Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

Gap junction proteins have a significant impact on the propagation of neuroinflammation after cerebral ischemia.Connexin 43(Cx43),the principal connexin in the central nervous system,typically assembles hexameric hemichannels in an oligomeric state that dock with hemichannels on adjacent cells to form gap junction channels.Ordinarily,the likelihood of cell surface hemichannels opening is minimal.However,during cerebral ischemia,the excessive activation of Cx43 hemichannels leads to the liberation of a substantial quantity of ions(Na+,Cl-,Ca2+,and K+),glutamate,aspartate,and adenosine triphosphate(ATP),thereby resulting in impairment of adjacent cells and aggravation of neuronal injury.Furthermore,the activation of Cx43 hemichannels triggers the release of inflammatory factors,which exhibits a strong association with the activation of NLRP3 inflammasome after cerebral ischemia.Hence,the modulation of Cx43 hemichannels presents a potential avenue for mitigating neuroinflammation and subsequently diminishing cerebral ischemic injury.This article focuses on the relationship between Cx43 hemichannels and NLRP3 inflammasome activation,as well as its role in cerebral ischemia,all of which provide novel insights and therapeutic approaches for managing cerebral ischemia.

Obejective　To investigate and compare the clinical efficacy of aroma massage with traditional massage in the treatment of chronic fatigue syndrome （CFS）. MethodsSeventy-two CFS patients were randomized into the aroma massage group and the traditional massage group， with 36 patients in each group. Both groups were treated with essential oil aromatherapy and massage were performed on the head， face， and abdomen stimultaneously. The aroma massage group used antifatigue oil， while the traditional massage group used placebo essential oil. The two groups were treated for 30 minutes each time， once every other day， three times a week， for a total of 4 weeks. The fatigue scale （FS-14） score， traditional Chinese medicine （TCM） syndrome score and patient satisfaction evaluation scale score before and after the treatment of the two groups were assessed to study the improvement of fatigue and other clinical symptoms of the patients as well as the changes of the TCM symptom scores， and to evaluate the clinical efficacy of the two groups. ResultsWith three drop-outs in the traditional massage group and two drop-outs in the aroma massage group， 33 cases in the traditional massage group and 34 cases in the aroma massage group were included in the outcome analysis. The FS-14 scores and TCM syndrome scores significantly decreased after treatment in both groups （P＜0.01）； compared to those in the traditional massage group （FS-14： 4.42±2.44； TCM syndrome score： 34.12±7.67）， the FS-14 score （3.06±2.37） and TCM syndrome score （28.79±5.62） in the aroma massage group were significantly lower （P＜0.05 or P＜0.01）. There was no significant difference in the satisfaction scores of the patients in the two groups after the treatment （P＞0.05）. The total effective rate of the aroma massage group was 94.12% （32/34）， which was significantly higher than 84.85% （28/33） of the traditional massage group （P＜0.05）. ConclusionBoth aromatherapy and traditional massage can improve the clinical symptoms of fatigue in CFS patients， and aromatherapy is more effective， which is easy to operate with high patient acceptance.

As the main water channel expressed in the brain,aquaporin 4(AQP4)has been implicated in the pathological process of ischemic stroke.After ischemic stroke,the expression,phosphorylation and polarity distribution of AQP4 are affected by the process of transcription and post-translational modification.The paper summarized the basic structure,physiological function,dynamic expression changes and mechanisms of AQP4 in this review,specifically discussing the role of AQP4 in cerebral edema,blood-brain barrier permeability and neuroinflammation after ischemic stroke,offering an up-to-date perspective on further effective therapeutic strategies for ischemic stroke.

Objective To explore the effects of M1 polarization of microglia on secondary damage in the thalamus after cerebral cortical infarction.Methods A focal cortical infarct model of adult male SD rats was pre-pared using eletrocoagulation and randomized into Sham and model groups at different time points 1～4 weeks after surgery.Based on the assessment of neurofunctional changes in each group of rats,immunohistochemistry was used to observe the number and morphology of NeuN,GFAP and Iba-1 positive cells in(Ventral posterior nucleus of thalamus,VPN)of the ipsilateral thalamus after distal middle cerebral artery occlusion(dMCAO).Immunofures-cence was used to detect the number and morphology of M1 microglia marker(Iba-1+/CD68+cells)and M2 microg-lia marker(Iba-1+/CD206+cells)in VPN of the ipsilateral thalamus after dMCAO.Western blot was used to detect the expression levels of IL-1β,TNF-α,IL-10 and Arg-1 in VPN of the ipsilateral thalamus after dMCAO.Results The results of immunohistochemistry showed a significant decrease in NeuN positive cells and an increase in the density of GFAP and Iba-1 in the ipsilateral VPN of rats after dMCAO when compared with Sham group(P<0.001).Compared with sham group,the protein levels of TNF α and IL-1β were elevated in the ipsilateral VPN elevated(P<0.05).In addition,the model group rats exhibited higher Bederson scores,beam-walking test and adhesive removal test scores after dMCAO compared with Sham group(P<0.05).The numbers of M1 microglia marker(Iba-1+/CD68+cells)were significantly increased when compared with M2 microglia marker(Iba-1+/CD206+cells)in ipsilateral VPN of rats after dMCAO.Conclusion M1 polarization of microglia may play an essential role in secondary damage of thalamus after cerebral cortical infarction.

Objective:To explore the influence of pancreatic stents of different lengths on the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).Methods:Data of 299 patients with biliary tract diseases who received endoscopic retrograde cholangiopancreatography (ERCP) and 5 Fr prophylactic pancreatic stents placement at the First Affiliated Hospital of Air Force Medical University from January 2013 to January 2022 were retrospectively analyzed. Patients were divided into the short-stent group (<5 cm, n=163) and the long-stent group (>5 cm, n=136). Baseline data, intraoperative procedures, and postoperative outcomes were compared between the two groups and propensity score matching (PSM) was used for complementary analysis. The primary endpoint was the incidence of PEP. The risk factors for PEP in patients with prophylactic pancreatic stents placement was explored by logistic regression analysis . Results:The overall PEP incidence was 11.0% (33/299). There was no significant difference in the PEP incidence [11.7% (19/163) VS 10.3% (14/136), χ 2=0.140, P=0.708], moderate-to-severe PEP incidence [1.8% (3/163) VS 2.2% (3/136), χ 2=0.000, P=1.000], or spontaneous stent dislodgement rate within two weeks [81.7% (103/126) VS 78.4% (87/111), χ 2=0.421, P=0.516] between the two groups. After PSM, 123 patients were included in each group, and the overall PEP incidence was 8.9% (22/246). There was no significant difference in PEP incidence [8.9% (11/123) VS 8.9% (11/123), χ 2=0.000, P=1.000], moderate-to-severe PEP incidence [0.8% (1/123) VS 1.6% (2/123), χ 2=0.000, P=1.000], or spontaneous stent dislodgement rate within two weeks [80.6% (75/93) VS 78.6% (77/98), χ 2=0.126, P=0.722] between the two groups. Logistic regression analysis showed that normal liver function ( OR=2.36, 95% CI:1.01-5.51, P=0.046) and failed bile duct cannulation ( OR=7.51, 95% CI:2.18-25.96, P=0.001) were independent risk factors for PEP in patients with biliary tract diseases who received prophylactic pancreatic stents placement. Conclusion:Longer 5 Fr pancreatic stents (>5 cm) do not further reduce the overall risk of PEP or moderate-to-severe PEP compared with 5Fr-5 cm stent. Normal liver function and failure of bile duct intubation were independent risk factors for PEP after prophylactic pancreatic stent placement in patients with biliary diseases.

Gastrointestinal tumors(GT)are characterized by both high malignancy and high mortality and have become the major diseases for prevention in the elderly.GT often present detectable changes, including bleeding and abnormal mucosal morphology.However, many technical difficulties remain in accurately monitoring the tumor itself and related abnormal lesions mentioned above, which are the key factors affecting the early detection rate of gastrointestinal tumors.In recent years, with progresses in artificial intelligence(AI)applications for digestive endoscopy image analysis, biosensors, new biomarkers and other areas, AI holds promise for the detection of bleeding, morphological and structural abnormalities of the mucosa, tumors and other major disorders.Here we review the progress of AI applications in geriatric digestive diseases affecting digestive organs and the mucosa in light of morphology and function, to provide a reference for reducing the incidence of both geriatric emergencies and GT.

Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.

Objective:To evaluate the effect of remimazolam combined with propofol for sedation in the pediatric patients undergoing outpatient root canal treatment.Methods:Seventy pediatric patients of either sex, aged 2-6 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with an expected treatment time<1 h, scheduled for elective outpatient root canal treatment, were divided into 2 groups ( n=35 each) using a random number table method: propofol group (P group) and remimazolam plus propofol group (RP group). Induction of anesthesia was as follows: propofol 1-3 mg/kg was intravenously injected until BIS value was less than 60 in group P, and remimazolam 0.2 mg/kg and propofol 1-3 mg/kg were intravenously injected until BIS value was less than 60 in group RP.Anesthesia maintenance was as follows: propofol 6-12 mg·kg -1·h -1 was intravenously infused in group P, and remimazolam 0.3 mg·kg -1·h -1 and propofol 6-12 mg·kg -1·h -1 were intravenously infused in group RP.The BIS value was maintained at 50-70 during operation.Spontaneous breathing was kept, and oxygen was inhaled through a nasal catheter with oxygen flow rate of 2-3 L/min in both groups.The amount of propofol consumed during induction and maintenance periods and the total consumption were recorded.The onset time of sedation, duration of operation, emergence time and duration of post-anesthesia care unit stay were recorded.The adverse reactions such as intraoperative respiratory depression, hypotension, bradycardia, coughing and body movement, emergence agitation and postoperative nausea and vomiting were recorded. Results:Compared with group P, the amount of propofol consumed during induction and maintenance periods and the total consumption were significantly reduced, the onset time of sedation was prolonged, the emergence time and duration of post-anesthesia care unit stay were shorted, the incidence of respiratory depression was decreased ( P<0.05), and no significant change was found in the incidence of duration of operation, hypotension, bradycardia, body movement or emergence agitation in group RP ( P>0.05). No intraoperative coughing or postoperative nausea and vomiting was found in two groups. Conclusions:The combination of remimazolam and propofol provides better efficacy than propofol alone when used for sedation in the pediatric patients undergoing outpatient dental root canal treatment.