This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective:To explore the effect of staged rehabilitation nursing in patients undergoing arthroscopic rotator cuff repair.Methods:From January 2021 to December 2022, convenience sampling was used to select 73 patients who underwent arthroscopic rotator cuff repair in the Department of Hand Surgery at Affiliated Hospital of Nantong University as participants. According to the random number table method, patients were divided into a control group ( n=36) and an observation group ( n=37). Control group received routine rehabilitation nursing, while observation group received staged rehabilitation nursing. The University of California, Los Angeles (UCLA) Shoulder Rating Scale score, American Shoulder and Elbow Surgeons (ASES) Rating Scale score, Constant-Murley Shoulder Scale score, and complications during rehabilitation were compared between two groups of patients before and six months after intervention. Results:Six months after surgery, both groups showed an increase in UCLA scores and ASES scores compared to before the intervention ( P<0.05), and the scores of observation group were higher than those of control group, with statistical differences ( P<0.05). Six months after surgery, the Constant-Murley Shoulder Scale scores for daily life and shoulder range of motion in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05). During the rehabilitation period, the incidence of complications in observation group was lower than that in control group with a statistical difference ( P<0.05) . Conclusions:Staged rehabilitation nursing in patients undergoing arthroscopic rotator cuff repair shows significant effects and can effectively promote patient recovery.

Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. Autophagy is a membrane driven process and tightly regulated by membrane-associated proteins. Here, we summarized membrane lipid composition, and membrane-associated proteins relevant to autophagy from a spatiotemporal perspective. In particular, we focused on three important membrane remodeling processes in autophagy, lipid transfer for phagophore elongation, membrane scission for phagophore closure, and autophagosome-lysosome membrane fusion. We discussed the significance of the discoveries in this field and possible avenues to follow for future studies. Finally, we summarized the membrane-associated biochemical techniques and assays used to study membrane properties, with a discussion of their applications in autophagy.

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.

Objective To investigate the drug resistance situation and Staphylococcal cassette chromosome mec(SCCmec) genotypes of methicillin resistant Staphylococcus aureus (M RSA ) strains isolated from Shang-hai Putuo District People′s Hospital in order to provide a theoretical basis for predicting the trend of drug re-sistant bacterial strains and clinical treatment and prevention of MRSA .Methods Three hundreds and eighty clinically isolated MRSA strains in this hospital were collected from January 2012 to December 2016 .The in vitro drug susceptibility test was performed by adopting the broth microdilution method .The SCCmec geno-types were examined by adopting the multiplex polymerase chain reaction .Results All strains were sensitive to linezolid and vancomycin ,the sensitivity rate was 100 .0％ ;the resistance rates to rifampicin and cotrimox-azole were lower ,which were 5 .0％ and 7 .6％ respectively ;but the strains were highly resistant to erythromy-cin ,levofloxacin and tetracycline ,with the resistance rate of 100 .0％ ,94 .2％ ,93 .4％ and 90 .0％ .The resist-ance rate to penicillin was 100 .0％ .Among 380 strains of MRSA ,there were 281 strains(73 .9％ ) of SCCmecⅡ ,59 strains (15 .5％ ) of SCCmecⅢand 5 strains (1 .3％ ) of SCCmecⅣa ,other 35 strains(9 .2％ ) of MRSA could not be classified .Conclusion M RSA strains isolated in the Shanghai Putuo District People′s Hospital are mainly the type SCCmecⅡ ,w hich has the multi-drug resistant characteristics ,and the drug resistance spec-trum of different SCCmec genotypes is different .

BACKGROUND: Studies have shown that osteoporosis often leads to a failure in pedicle screw fixation. Considering that the use of ordinary pedicle screw fixation cannot achieve a strong and stable fixation of the osteoporotic vertebra,special measures to strengthen the internal fixation is indispensable.OBJECTIVE: To evaluate the effect of bone cement augmentation combined with expandable pedicle screw fixation on the fixation strength of osteoporotic thoracolumbar vertebrae.METHODS: Twenty osteoporotic thoracolumbar vertebral specimens were randomly divided into four groups: conventional pedicle screw group implanted with normal pedicle screw, and the other three groups implanted with expandable pedicle screw. Bone cement augmentation with polymethylmethacrylate (PMMA) and calcium sulfate was done in the PMMA group and calcium sulfate group, respectively, followed by expandable pedicle screw implantation. No bone cement was used in the expandable pedicle screw group. The maximum axial pull-out strength and yield energy absorption value of the unilateral pedicle were detected, and the maximum removal torque of the contralateral pedicle was determined. Bone cement leakage after augmentation was observed.RESULTS AND CONCLUSION: Compared with the conventional pedicle screw group, the other three groups showed a significant increase in the maximum pull-out strength, maximum removal torque and yield energy absorption values (P < 0.05). Moreover, these parameters were significantly higher in the PMMA and calcium sulfate groups than the expandable pedicle screw group and conventional pedicle screw group (P < 0.05), but there was no significant difference between the PMMA and calcium sulfate groups (P > 0.05). No leakage of bone cement was found in all the groups. To conclude, the combined use of expandable pedicle screw and can significantly enhance the stability of the osteoporotic thoracolumbar vertebrae, and the PMMA and calcium sulfate cements have similar effects.

Aim To explore the behavior and CBS /H2 S levels of hippocampus in post traumatic stress dis-order (PTSD)rats and study the effect of exogenous H2 S on PTSD rats.Methods Single prolonged stress paradigm was adopted to prepare PTSD animal model. Morris water maze test was adopted to test space learn-ing and memory ability.CBS /H2 S content in hippo-campus tissue sample was measured using Western blot and methylene blue method.In vivo extracellular single unit recording was used to examine the frequency of spontaneous discharges of hippocampus neurons.Re-sults ① Escape latency increased and quadrant time (%)and platform crossing times decreased in Morris water maze test of PTSD group compared with normal group(P <0.01 ).CBS /H2 S level in hippocampus tis-sue of PTSD group also decreased compared with nor-mal group (P <0.01 ,P <0.05 ).② Escape latency decreased and quadrant time(%)and platform cross-ing times increased in Morris water maze test of NaHS+PTSD group compared with PTSD group(P <0.01 ).③ L-cysteine increased the frequency of spontaneous discharges of hippocampus neurons(P < 0.01 ).Con-clusions Learning and memory ability decrease in PTSD model rats owing to the inhibition of CBS /H2 S content in hippocampus tissue.The mechanism of be-havior improvement of H2 S on PTSD model rat is possi-bly related to the excitation of H2 S on frequency of spontaneous discharges of hippocampus neurons.

Objective To investigate the impact of hepatectomy combined with splenectomy on hepatitis B virus (HBV) reactivation in patients with hepatocellular carcinoma (HCC) ≤5 cm and with hypersplenism.Methods This is a retrospective case-control study on 167 patients with HCC ≤5 cm and with hypersplenism who underwent hepatectomy combined with splenectomy at the Shengli Oilfield Central Hospital between May 2008 and June 2015.64 patients underwent hepatectomy combined with splenectomy,and 103 patients hepatectomy alone.The patients were assigned to the hepatectomy combined with splenectomy group (the combined group,n =61) or the hepatectomy alone group (the control group,n =61) using propensity score matching (PSM).Logistic regression was used to evaluate the relative clinical factors associated with HBV reactivation.The stratified Chi-squared test was utilized to determine the impact of the surgical procedure and preoperative anti-viral therapy on postoperative hepatitis B virus reactivation of these patients.Results The serum PLT level,Child-Pugh grading,tumor diameter and surgical procedures were shown to be independent risk factors associated with postoperative HBV reactivation (P ＜ 0.05).To study the impact of preoperative anti-viral therapy on postoperative HBV reactivation:-the incidence of HBV reactivation was higher in the control group than in the combined group (19.7％ vs.6.6％,P ＜ 0.05).In the combined group,there was no significant difference between patients who received anti-viral therapy and those who were treatment-naive (5.3％ vs.7.1％,P ＞0.05).In the control group,a higher incidence of HBV reactivation was found in patients with treatment-na(i)ve than in patients who received anti-viral therapy (26.1 ％ vs.0,P ＜ 0.05).For the patients who received anti-viral therapy,there was no significant difference between the combined group and the control group (5.3％ vs.0,P ＞ 0.05).In patients with treatment-na(i)ve,a higher incidence of HBV reactivation was observed in the control group than the combined group (26.1％ vs.7.1％,P ＜ 0.05).Conclusions In patients who were not treated with antiviral therapy,hepatectomy combined with splenectomy decreased the incidence of postoperative HBV reactivation in patient with HCC ≤5 cm and with hypersplenism.For the patients who received preoperative anti-viral therapy,the incidence of postoperative HBV reactivation was not decreased with hepatectomy combined with splenectomy.