Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Objective:To study the characteristics and management of peripancreatic effusion in chronic pancreatitis.Methods:Data of 32 patients with chronic pancreatitis and 141 acute pancreatitis admitted to the First Affiliated Hospital of Guangxi Medical University from January 2018 to December 2019 were collected. According to the Atlanta classification, the peripancreatic effusion was divided into four categories: acute peripancreatic fluid collection (APFC), acute necrotic collection(ANC), pancreatic pseudocyst (PPC) and walled-off necrosis (WON). The general information, clinical manifestations, medical history, laboratory examination indicators and treatment of the four types of patients were recorded and analyzed.Results:Among the 32 patients with chronic pancreatitis complicated with peripancreatic effusion, 27 patients (84.4%) were diagnosed as having PPC, 3 patients (9.4%) WON and 2 (6.2%) APFC. No chronic pancreatitis with ANC was found. The incidence of PPC was higher in patients with chronic pancreatitis than those with acute pancreatitis [84.4% (27/32) VS 31.2% (44/141), P<0.01], and the APFC was lower [6.2% (2/32) VS 24.8% (35/141), P=0.021]. The incidence of ANC was also lower [0.0% (0/32) VS 36.9% (52/141), P<0.01], and there was no significant difference in the incidence of WON [9.4% (3/32) VS 7.1% (10/141), P=0.944]. Compared with patients with peripancreatic effusion of chronic pancreatitis, acute pancreatitis showed a higher proportion of clinical manifestations: fever [19.1% (27/141) VS 3.1% (1/32)], nausea [59.6% (84/141) VS 21.9% (7/32)], vomit [56.7% (80/141) VS 21.9% (7/32)], tenderness [79.4% (112/141) VS 34.4% (11/32)], rebounding pain [42.6% (60/141) VS 0.0% (0/32)], increase of C reactive protein [95.7% (135/141) VS 40.6% (13/32)] ( P< 0.05), and the mean hospital stay was longer (13 days VS 11 days, P=0.048). Imaging examination showed that the proportion of lesions >5 cm in diameter in PPC patients with acute pancreatitis was higher than those with chronic pancreatitis [70.5% (31/44) VS 29.6% (8/27), P=0.001]. WON in chronic pancreatitis patients was limited to the pancreas [3/3 VS 1/10, P =0.014]. In terms of treatment strategies, 25 patients (78.1%) received conservative treatment in 32 chronic pancreatitis. There was no significant difference in treatment strategy between patients with acute pancreatitis and those with chronic pancreatitis. Conclusion:In the peripancreatic effusion of chronic pancreatitis, PPC is the most common. Peripancreatic effusion is mainly treated conservatively. There is no difference in treatment among different types of peripancreatic effusion in chronic pancreatitis. However, compared with chronic pancreatitis, peripancreatic effusion in acute pancreatitis may need more active intervention.

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

Objective:To investigate the relationship between Helicobacter pylori(Hp)infection and carotid atherosclerosis(CAS)in the elderly, in order to provide an empirical basis for the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly.Methods:A total of 287 patients aged 60 years and over admitted to the First Affiliated Hospital of Guangxi Medical University, who underwent the 13C-urea breath test( 13C-UBT), carotid color and two-dimensional Doppler ultrasonography from October 2015 to January 2019, were retrospectively enrolled.Patients were divided into the Hp infection group(n=137)and the non-Hp infection group(n=150). Common high-risk pathogenic factors, blood biochemical indicators, carotid intima-media thickness(IMT)and detection rate of carotid plaque were compared between the two groups. Results:Common high-risk pathogenic factors including age, gender, hypertension, diabetes, obesity, smoking, alcohol consumption, dyslipidemia, and hyperuricemia showed no significant difference between the two groups( P>0.05). The level of high-density lipoprotein cholesterol(HDL-C)was lower in the Hp infection group than in the non-Hp infection group( P<0.05). There was no difference in levels of white blood cells, neutrophils, total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), homocysteine, fasting blood glucose, creatinine or uric acid between the two groups( P>0.05). The detection rates of increased carotid IMT and carotid plaques were higher in the Hp infection group than in the non-Hp infection group(65.0% or 89 cases vs.48.7% or 73 cases, 76.6% or 105 cases vs.64.7% or 97 cases, P<0.01 and 0.05). The detection rate of carotid plaques in the Hp-infected group was higher than that in the non-Hp-infected group( P<0.05). The combined detection rate of increased carotid IMT and plaques was higher in the Hp infection group than in the non-Hp infection group(56.2% or 77cases vs.32.7% or 49 cases, P<0.01). Conclusions:Hp infection may play a role in the occurrence and progression of carotid atherosclerosis through initiating abnormal lipid metabolism.Early intervention and treatment may reduce the incidence of carotid atherosclerosis in patients with Hp infection.

BACKGROUND:The effects of advanced glycation end products (AGEs) on osteoclast-induced bone resorption is controversial and the underlying mechanisms remain unclear. Most of the studies indicate that AGEs can enhance bone resorption, while some othersshowthe opposite effects.
OBJECTIVE:To investigate the effects of AGEs on osteoclast-induced inorganicmatrixdissolution and organic componentdegradation and the underlying mechanisms.
METHODS:RAW 264.7 cels were induced to generate osteoclasts,and AGEs (50-400 μg/mL) or control-bovine serum albumin (100 μg/mL) was added since the beginning of the induction. The effect of AGEs on bone resorption was evaluated by analyzing the area of resorption pits on the Osteo Assay Surface plates and the expression of cathepsin K. Furthermore, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cels, nuclei per osteoclasts and the expression of integrinανβ3were detected.
RESULTS AND CONCLUSION:The area of resorption pits and expression of cathepsin K in AGEs groups were significantly decreased compared withthecontrol group, and this inhibiting effect became more obvious with the increase of AGEs concentration. TRAP staining also showed that number of TRAP-positivemultinucleated celsand nuclei per osteoclast were significantly reduced in an AGE dose-dependent manner. Quantitative PCR revealed that the expression of integrin ανβ3decreased significantly with the extension of AGEs incubation time. These data indicate that AGEs can exert inhibitory effects on organic and inorganicmatrixdegradation induced by osteoclasts. The underlying mechanism may be involved in the inhibitory effects of AGEs on directed differentiation and cel fusion of osteoclast precursor cels, and migration and adhension of osteoclasts.

Objective To evaluate the therapeutic effect of endoscopic management of plastic stents of post-liver transplantation anastomotic biliary stricture. Methods From January 2010 to October 2015, clinical data of patients with post-liver transplantation anastomotic biliary stricture and received endoscopic retrograde cholangiopancreatog﹣raphy and plastic stents management was collected. The technical success rate, ERCP-related complications, clinical remission rate and long-term complications were main outcome measurements to compare the efficacy and safety of different number of stents in managing post-liver transplantation anastomotic biliary stricture. Results Among the 18 patients (0.5 ~ 60.0 months) with post-liver transplantation ABSs, seven patients received less plastic stents treat﹣ment (< 3 stents), nine patients with persistent anastomotic or recurrent stricture received multiple plastic stents treatment (≥ 3 stents), two patients received multiple plastic stents treatment once suffered with post-liver trans﹣plantation ABSs. The endoscopic technical success rate was seventy-six over eighty (95.0 %). Among the seven pa﹣tients received less plastic stents treatment, one loss to follow-up, two were still under treatment, one died of acute hepatic failure, one died of septic stock, one combined with biliary fistula resulted in treatment failure, one achieved clinical remission, the clinical remission rate was one third (33.3 %). Among the eleven patients received multiple plastic stents treatment, two loss to follow-up, one was still under treatment, two received surgery because of failed treatment, six achieved clinical remission, the clinical remission rate was 75.0 % (6/8). The average diameters and stent durations of management of 1 stent, 2 stents, 3 stents, 4 stents, 5 stents, 7 stents were 8.5 F, 17.0 F, 24.0 F, 28.0 F, 36.0 F, 50.0 F. Among the six early postoperative complications, five cases occurred in less stent manage﹣ment and one occurred in MPSs management, the early postoperative complication rate was 7.5 %(6/80). No severe ERCP-related complications and procedure-related deaths. Conclusions Endoscopic management of plastic stents is safe and effective for post-liver transplantation ABSs. Providing larger biliary support, the multiple plastic stents treatment was superior to less plastic stents treatment in view of clinical remission rate, especially for refractory one. Multiple plastic stents did not increase the incidence of complications, it could be used as the first-line treatment of post-liver transplantation duct-to-duct biliary anastomosis for its safety and effectivity.

OBJECTIVEThe aim of this study was to compare the short-term outcomes for hand-assisted, laparoscopic, and open resection for rectal cancer.

METHODSThree hundred ninety patients with rectal cancer who underwent curative resection between June 2009 and June 2012 were included. Patients were classified into a hand-assisted group (HALS, n=101), a laparoscopic surgery group (LS, n=157), and an open surgery group (OS, n=132). Patient and disease characteristics, operative parameters, postoperative morbidity, pathological results and length of recovery were compared among three groups.

RESULTSThe mean operating time was (173±39) min for the HALS group, (231±61) min for the LS group, and (173±39) min for the OS group (P<0.01). Conversion rates did not differ between HALS and LS groups (2.0% vs 3.2%, P=0.708). The overall complication rates were 11.9%, 11.5%, and 19.7% in the HALS, LS and OS groups respectively (P=0.100). The specimen quality with a specimen length, distal resection margin, harvested lymph nodes, and positive lymph nodes did not differ among the three groups. Patients in the HALS and LS groups recovered significantly faster than those from the OS group.

CONCLUSIONSThis comparative study shows that HALS and LS can reproduce the equivalent short-term results of standard OS. HALS retained the minimal invasive advantages of LS, and significantly shorten the operation time.

Aged ; Female ; Humans ; Laparoscopy ; methods ; Laparotomy ; Male ; Middle Aged ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Treatment Outcome

Objective The aim of this study was to compare the short-term outcomes for hand-assisted, laparoscopic, and open resection for rectal cancer. Methods Three hundred ninety patients with rectal cancer who underwent curative resection between June 2009 and June 2012 were included. Patients were classified into a hand-assisted group (HALS, n=101), a laparoscopic surgery group (LS, n=157), and an open surgery group (OS, n=132). Patient and disease characteristics, operative parameters, postoperative morbidity, pathological results and length of recovery were compared among three groups. Results The mean operating time was (173±39) min for the HALS group, (231±61) min for the LS group, and (173 ±39) min for the OS group (P<0.01). Conversion ratesdid not differ between HALS and LS groups (2.0% vs 3.2%, P=0.708). The overall complication rates were 11.9%, 11.5%, and 19.7% in the HALS, LS and OS groups respectively (P=0.100). The specimen quality with a specimen length, distal resection margin, harvested lymph nodes, and positive lymph nodes did not differ among the three groups. Patients in the HALS and LS groups recovered significantly faster than those from the OS group. Conclusions This comparative study shows that HALS and LS can reproduce the equivalent short-term results of standard OS. HALS retained the minimal invasive advantages of LS, and significantly shorten the operation time.

Objective The aim of this study was to compare the short-term outcomes for hand-assisted, laparoscopic, and open resection for rectal cancer. Methods Three hundred ninety patients with rectal cancer who underwent curative resection between June 2009 and June 2012 were included. Patients were classified into a hand-assisted group (HALS, n=101), a laparoscopic surgery group (LS, n=157), and an open surgery group (OS, n=132). Patient and disease characteristics, operative parameters, postoperative morbidity, pathological results and length of recovery were compared among three groups. Results The mean operating time was (173±39) min for the HALS group, (231±61) min for the LS group, and (173 ±39) min for the OS group (P<0.01). Conversion ratesdid not differ between HALS and LS groups (2.0% vs 3.2%, P=0.708). The overall complication rates were 11.9%, 11.5%, and 19.7% in the HALS, LS and OS groups respectively (P=0.100). The specimen quality with a specimen length, distal resection margin, harvested lymph nodes, and positive lymph nodes did not differ among the three groups. Patients in the HALS and LS groups recovered significantly faster than those from the OS group. Conclusions This comparative study shows that HALS and LS can reproduce the equivalent short-term results of standard OS. HALS retained the minimal invasive advantages of LS, and significantly shorten the operation time.