OBJECTIVE: To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. METHODS: RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. RESULTS: 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. CONCLUSION 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism* ; Arthritis, Rheumatoid/metabolism* ; Animals ; Cell Movement/drug effects* ; Humans ; Catechols/therapeutic use* ; Fibroblasts/drug effects* ; Mice ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/cytology* ; Cells, Cultured ; Male ; Arthritis, Experimental ; Anti-Inflammatory Agents/pharmacology* ; NF-KappaB Inhibitor alpha ; Inflammation

Objective:To design a fully integrated multi-channel implantable brain-computer interface electrical stimulation system.Methods:The human-computer interaction interface of the upper computer was set by users, and the data was packaged via a self-built protocol. When parameters were transmitted to the field programmable gate array (FPGA) chip through the Bluetooth module, the stimulation chip was controlled after the parameter analysis was completed. Eventually the user-set current stimulation was output. To verify the system feasibility, the accuracy of the single-channel stimulation waveform, the multi-channel output capability, and the adjustable range of the parameter were tested separately.Results:It realized 16 channels of time-sharing differential stimulation current output, the output stimulation current waveform was dual-phase equal-width pulse, the amplitude ranged within 4~1 000 μA, the pulse single-phase width range was 10~1 000 μs, the cycle time was 1~1 000 ms, thus the current parameters could be accurately adjusted.Conclusions:A fully integrated multi-channel implantable brain-computer interface electrical stimulation system was completed.

Objective:To investigate the effectiveness of antibiotics in preventing surgical site infection (SSI) after hepatectomy.Methods:The clinical data of patients who underwent hepatic resection at the Department of Biliary and Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, from Jan 2019 to Dec 2021, were retrospectively analyzed.Results:A total of 509 patients were included in the study. There was no statistically significant difference in the incidence of SSI in the different prophylactic treatment time groups ( P>0.05). Univariate analysis revealed bile leakage, extent of hepatic resection, surgical procedure, level of anesthesia, and duration of surgery as potential risk factors for SSI after hepatic resection ( P<0.05); Multivariate analysis showed that bile leakage, extensive hepatic resection, open surgical approach, grade 3-4 anesthesia level, and operative time longer than 300 minutes might be independent risk factors affecting SSI after hepatectomy ( P<0.05). Conclusion:Prolonging antibiotic prophylaxis for SSI after hepatectomy may be unnecessary.

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

Objective     To explore the timing and safety of limited-period lung cancer surgery in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods     Clinical data of of patients infected with COVID-19 undergoing lung cancer surgery (an observation group) in the Department of Thoracic Surgery of Guangdong Provincial People's Hospital, the Department of Thoracic Surgery of General Hospital of Southern Theater Command of PLA, and the Department of Cardiothoracic Surgery of the First Affiliated Hospital of Guangdong Pharmaceutical University from December 2022 to January 2023 were retrospectively analyzed and compared with patients who underwent surgery during the same period but were not infected with COVID-19 (a control group), to explore the impact of COVID-19 infection on lung cancer surgery. Results     We finally included 110 patients with 73 patients in the observation group (28 males and 45 females at age of 52.62±12.80 years) and 37 patients in the control group (22 males and 15 females at age of 56.84±11.14 years). The average operation time of the observation group was longer than that of the control group, and the incidence of anhelation was higher than that of the control group (P<0.05). There were no statistcal differences in blood loss, length of hospital stay, moderate or above fever rate, degree of cough and chest pain, or blood routine between the two groups. Conclusion    It is safe and feasible to perform lung cancer surgery early after recovery for COVID-19 patients with lung cancer.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with a very poor prognosis.In order to guide better clinical management of ICC patients,the American Joint Committee on Cancer (AJCC) cancer staging manual (7th edition) have established a unique TNM staging scheme for separating ICC from hepatocellular carcinoma (HCC) for the first time,and reflected a difference between risk factor of ICC and HCC.This TNM staging system for ICC has been most recently updated by the AJCC cancer staging manual (8th edition),in which T staging has been redefined without gross features,and lymph node metastasis (N1) in N staging has been grouped as stage Ⅲ B,but not stage Ⅳ as required by the 7th edition of AJCC cancer staging manual.In addition,region lymphatic and distant metastases have been clearly redefined by the AJCC cancer staging manual (8th edition) that also requires recovering at least 6 lymph nodes for the N staging scheme.The apparent advantages of the AJCC cancer staging manual (8th edition) for ICC pathologic staging may better stratify the prognosis of ICC patients and provide an improved guidance in clinical practice.

Objective To investigate the minimum local analgesic concentration(MLAC)of epidural hydromorphone combined with bupivacaine for analgesia during the first stage of labor by establishing clinical model.Methods Sixty four labouring parturi-ents at 3-7 cm cervical dilation who requested epidural analgesia were allocated to one of two groups.After a lumbar epidural cath-eter was placed,study participants received 15 mL bupivacaine(n=30),bupivacaine with hydromorphone 200 μg(n=30).The con-centration of bupivacaine was determined by the response of the previous patient using 0 - 100 mm visual analog pain scores, with≤30 mm within 30 min defined as effective.Results Four women were excluded,leaving 30 patients in each of the two groups for analysis.The MLAC of bupivacaine alone was 0.103%(95% CI :0.094%-0.113%).The addition of hydromorphone at doses of 200 μg resulted in significant reduction(P <0.05)in the MLAC of bupivacaine to 0.044%(95% CI :0.034%-0.053%),the difference was significant (P <0.05).There was no significant difference in Bromage scores,HR,BP,FHR,UC and adverse reac-tion (P >0.05).Conclusion The study showed a significant reduction in the MLAC of bupivacaine by hydromorphone.Hydromor-phone could be safely used in epidural analgesia for labor.

objective To evaluate the clinical effect of touqing capsule associated with Fengchi on the vertebral artery type of cervical spondylosis(CSA)in the attack stage.Methods A total of 100 patients with CSA, according to the doctor order, were randomly divided into a control group and a treatment group respectively, with 50 patients in each. The control group was treated with acupuncture therapy, the treatment group was additionally treated with Touqingcapsule on the basis of the control group, and both groups were treated for 20 days. The hemodynamics was detected by transcranial doppler, the change of TCM syndrome integral was observed before and after the treatment, and the clinical efficacy was evaluated.Results After treatment, the treatment group dizziness (1.10 ± 0.33 vs. 2.01 ± 0.26,t=14.909), neck shoulder ache (0.87 ± 0.16 vs. 1.92 ± 0.69,t=10.266), numbness (0.95 ± 0.14)vs. 1.87 ± 0.16,t=29.844), the total integral (2.16 ± 0.75 vs.3.89 ± 1.14,t=8.756) integral were significantly lower than the control group(P<0.01).Treatment group RVA (40.03 ± 5.89 cm/svs. 34.26 ± 6.26 cm/s,t=4.628), the LVA (42.14 ± 5.42 cm/svs.33.89 ± 6.08 cm/s,t=6.985) rise and PI (0.79 ± 0.14 vs.1.04 ± 0.19,t=7.312) reduction were significantly better than those of the control group (P<0.01). The total effective rate in the treatment group was significantly better than the control group (91.7%(44/48)vs. 74.5%(35/47),χ2=3.863, P=3.863).Conclusion Touqing Capsule associated with Fengchi is effective for CSA. Its functional mechanism is correlated with improvement of haemodynamics of vertebral-basilar artery of the CSA patients.

Anterior approach refers to a method of hepatectomy which is first to resect the hepatic parenchyma and then to free the liver; hanging maneuver refers to placing a tape before the inferior vena cava for hanging the liver during hepatectomy.In October 2011,anatomical trisectionectomy was performed on a 54-year-old male patient with large hepatocellular carcinoma in the left medical lobe and right lobe with anterior approach and hanging maneuver.The diameter of the tumor was 16 cm,and was in the ⅢA/T3NOM0 stage.The indocyanine green retention at fifteen minutes was 5.4％,and the ratio of hepatic left lateral lobe volume over the standard total liver volume was 44％.The left bile duct was slightly dilated because of the compress of the tumor.The operation started with the isolation and dissection of the inflow vessels,including the right hepatic artery,the right portal vein,the middle hepatic artery,the portal vein branches of left internal lobe.The hepatic parenchyma transection was performed along the fight side of the falciform ligament.A tape was passed between the anterior surface of inferior vena cava and liver,and the liver was suspended during the transection.The left bile duct was cut at the right side of round ligament,and then the middle hepatic vein and the right hepatic vein were resected.The ligaments around the liver were dissected and the right hepatic lobe was removed.Finally,the end-toend anastomosis between the left hepatic duct and the common hepatic duct was performed.The operation lasted for 4 hours and the intra-operative blood loss was 350 mL.The patient was recovered well.At the end of 4 months after surgery,magnetic resonance cholangiopancreatography showed that the anastomosis of the bile duct was unobstructed,and there was no recurrence of tumor inside the liver.

Objective To study the toxicity and efficacy of induction chemotherapy followed by concurrent cisplatin chemotherapy and three dimensional conformal radiotherapy (3DCRT) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC). Methods Totally 76 patients with LA-NSCLC received two cycles induction chemotherapy followed by 3DCRT with a median dose of 68 Gy (64 to 74 Gy).During the 3DCRT, cisplatin (25 mg/m2, weekly) was given intravenously for 6-7 times. Results The CR rate, PR rate and overall response rate of induction chemotherapy were 3% ,42% and 45%. After the concurrent chemoradiation, the corresponding figures were 10%, 62% and 72%. The median survival time (MST) and median progression-free survival (PFS) of all patients were 16.6 months and 10.3 months. The 1-, 2- and 3-year overall survival (OS) and PFS rates were 67% , 35% , 21% and 42% , 15%, 6%. Of patients with stage ⅢA and stage ⅢB disease,the MST were 19.7 months and 15.6 months, the PFS were 10.8 months and 9.4 months. The major treatment-related toxicities included radiation esophagitis, radiation pneumonitis, nausea ( or vomiting) and leukopenia. The major pattern of treatment failure was distant metastasis. Forty-five patients (59%) experienced the local recurrence or/and distant metastasis, including 4 (9%) with in-field failure, 38 (84%) distant metastasis and 3 (7%) malignant pleural effusion. Conclusions Induction chemotherapy followed by concurrent weekly cisplatin and 3DCRT for inoperable locally advanced NSCLC results in encouraging outcomes and acceptable tolerance.