Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.

Objective:To explore the potential pathogenesis of exosome-mediated polymyositis/dermatomyositis (PM/DM) through multi-omics combined with bioinformatic analysis approach and to identify potential new targets for the diagnosis and treatment of PM/DM.Methods:Collect serum exosome samples from PM/DM patients and healthy individuals who underwent physical examination in Wuxi Second People′s Hospital from January 2021 to June 2023. HiSeq high-throughput sequencing technology and iTRAQ quantitative proteomics techniques were used to perform a sequencing analysis of miRNA and protein components in serum exosomes from patients with PM/DM and healthy control. R language was adapted to conduct the limma differential analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA) functional analysis, and immunological correlation analysis. Based on these analysis, we identified core genes and established a miRNA-target gene-transcription factor co-expression molecular network. Subsequently, we employed quantitative real-time PCR (qRT-PCR) to experimentally validate the core genes. Data analysis was performed using t-test statistical analysis and receiver operating characteristic (ROC) curves were plotted to evaluate the test efficacy of the core genes. Results:Initially, 42 up-regulated differential proteins and 61 DEP down-regulated differential proteins, as well as 22 up-regulated differential miRNAs and 19 down-regulated miRNAs were screened, and 7 core genes, 13 associated differential miRNAs, and 4 transcription factors were finally identified. Based on the functional analysis we concluded that the core genes CTSG, MPO, H1-5 involved in the formation of neutrophil extracellular trap network, NF-κB pathway and other inflammation-related pathways might play an important role in exosome-mediated PM/DM pathogenesis. Immune cells such as mast cells, immature dendritic cells, natural killer cells, regulatory T cells, and helper T cells 2 were expressed to a higher extent in the disease. In the t-test, MPO [(1.08 ±0.47) vs. (2.05 ±0.62), t=-3.50, P=0.004], CTSG [(1.11 ±0.51 ) vs. (2.27 ±1.10 ), t=-2.72, P=0.022], and H1-5 [(1.03 ±0.25) vs. (1.81 ±0.73), t=-2.89, P=0.019] showed statistically significant differences. In the ROC curve analysis, MPO[AUC(95% CI): 0.92(0.78, 1)], CTSG [AUC(95% CI): 0.81(0.59, 1)], and H1-5 (AUC (95% CI)= 0.84(0.64, 1)] indicated that the three core genes had good accuracy. Conclusion:We identified the key differential molecules in serum exosomes of patients with PM/DM, and constructed a regulatory network of miRNA-target gene-transcription factor, and determined that the pathogenic mechanism of PM/DM was mediated by serum exosomes was mediated through the formation of neutrophil extracellular trapping nets and the NF-κB pathway. CTSG, MPO, and H1-5 are the core genes in the these pathways, and their related miRNAs and transcription factors have been identified, which may become potential targets and biomarkers for the diagnosis and treatment of PM/DM.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective:To investigate the changes of skeletal muscle-derived microparticles (SKMPs) and their scaving proteins lactadherin in peripheral blood of patients with perihip fractures and their effects on blood coagulation. It provides a theoretical basis for clinical evaluation of hypercoagulability in patients with perioperative hip fractures.Methods:A total of 44 patients (72.87±13.9 years old) with perihip fractures from October 2020 to January 2021 were included in the fracture group, and 40 healthy people were included in the group without fracture. Activated clotting time (ACT) in fracture group and control group was measured by coagulation and platelet function analyzer. The level of SKMPs in peripheral venous blood was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of MPs scaving proteins lactadherin in peripheral blood of fracture group and control group.Results:A total of 44 patients with perihip fractures were included. There were 33 (75%) femoral neck fractures and 11 (25%) intertrochanteric fractures. SKMPs concentration in peripheral blood of perihip fracture group 175.73/μl; postoperative fracture group 124.28/μl; Normal control group 90.69/μl. ACT was (377.5±76.2) s in the perihip fracture group, (498.1±97.1) s in the post-fracture group, and (505.7±44.0) s in the control group. Correlation analysis showed that there was a linear relationship between SKMPs count and ACT value in fracture patients ( r=-0.52, P<0.001). There was no significant correlation between SKMPs concentration and ACT value in peripheral venous blood of the post-fracture group ( P>0.05); Lactadherin protein concentration in perihip fracture group: 2 779.61 pg/ml; Fracture postoperative group 1 985.38 pg/ml; Normal control group 1 651.19 pg/ml. There is a positive correlation between Lactadherin concentration and SKMPs concentration with a correlation coefficient of 0.70. Conclusion:SKMPs plays a role in the hypercoagulability of patients with perihip fractures. Decompensation of lactadherin protein may be one of the causes of perioperative hypercoagulation in patients with hip fractures.

Ten novel podophyllotoxin derivatives (IIIa-IIIi and IV) were synthesized by three-step reactions using podophyllotoxin and N-benzyloxycarbonyl glycine-L-proline as raw material. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and MS. MTT method was used to test anti-tumor activity of the target compounds on HepG2, THP-1, HeLa and MCF-7 cells. The results showed that all the target compounds had inhibitory activity against HepG2, THP-1, HeLa and MCF-7 cells, and the inhibitory activity of IIIa on HepG2 cells was the most prominent with an IC50 value of 0.58 nmol/L. The binding mode of compound IIIa and FAPα was studied by molecular docking. Compound IIIa could bind to multiple sites of FAPα enzyme.

Objective:To investigate the efficacy of enhanced recovery after surgery(ERAS)combined with laparoscopy for the treatment of colorectal cancer in the elderly and its effects on proinflammatory factors and immune responses.Methods:A total of 158 elderly patients with colorectal cancer treated with surgery were retrospectively analyzed.According to different treatment methods, they were divided into the control group(76 cases)and the study group(82 cases). The control group received traditional open surgery and routine perioperative care.The study group received laparoscopic radical resection of colorectal cancer plus perioperative ERAS.Surgery parameters, complications, postoperative immune function and proinflammatory factor levels were compared between the two groups.Results:The operation duration of the study group was significantly longer than that of the control group[(128.5±33.7)min vs.(117.4±28.7)min, t=2.220, P=0.028], whereas the intraoperative blood loss[(100.8±20.5)ml vs.(250.7±62.3)ml, t=20.621, P<0.01]and the incision length[(4.5±1.2)cm vs.(17.5±3.0)cm, t=36.243, P<0.01]were significantly less than those in the control group.The time to first flatus[(2.0±0.9)d vs.(3.8±1.8)d, t=8.037, P<0.01], time to first defecation[(2.8±0.8)d vs.(4.5±1.1)d, t=11.167, P<0.01], time to first ambulation[(1.2±0.2)d vs.(3.8±1.3)d, t=17.888, P<0.01]and hospitalization length[(7.1±0.2)d vs.(11.4±2.2)d, t=17.625, P<0.01]were also significantly shorter than those in the control group.The incidences of surgical site infections(2.4% vs.10.5%, χ2=4.351, P=0.037), abdominal distension(7.3% vs.19.7%, χ2=5.279, P=0.023)and intestinal obstruction(9.8% vs.22.4%, χ2=4.711, P=0.030)in the study group were significantly lower than those in the control group.The levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α in the study group were significantly lower than those in the control group at 1 d, 3 d and 7 d after surgery( t= 9.612, 7.300, 5.446, 8.762, 12.138, 15.370, 10.186, 10.432, 13.512, respectively, all P<0.05). The levels of CD3 + , CD4 + and CD4 + /CD8 + in the study group were significantly higher than those in the control group at 1 d, 3 d and 7 d after surgery( t= 2.128, 2.957, 2.313, 2.914, 2.937, 2.809, 5.089, 5.623, 5.409, respectively, P<0.05 for all), and the levels of CD8 + were significantly lower than those of the control group( t= 2.008, 2.580, 4.902, all P<0.05). Conclusions:Laparoscopy combined with ERAS for the treatment of colorectal cancer in the elderly can reduce surgical injury and complications and mitigate inflammatory responses with little impact on immune responses.

Objective:To discuss the efficacy and safety of ultrasound-guided rectus sheath block (RSB) combined with subcostal transversus abdominis plane block(TAPB) in peritoneal dialysis catheter implantation in patients with end-stage renal disease.Methods:A total of sixty patients (scheduled for elective peritoneal dialysis catheter placement from June 2018 to March 2019 in Wuhan First Hospital were randomly divided into two groups: local anesthesia group(group LA, 30 patients) and ultrasound-guided RSB combined with subcostal TAPB (group NB, 30 patients). Group LA: local infiltration anesthesia was performed with 1% lidocaine and 0.5% ropivacaine 20ml; group NB: RSB, 1% lidocaine and 0.5% ropivacaine 15 ml were injected into the lateral rectus sheath, and TAPB, 1% lidocaine and 0.5% ropivacaine 20 ml were injected into the transversus abdominis plane. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at the point of entering the operating room (T 0), after anaesthesia (T 1), at the beginning of operation (T 2), twenty minutes after the beginning of operation (T 3), and at the end of the operation (T 4). The duration of operation, the times of additional local anesthetia during the surgery, the score of visual analogue scale (VAS) during and 24 h after the surgery, the rate of alteration to general anesthesia and the occurrence of adverse reactions were recorded. Results:In group LA, compared with T 0, MAP and HR at T 2 and T 3 increased significantly: (93.1 ± 9.7), (99.8 ± 11.6) times/min vs. (78.4 ± 10.5) times/min and (105.1 ± 13.7), (110.5 ± 14.4) mmHg (1 mmHg = 0.133 kPa) vs. (92.1 ± 12.8) mmHg, P<0.05. In group NB, there were no differences among T 0-T 4. At T 2 and T 3, MAP and HR in group LA were higher than those in group NB ( P<0.05). Compared with that in group LA, the duration of operation time decreased significantly in group NB ( P<0.05). The times of additional local anesthetia during the surgery in group LA were more than those in group NB ( P<0.05). Compared with those in group LA, the VAS scores during and 24 h after the surgery in group NB were significantly lower: (3.25 ± 0.65) scores vs. (5.85 ± 0.76) scores, (1.46 ± 0.57) scores vs. (2.37 ± 0.45) scores, P<0.05. There were no significant differences in the rate of alteration to general anesthesia between the two groups: 3.33% (1/30) vs. 0, P>0.05. There was no adverse reaction in these two groups. Conclusions:Ultrasound-guided rectus sheath block combined with subcostal transversus abdominis plane block is safe and effective in peritoneal dialysis catheter implantation. The effect of intraoperative anesthesia is definite, with little influence on hemodynamics. The postoperative analgesia effect is good, without obvious anaesthesia-related adverse events.

Objective To investigate the effects of continuous positive airway pressure (CPAP) on sleep status,neuropsychological characteristics in patients with stroke combined with obstructive sleep apnea syndrome (OSAHS).Methods Fifty-four patients hospitalized with stroke in Tianjin Medical University General Hospital from May 2014 to January 2016,who were with snoring and met the OSAHS diagnostic criteria,were randomly divided into CPAP combined with drug treatment group (25 cases) and drug treatment alone group (29 cases).The sleep structure and respiratory parameters were evaluated by polysomnography,and the changes of the patients' sleep status was assessed by Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI).The changes of neurocognitive function were assessed by Montreal Cognitive Assessment (MoCA),Digital Span Test (DST) and Hopkins Verbal Learning Testrevised (HVLT),and Patient Health Questionnaire-9 (PHQ9) was used to evaluate the depression mood changes.The changes of sleep status,cognitive function and mood in the CPAP combined with drug treatment group were compared before and three months after CPAP combined with drug treatment,and with the drug treatment alone group.Results Because five cases were dropped off,there were 20 patients in the CPAP combined with drug treatment group and 29 patients in the drug treatment alone group who completed the study.After three months of CPAP combined with drug treatment,the respiratory parameters apnea hypopnea index (AHI) in the CPAP combined with drug treatment group (29.32 ± 16.57) was significantly lower than that before treatment (41.66 ± 21.84;t =3.926,P =0.001),and the minimum blood oxygen saturation (LSaO2;82.11％ ± 5.66％) was significantly higher than that before treatment (76.11％ ± 8.90％;t=-5.054,P=0.000).However,the sleep structure parameters did not show statistically significant changes compared with those before treatment.The ESS,PSQI and PHQ9 scores in the CPAP combined with drug treatment group (4.53 ± 3.86,3.00 ± 2.45,0.00 (0.00,2.00)) were significantly decreased compared with those before treatment (10.58 ± 7.82,7.53 ± 2.87,3.00 (1.00,9.00);t =-3.883,P =0.001;t =-6.522,P =0.000;Z =-3.549,P =0.000),whereas MoCA,HVLT (total scores,recall and recognition) and DST 1,2 scores in the CPAP combined with drug treatment group (23.37 ± 4.75,22.32 ± 6.90,7.47 ± 3.82,7.84 ± 2.59,5.32 ± 2.81) were increased compared with those before treatment (22.16±4.94,19.16 ±7.66,6.68 ±3.74,7.32 ±2.67,5.00 ±3.00;t=-2.773,P=0.013;t=-6.857,P=0.000;t=-2.704,P=0.015;t=-2.249,P=0.037;t=-2.882,P =0.010).The ESS,PSQI and PHQ9 scores were significantly reduced in the CPAP combined with drug treatment group compared with the drug treatment alone group (8.76 ± 6.92,7.59 ± 5.49,5.00 (2.50,9.50);t=-2.711,P=0.009;t=-3.941,P=0.000;Z=-4.555,P=0.000),whereas the DST1 score was significantly increased compared with the drug treatment alone group (6.45 ± 1.43;t =2.144,P =0.042).Conclusions Three-month CPAP combined with drugs mainly improved the daytime sleepiness and depression of patients with stroke combined with OSAHS.Cognition especially in attention was significantly improved,and the degree of low ventilation and hypoxia was alleviated,whereas there was no significant change in sleep structure disorder.

Objective To observe the effect of proximal needling at Tianzhu (BL10) plus electroacupuncture at the Balance Zone on the lower-limb motor function and walking function in cerebral stroke patients.Method A hundred cerebral stroke patients were randomized into a rehabilitation group and a proximal needling group. The rehabilitation group was intervened by balance training and conventional rehabilitation exercises; the proximal needling group was intervened by proximal needling at Tianzhu plus electroacupuncture at the Balance Zone in addition to the treatment given to the rehabilitation group. The interventions weregiven once a day, 5 times a week, successively for 4 weeks. Prior to the intervention and after 4-week treatment, the lower-limb motor function and walking function were estimated by using lower-extremity Fugl-Meyer Assessment (FMA), time taken for 10-meter walk, and Holden's Functional Ambulation Classification (FAC).Result After 4-week treatment, the FMA, 10-meter walk time and FAC were significantly enhanced in both groups compared to the indexes prior to the treatment (P<0.01); the FMA, 10-meter walk time and FAC in the proximal needling group were significantly superior to those in the rehabilitation group (P<0.05).Conclusion In addition to conventional rehabilitation and acupuncture, proximal needling at Tianzhuplus electroacupuncture at the Balance Zone can increasethe lower-limb motor function score and promote the activities of daily life in cerebral stroke patients; it can also strengthen the security in walking and keep the patients from falling down.

Objective To discuss the effect of Dickkopf-1 (DKK-1) on Wnt singal pathway during the differentiation of osteoblast in vitro.Methods The osteoblasts were obtained from the new rats and cultured in vitro.The 3 passages were divided into control group and DKK-1 group.The cells were cultured in DKK-1 and normal saline for morphogical detection,ALP activity detection and osteoblasts stained at 1 st,6th,12th,21st day.The Wnt was detected by RT-PCR.Results After cultured by the DKK-1 in vitro,the ALP and mineralization of osterblasts staining were prlonged with culture time.Compared with control group,the expression of Wnt was significantly reduced at the 21st day after induction (t =0.278,P ＜ 0.05).Conclusion DKK-1 can regulate the expression of Wnt during osteoblast differentiation,suggests that Wnt may be involved in osteoblast differentiation and can affect bone remodeling process.