Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.

OBJECTIVE To investigate the effects of Tongxie yaofang （TXYF） on the symptoms of rats with irritable bowel syndrome with diarrhea （IBS-D） by regulating colonic tryptophan hydroxylase 1 （TPH1）， serotonin transporter （SERT） and intestinal flora. METHODS Forty-two SD rats were randomly divided into control group （7 rats） and modeling group （35 rats）. In modeling group， rat model of IBS-D was established by intragastrical administration of 0.45 g/L senna leaf solution [10 mL/（kg·d）] combined with chronic unpredictable stimulation. Thirty-five successfully modeled rats were randomly divided into model group， pinaverium bromide group [15 mg/（kg·d）] and TXYF low-dose， medium-dose and high-dose groups [3.75、7.5、15 g/（kg·d）， calculated by crude drug]， with 7 rats in each group. Each administration group was orally administered the corresponding drug， once a day， for 10 consecutive days. The general condition and weight changes of each group of rats were compared before modeling， after modeling and before administration， after the last drug intervention； the diarrhea index and visceral sensitivity were detected， and pathological changes of colon tissue were observed after modeling and before administration， after the last drug intervention. The level and expression of 5-hydroxytryptamine （5-HT）， protein and mRNA expressions of TPH1 and SERT were determined in colon tissue. The diversity and structural changes of fecal intestinal flora of rats were analyzed. RESULTS There was no significant change in colon histopathology in each group. Compared with model group， the general condition of rats in each medication group improved. The daily body weight gain of rats was significantly increased， while diarrhea index， visceral sensitivity， the expressions of 5-HT and TPH1 in colon tissue were significantly decreased； SERT expression of colon tissue was significantly increased in TXYF medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The diarrhea index， colon TPH1 protein expression and colon 5-HT protein positive rate in the TXYF low-dose group decreased while the mRNA expression of SERT increased significantly （P＜0.05）. There was a dose- dependent trend in the effect of TXYF. Compared with model group， Chao1 index and Shannon index of the rats in TXYF high- dose group were significantly decreased （P＜0.05 or P＜0.01）， the beneficial bacteria such as Firmicutes and Lactobacillus increased significantly， while the pathogenic bacteria such as Proteobacteria， Escherichia-Shigella and Rikenellaceae_RC9_gut_ group decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS TXYF can decrease the level of 5-HT and improve intestinal flora disorder by inhibiting the expression of TPH1 and up-regulating the expression of SERT in colon tissue， thus promoting the symptoms of IBS-D rats.

Objective To explore the value of non-contrast CT findings of acute ischemic stroke(AIS)for predicting early prognosis after mechanical thrombectomy.Methods Data of 161 AIS patients from clinical center 1 who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into training set(n=113)and internal test set(n=48)at the ratio of 7∶3,while 79 AIS patients who underwent mechanical thrombectomy from clinical center 2 were retrospectively enrolled as external test set.According to the National Institutes of Health stroke scale(NIHSS)scores 7 days after thrombectomy,patients'prognosis were classified as good(＜15 points)or poor(≥15 points).Pre-treatment non-contrast CT images of patients were reviewed,and CT findings were comparatively analyzed.Independent predictors of patients'early prognosis after mechanical thrombectomy were obtained with sequential univariate and multivariate logistic regressions,and a predicting model was established and visualized as a nomogram.The receiver operating characteristic curve was drawn,and the distinction was assessed with the area under the curve(AUC),then calibration was assessed with Hosmer-Lemeshow goodness of fit test,and the net benefit was evaluated with decision curve analysis(DCA).Results Alberta stroke program early CT score(ASPECTS),hyperdense middle cerebral artery sign(HMCAS)and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy(all P＜0.05).The predictive model was established combining the above 3 variables and then visualized as a nomogram to predict prognosis of AIS after mechanical thrombectomy,with AUC of 0.776 in internal test set(χ2=6.052,P=0.417)and 0.800 in external test set(χ2=2.269,P=0.811).DCA showed that the nomogram might provide clinical net benefit within certain threshold probability ranges.Conclusion ASPECTS,HMCAS and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy.The nomogram originated from predicting model combining the three could be used to somewhat accurately predict poor early prognosis after mechanical thrombectomy.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Objective:To report the clinical, electrophysiological and genetic features in a Chinese family with distal hereditary motor neuropathy type V (dHMN-V) and screen the pathogenic mutant gene.Methods:A family with the history of inherited peripheral neuropathy was recruited in the First Affiliated Hospital of Zhengzhou University in July 2017. The clinical features and electrophysiological data were investigated. Genetic testing on well-established genes associated with hereditary peripheral neuropathy was conducted by targeted high throughput sequencing and the candidate variant was screened in the family and normal controls.Results:There were four affected individuals in the family. The proband, a 25-year-old male, was characterized by weakness and atrophy in the distal extremities primarily affected the upper extremities without sensory impairment. Electrophysiological study showed chronic neurogenic pattern in the upper and lower limb muscles. The motor conduction showed reduced velocity and compound muscle action potential amplitude, while the sensory conduction studies results were normal. The grandfather, a maternal uncle and a cousin of the proband exhibited similar clinical manifestations and electrophysiological abnormality. Genetic testing revealed a heterozygous mutation, c.880G>A(p.G294R), in the GARS gene in the proband. Proband′s mother and two other affected individuals carried the mutation which was confirmed by Sanger sequencing. The mutation site was not found in the unaffected members from the family and 300 unrelated normal controls. The variant is a novel mutation which has not been reported in dbSNP, ExAC and 1000 Genomes Project databases. Conclusion:The results suggest that the novel c.880G>A(p.G294R) mutation of the GARS gene is responsible for the Chinese patients with dHMN-V, and the findings broaden the mutational spectrum of GARS gene.

Objective:To investigate the damage and mechanism of artemisia annua pollen on tight junction of human nasal mucosa epithelial cells (HNEpC).Methods:HNEpC were cultured in vitro. Different concentrations of artemisia annua pollen (0, 20, 40, 80, 100, 160, 200 μg/ml) were used to intervene the cells for 24 h, and the cell proliferation activity was detected by the CCK-8 method. The expression and phosphorylation of p38MAPK signaling pathway were detected by Western Blot before and after the intervention of SB203580, a p38MAPK inhibitor in HNEpC. Immunofluorescence chemical staining, Western Blot and quantitative real-time PCR (qPCR) were used to observe the expression and distribution of tight junctions Occludin and Claudin-1. SPSS 21.1 software was used for statistical analysis.Results:CCK-8 results showed that, compared with the control group, the proliferation activity of HNEpC increased after 6 h intervention with different concentrations of artemisia annua pollen (all P<0.05). After 12 h of intervention, the proliferation activity of HNEpC in the 20, 40, 80, 100 and 160 μg/ml groups was not significantly changed (all P>0.05), while that in the 200 μg/ml group was decreased ( P<0.05). After the intervention for 24 h, the proliferation activity of cells in the 20 and 40 μg/ml groups was not significantly changed (all P>0.05), while that in the 80, 100, 160 and 200 μg/ml groups was decreased (all P<0.05). Immunofluorescence staining showed that the Occludin and Claudin-1 proteins in the normal control group were localized on the cell membrane and expressed more and formed a ring structure around the cell membrane. However, under the intervention of high concentration artemisia annua pollen, its expression level decreased, appeared broken, fuzzy, and nonuniform distribution. Western Blot and qPCR results showed that after 24 h of intervention, the expression levels of HNEpC Claudin-1 protein and its mRNA in the pollen groups (40, 80, 100, 160, 200 μg/ml) of artemisia annua decreased compared with those of those of the control group (mRNA expression levels were 0.567±0.214, 0.443±0.109, 0.462±0.160, 0.497±0.134, 0.388±0.076 compared with 1.001±0.067, respectively, all P<0.05). However, the mRNA of Occludin protein and its mRNA only decreased in the 200 μg/ml treatment group (mRNA expression level was 0.631±0.109 compared with 1.016±0.026, P<0.05), while all the other treatment groups increased (mRNA expression levels were 1.258±0.134, 1.827±0.103, 2.429±0.077, 1.707±0.085, 1.477±0.066 compared with 1.016±0.026, respectively, all P<0.05). Western Blot showed that p-p38MAPK expression increased after intervention with 100, 160, 200 μg/ml artemisia annua pollen for 24 h. SB203580 could inhibit the decreasing expression of Occludin caused by artemisinin pollen (mRNA expression was 1.255±0.179 compared with 0.631±0.109, P<0.05), but had no effect on Claudin-1 protein expression. Conclusion:Pollen from artemisia annua may activate p38MAPK signaling pathway and destroy the close connection of HNEpC.

Objective:Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence.Methods:Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS.Results:A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ 2=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ 2=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ 2=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ 2=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ 2=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ 2=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ 2=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions:For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.

Objective:Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence.Methods:Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS.Results:A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ 2=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ 2=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ 2=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ 2=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ 2=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ 2=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ 2=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions:For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.

By removing a part of the structure, the tooth preparation provides restorative space, bonding surface, and finish line for various restorations on abutment. Preparation technique plays critical role in achieving the optimal result of tooth preparation. With successful application of microscope in endodontics for >30 years, there is a full expectation of microscopic dentistry. However, as relatively little progress has been made in the application of microscopic dentistry in prosthodontics, the following assumptions have been proposed: Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision? Is there a more accurate preparation technology intended for the microscope? To obtain long-term stable therapeutic effects, is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision? Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation. This article attempts to illustrate the concept, core elements, and indications of microscopic minimally invasive tooth preparation, physiological basis of dental pulp, periodontium and functions involved in tool preparation, position ergonomics and visual basis for dentists, comparison of tooth preparation by naked eyes and a microscope, and comparison of different designs of microscopic minimally invasive tooth preparation techniques. Furthermore, a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided.