXA1 interference and negative control virus transfection, and they were divided into shANXA1 group and negative control virus group. Semi-quantitative reverse transcription PCR (Q-PCR) and Western Blot were employed to verify gene expression. The shANXA1 group was used as the experimental group, the untransfected virus group and the negative control virus group were set as the control groups. The expression levels of ANXA1 in the three groups were compared and the shRNA interference efficiency was verified. The effects of ANXA1 knockdown on the proliferation, migration and invasion of TPC-1 and BCPAP cell lines were investigated by scratch, CCK8 and Transwell invasion experiments. Independent sample t test was used to compare the means between the two groups, and one-way analysis of variance was employed to compare multiple groups, with P<0.05 as statistically significant. Results:shRNA could efficiently silence the expression of ANXA1 at the transcription and translation level in PTC cell lines. Compared with the negative control cells, the cells proliferated after successful lentiviral transfection of TPC-1 and BCPAP (BCPAP, 24h: F= 25.15, P<0.001; 48h: F=6.44, P<0.001; 48h: F=46.94, P<0.001; TPC-1, 24h: F=207.50, P<0.001; 48h: F=202.45, P<0.001; 48h: F=55.89, P<0.001) , its migration (BCPAP, F=12511.10, P<0.001; TPC-1, F=3966.10, P<0.001) and invasion ability (BC-PAP: F=94.65, P<0.001; TPC-1: F=681.74, P<0.001) significantly decreased. Conclusion:After shRNA knock-down of ANXA1 gene, the proliferation, migration and invasion ability of TPC-1 and BCPAP cell lines decreased significantly, indicating that silencing this gene can reduce tumor aggressiveness, and initially reveals that ANXA1 may be an important potential in PTC biotherapy Target.

Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L ^-1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L ^-1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
Cell Movement ; Chemotaxis ; Equipment Design ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques ; Microfluidics ; Neutrophils ; Reproducibility of Results

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca

Robotic-assisted transanal total mesorectal excision (R-TaTME) has unique advantage in low rectal cancer. Single incision plus oneport (SIPOP) laparoscopic operation can synchronously cooperate with robotic-assisted transanal operation, in order to the difficulty of operation, improve the quality of operation and shorten the time of operation. A retrospective analysis was conducted on the clinical and pathological data of one patient who underwent SIPOP synchronously combined with R-TaTME + sigmoid-anal anastomosis + ileostomy at the Department of General Surgery, Army Characteristic Medical Center on September 11, 2019. This 71-year-old patient was male with body mass index of 24.08 kg/m 2 and received preoperative chemotherapy. Rectal adenocarcinoma was confirmed by colonoscopy biopsy, and distance from tumor lower edge to anal verge was 3 cm. MRI indicated T2N1 stage. The operation was completed successfully, and the transabdominal and robotic transanal surgery totaled 117 minutes, with 15 minutes for the robotic transanal preparation step. There was about 20 ml of intraoperative blood loss and no blood transfusion was performed. The patient was discharged 6 days after operation. No intraoperative or postoperative complications occurred. The postoperative TNM staging was stage I (pyT2N0cM0). No recurrence or metastasis was found at postoperative 7 month. It is a safe, effective and feasible technique for patients with low rectal cancer.

Robotic-assisted transanal total mesorectal excision (R-TaTME) has unique advantage in low rectal cancer. Single incision plus oneport (SIPOP) laparoscopic operation can synchronously cooperate with robotic-assisted transanal operation, in order to the difficulty of operation, improve the quality of operation and shorten the time of operation. A retrospective analysis was conducted on the clinical and pathological data of one patient who underwent SIPOP synchronously combined with R-TaTME + sigmoid-anal anastomosis + ileostomy at the Department of General Surgery, Army Characteristic Medical Center on September 11, 2019. This 71-year-old patient was male with body mass index of 24.08 kg/m 2 and received preoperative chemotherapy. Rectal adenocarcinoma was confirmed by colonoscopy biopsy, and distance from tumor lower edge to anal verge was 3 cm. MRI indicated T2N1 stage. The operation was completed successfully, and the transabdominal and robotic transanal surgery totaled 117 minutes, with 15 minutes for the robotic transanal preparation step. There was about 20 ml of intraoperative blood loss and no blood transfusion was performed. The patient was discharged 6 days after operation. No intraoperative or postoperative complications occurred. The postoperative TNM staging was stage I (pyT2N0cM0). No recurrence or metastasis was found at postoperative 7 month. It is a safe, effective and feasible technique for patients with low rectal cancer.

OBJECTIVE： To provide reference for perioperative prophylactic use of antibiotics in urinary surgery department. METHODS： In response to irrational perioperative prophylactic use of antibiotics in urinary surgery department， taking type Ⅱ incision surgery and special diagnosis and treatment and preventive drug use as an example， the management and control mode for perioperative prophylactic use of antibiotics was established and intervened in urinary surgery department so as to intervene in antibiotics use through formulating surgical type risk classification system， forming perioperative medication clinical pathways such as type Ⅱ incision surgery and urinary calculi surgery with different infection risk， establishing tracking and supervision mechanism. The rationality indexes of perioperative prophylactic medication such as the rate of prophylactic antibiotics use were compared among related medical records collected from urinary surgery department within 3 months before and after intervention （186 records before intervention， 179 records after intervention）. Antibiotics use density （AUD） and amount of antibiotics in urinary surgery department were compared within 3 months before and after intervention to evaluate management and control effect. RESULTS： Among surveyed medical records， compared with before intervention， the rate of prophylactic antibiotics use was decreased from 97.3％ （181/186） to 91.6％ （164/179）； the rate of rational drug selection was increased from 17.7％ （32/181） to 71.3％ （117/164）； correct rate of medication timing was increased from 9.9％ （18/181） to 32.3％ （53/164）； the rate of rational post-operative prevention course was increased from 17.1％ （31/181） to 37.2％ （61/164）， with statistical significance （P＜0.05 or P＜0.01）. Average AUD was deceased from 83 DDD to 70 DDD within 3 months after intervention， and the amount of antibiotics was decreased from 689 669.23 yuan to 531 040.11 yuan. CONCLUSIONS： Established management and control mode for perioperative prophylactic use of antibiotics in type Ⅱ incision surgery and special diagnosis and treatment and preventive drug use can effectively reduce the rate of prophylactic antibiotics， AUD and amount of antibiotics in urinary surgery department， and promote rational use of antibiotics during perioperative period.