Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

Objective Investigate the expression level and clinical significance of microRNA-223-3p(miR-223-3p)in the serum of pregnant women with preterm premature rupture of membranes(PPROM).Methods A total of 91 pregnant women who underwent cesarean delivery at the Xuzhou Maternal and Child Health Hospital affiliated with Xuzhou Medical University between April and September 2023 were selected for the study.This included 60 cases of PPROM and 31 cases of term normal pregnant women as the research subjects.The study group was divided based on the pathological results of the membranes into:PPROM group without histological chorioamnionitis(HCA)(PPROM group,n = 37),and PPROM group with HCA(PPROM+HCA group,n = 23).Serum samples from pregnant women were collected before hospital treatment,and the expression level of miR-223-3p in the serum was detected by quantitative real-time PCR(qRT-PCR).The levels of inflammatory factors such as IL-1β,IL-6,IL-8,and TNF-α in the serum were measured by enzyme-linked immunosorbent assay(ELISA).Results The expression level of miR-223-3p in the serum of the PPROM+HCA group was significantly higher than that of the PPROM group and the normal group(P＜0.05).The expression levels of IL-1β,IL-6,IL-8,and TNF-α in the serum of the PPROM+HCA group were also significantly higher than those of the PPROM group and the normal group(P＜0.05).There was a positive correlation between the expression level of miR-223-3p in the serum of the PPROM+HCA group and the expression levels of IL-1β,IL-6,IL-8,and TNF-α(r = 0.553,0.505,0438,0.656,P＜0.05).Conclusion The upregulation of miR-223-3p in the serum of pregnant women with PPROM+HCA is associated with the severity of inflammation in PPROM.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

Objective:To investigate the effects of apolipoprotein E (APOE) ε4 allele on β-amyloid (Aβ) deposition in subcortical structures and functional connectivity (FC) between brain regions in patients with Alzheimer′s disease (AD). Methods:Forty-three patients with probable mild/moderate AD were prospectively enrolled from the First Medical Centre, Chinese PLA General Hospital between January 2023 and October 2023, including 23 APOE ε4+ patients (12 males and 11 females, age (74.8±8.4) years), 20 APOE ε4- patients (14 males and 6 females, age (77.6±8.9) years) and 20 normal cognitive volunteers (NC) (15 males and 5 females, age (75.3±6.2) years). All subjects underwent 11C-Pittsburgh compound B (PIB) PET/MR brain imaging. The differences of gray matter volume (GMV) in subcortical structures (hippocampus, amygdala) among the three groups were analyzed by one-way analysis of variance and least significant difference (LSD) t test. Independent-sample t test and Pearson correlation analysis were used to analyze difference in Aβ deposition between APOE ε4+ patients and APOE ε4- patients, and the correlation between subcortical structure and brain FC. Results:The GMV of bilateral amygdala between NC group and APOE ε4+ gene carrier group, and between APOE ε4+ and APOE ε4- gene carrier groups were significantly different ( F=6.43, P=0.002; P values: 0.002, 0.003). Significant difference of GMV was observed in the bilateral hippocampus among three groups ( F=5.34, P=0.030). Abnormal PIB uptake was detected in both the hippocampus and amygdala of both APOE ε4+ and APOE ε4- gene carrier groups, with a more pronounced effect observed in the APOE ε4+ group ( t values: 3.14, 2.19, P values: 0.032, 0.009). Taking the hippocampus as the seed point, there was no obvious abnormality in the whole brain connectivity map among APOE ε4+, APOE ε4- carriers and NC groups. With the amygdala as the seed point, the whole brain connectivity in the APOE ε4+ gene carrier group was significantly reduced, and the connectivity between the amygdala and the cingulate gyrus, parietal lobe and temporal lobe was significantly reduced in the APOE ε4+ gene carrier group compared with NC group, while the connectivity between the amygdala and the whole brain was not significantly reduced in the APOE ε4- gene carrier group. Aβ deposition in amygdala was positively correlated with FC coefficients of frontal brain regions, gyrus rectus, right middle occipital gyrus and left temporal lobe ( r values: 0.56-0.70, all P<0.05). Conclusion:APOE influences GMV and Aβ deposition of hippocampus and amygdala, and FC of amygdala, and may be involved in the pathological mechanism of cognitive impairment.

Objective:To evaluate the potential of 177Lu-prostate specific membrane antigen (PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and compare it with 177Lu-PSMA-I&T. Methods:177Lu-PSMA-3Q was prepared and the quality control and stability testing were performed. Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were conducted in normal BALB/c mice and 22Rv1 tumor-bearing mice. SPECT imaging was performed on 2 patients (60 and 76 years old) with mCRPC from Chinese PLA General Hospital at 24, 72, and 120 h after injection of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T ((7.40±0.74) GBq). Data were analyzed by using independent-sample t test. Results:177Lu-PSMA-3Q was prepared with the total activity of 74 GBq, the yield rate of 95% (uncorrected), and the radiochemical purity was still above 95% after 168 h at room temperature. The distribution half-lives of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were (0.75±0.22) and (0.86±0.19) min, and the clearance half-lives were (24.74±3.77) and (29.53±3.42) min. Biodistribution of normal mice showed that the uptake values in the liver, lungs, and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177Lu-PSMA-I&T ( t values: 4.24-8.36, all P<0.05). The tumor uptake of 177Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177Lu-PSMA-I&T ((0.856±0.183) vs (0.579±0.126) percentage activity of injection dose per gram of tissue (%ID/g); t=2.78, P=0.024) in 22Rv1 tumor-bearing mice. The rapid clearance pattern resulted in a higher tumor/muscle (T/M) ratio for 177Lu-PSMA-3Q (99.604±11.106), which was significantly higher than that for 177Lu-PSMA-I&T (45.078±10.444; t=7.80, P<0.001). According to SPECT imaging of patients with mCRPC, the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h, with significant difference ( t=7.62, P=0.002). Conclusion:177Lu-PSMA-3Q is easy to label, and has high yield and radiochemical purity, good stability, excellent biological performance, good targeting ability in patients, longer retention time, and fast background clearance rate, which is an ideal prostate cancer treatment drug targeting PSMA.

This review introduces the daily management practices related to laboratory animal licensing in Hubei Province and the supervision processes during and after licensing.We consider the current status of laboratory animal license management,achievements,problems,and countermeasures in Hubei Province,with a focus on analyzing the legislative situation for laboratory animals,the issuance and distribution of permits,the scale of facilities,and the composition of employees.The number of laboratory animal licenses issued in Hubei Province has recently been increasing year by year,and the numbers of animals produced and used by licensed units have also continued to rise.Although the related industries are flourishing however,there are some regulatory deficiencies.This paper considers the perspective of biosafety,combined with the problems encountered in license management,and proposes relevant safety supervision countermeasures and suggestions to promote the development of the laboratory animal industry in Hubei Province.

Objective To construct a risk assessment scale for postoperative delirium(POD)in elderly patients undergoing hip and knee joint replacement and evaluate the effect.Methods A total of 474 elderly patients undergoing hip and knee arthroplasty from March 2021 to May 2022 were collected as the training set,and a total of 153 the homogeneous patients from January 2022 to May 2022 were collected as the validation set.The patients were divided into two groups based on whether or not POD occurred:non-POD group and POD group.Risk factors of POD in the training set were analyzed by univariate analysis and multifactorial logistic regression.The consistency of the model was evaluated by Homser-Lemeshow goodness of fit test.The postoperative delirium risk assessment scale was established after the selected variables as-signed value according to OR value,and the predictive efficacy of the scale was evaluated by receiver oper-ating characteristic(ROC)curve.The patients in the training set and the validation set were divided into two groups according to the cut-off value:high-risk and low-risk.The incidence rate of POD with different risk stratification was calculated and the applicability of the risk assessment scale was evaluated.Results Fifty-eight patients(12.2%)with POD in the training set,and nineteen patients(12.4%)with POD in the validation set.Multifactor logistic regression showed that age≥85 years,ASA physical status Ⅲ or Ⅳ,the mini-mental state examination(MMSE)score≤24 points,preoperative sleep disorder,comorbid neu-rological disorders,use of general anesthesia,and non-use of dexmedetomidine were independent risk factors of POD.The POD risk assessment scale was then published based the seven risk factors.The ROC curve showed that the area under the curve(AUC)for this scale to predict the risk of POD was 0.956(95%CI 0.937-0.975),and the risk stratification was performed with a cut-off value of 44.5 points,which divided the patients into low-risk and high-risk.Compared with low-risk,the incidence rate of POD in high-risk patients group was significantly increased(P＜0.001).Conclusion A risk assessment scale based on the seven risk factors:age≥85 years,ASA physical status Ⅲ or Ⅳ,MMSE score≤24 points,preoperative sleep disorder,combined neurological disease,use of general anesthetic modality,and non-use of dexmedetomidine,can effectively identify elderly patients undergoing hip and knee replacement who are at high risk of developing POD.

Objective: To measure the position of the mandibular nerve canal at the mandibular second molar by CBCT image data, analyze the theoretical implantation range of trans-alveolar implantation, and provide a theoretical solution to insufficiency of posterior mandibular bone volume in clinical practice. Methods: Eighty patients with missing mandibular second molars whose vertical bone height of the edentulous area was less than 9 mm were selected for CBCT image measurement, and the distances from the mandibular nerve canal to the buccal cortex, lingual cortex, and alveolar crest were measured to simulate trans-inferior alveolar nerve implantation. The angular range of the buccolingual inclination of the implant was also measured. Results: The distances from the mandibular nerve canal to the buccal cortex, lingual cortex and alveolar crest at the mandibular second molar were(6.913±1.222)mm, (2.859±0.891)mm and (7.991±0.783)mm, respectively. The distance from the mandibular nerve canal to the buccal cortex was significantly greater than that to the lingual cortex. And, 75% of the patients could be implanted by the inferior alveolar nerve. The minimum angle of buccolingual inclination of the simulated implant was 19.360°±7.086°, and the maximum angle was 39.462°±6.924°. Conclusion The mandibular nerve canal at the mandibular second molar is inclined toward the lingual side, which ensures sufficient buccal bone volume. Most patients with severe mandibular atrophy can still adopt implants of conventional length by trans-inferior alveolar nerve implantation to keep a safe distance from the nerve canal.

Objective:To investigate the role and underlying mechanisms of inhibiting high mobility group box-1 (HMGB1) in the expression of matrix metalloproteinase-9 (MMP-9) in spinal cord astrocytes (AS) in rats after spinal cord injury (SCI).Methods:After an SCI model was established in Sprague-Dawley (SD) rats using a modified Allen's Weight-Dropping method and ethyl pyruvate (EP) or glycyrrhizin (GL) was used to inhibit the effect of HMGB1, the rats were divided into a sham group, an SCI group, an SCI+EP (50 mg/kg) group, and an SCI+GL (100 mg/kg) group. The expression levels of glial fibrillary acid protein (GFAP) and MMP-9 in spinal cord AS were observed. After the spinal cord AS in SD rats was cultured and incubated by the oxygen-glucose deprivation/reoxygenation (OGD/R) procedure, the expression of MMP-9 protein was detected at 6 h/R 6 h, 12 h, 24 h, and 48 h after OGD. The time point with the highest expression was chosen in the subsequent experiments as an OGD/R group. HMGB1 was inhibited by HMGB1 shRNA or EP to observe the effect of HMGB1 on the expression of MMP-9 protein in AS treated with OGD/R. Then, toll-like receptor 4 (TLR4) inhibitor, TIR-domain-containing adaptor inducing interferon- β (TRIF) inhibitor, and nuclear factor-kappa B (NF- κB) inhibitor were used to investigate the effects of TLR4/TRIF/NF- κB signaling pathway during the regulation of HMGB1 on MMP-9 in vitro. Results:Western blot showed that the expression of MMP-9 protein in the spinal cord was significantly increased in rats at 1 d after SCI, and the expression of MMP-9 protein in the SCI+EP group and the SCI+GL group was significantly lower than that in the SCI group ( P<0.001). Immunofluorescence showed that GFAP and MMP-9 proteins were co-localized in the spinal cord after SCI, and the expression of GFAP and MMP-9 proteins in the SCI+EP and SCI+GL groups was significantly lower than that in the SCI group ( P<0.05). Since the expression of MMP-9 protein in the spinal cord AS cultured in vitro was significantly higher in the OGD 6h/R 12h group than that in the normal group and the OGD 6h/R 6h, 24, and 48 h groups, the OGD 6h/R 12h was taken as the OGD/R group. The MMP-9 protein expression in AS in the OGD/R+HMGB1 shRNA group and the OGD/R+EP group was significantly lower than that in the OGD/R group ( P<0.001). In the cultured AS, moreover, inhibiting TLR4, TRIF, and NF- κB reduced MMP-9 protein expression after OGD 6 h/R 12 h when compared with that in the OGD/R group ( P<0.001). Conclusions:HMGB1 inhibition may result in a reduction in MMP-9 expression both in the spinal cord AS in SCI rats and in AS after OGD/R treatment in vitro. HMGB1 may regulate MMP-9 protein expression in AS after OGD/R treatment via the TLR4/TRIF/NF- κB signal pathway.