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 To investigate the therapeutic mechanism of Guiyuan Decoction(GYD,with Rehmanniae Radix as the principal herb)in Sj?gren's syndrome(SS).Methods Active components of GYD were retrieved from network pharmacology databases,and potential targets for SS were predicted.Common targets were identified via Venn analysis,followed by construction of a"herb-compound-target"network.Protein-protein interaction(PPI)networks were generated,and Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using the DAVID platform.Molecular docking was employed to evaluate binding affinities between core components and key target proteins.In vivo and in vitro experiments were conducted to validate predictions based on literature and docking results.Results A total of 318 bioactive components in GYD and 148 disease-related overlapping targets were identified.GO and KEGG analyses yielded 921 functional terms and 159 signaling pathways,respectively.Molecular docking revealed stigmasterol exhibited the strongest binding affinity with caspase-3(CASP3),while quercetin,kaempferol,andβ-sitosterol also showed robust interactions with core targets.Experimental validation demonstrated that both GYD and its active constituent stigmasterol significantly downregulated protein expression levels of CASP3,NLR family pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),interleukin-1β(IL-1 β),and Caspase-1 in submandibular gland tissues of Sj?gren's syndrome mice and in lipopolysaccharide(LPS)-stimulated submandibular gland cells.Furthermore,they effectively reduced the concentrations of interleukin-6(IL-6),interleukin-1β(IL-1 β),and tumor necrosis factor-α(TNF-α)in peripheral blood and cell culture supernatants of Sj?gren's syndrome mice.Conclusion Integrated network pharmacology and molecular docking suggest that GYD exerts anti-SS effects primarily via stigmasterol-mediated modulation of CASP3.Experimental evidence confirms that GYD and stigmasterol attenuate inflammatory responses and may ameliorate SS by targeting CASP3 to suppress NLRP3 inflammasome activation.

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Objective:To investigate the anatomic classification and reconstruction of right intrahepatic bile duct in the donor liver of split liver transplantation (SLT).Methods:The retrospective and descriptive study was constructed. The clinical data of 85 patients who underwent SLT in the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to January 2022 were collected. There were 65 males and 20 females, aged 45(range, 1-82)years. Observation indicators: (1) surgical conditions; (2) anatomy of right intrahepatic bile duct; (3) bile duct reconstruction; (4) postoperative biliary complications; (5) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3).Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical conditions. Of the 85 donor livers, 11 donor livers were split between the left and right hemilivers, and 74 donor livers were split between the classic right trilobe and left lateral lobe. The cold ischemia time of 85 donor livers was 291(273, 354)minutes, and the operation time, anhepatic phase time and volume of intraoperative blood transfusion of 85 recipients were (497±97)minutes, 51(40, 80)minutes and 8(7, 12)U. (2) Anatomy of right intrahepatic bile duct. Of the 85 donor livers, there were 47 donor livers with classic bile duct anatomical model (type 1), of the ratio as 55.3%(47/85), and 38 donor livers with anatomical variants, of the ratio as 44.7%(38/85). Of the 38 donor livers with anatomical variants, 7 donor livers were type 2, 16 donor livers were type 3a, 2 donor livers were type 3b, 2 donor livers were type 3c, 1 donor liver was type 4, 3 donor livers were type 5a, 4 donor livers were type 5b, 3 donor livers were type 6. For bile duct splitting patterns of the 85 donor livers, 84 donor livers were split with the main trunk of common hepatic duct preserving in the right hemiliver or right trilobe, and 1 donor liver were treated with complete left and right hemiliver splitting to preserve the main trunk of the common hepatic duct in the left hemiliver and the right hemiliver in the right hepatic duct (type 1 bile duct anatomical model). There were 84 donor livers with only one bile duct opening, and 1 donor liver with two bile duct openings (type 3c bile duct anatomical model). (3) Bile duct reconstruction. Of the 85 recipients, there were 69 recipients with common bile duct end-to-end anastomosis to common bile duct of donor liver (38 donor livers with type 1 bile duct anatomical model, 5 donor livers with type 2 bile duct anatomical model, 14 donor livers with type 3a bile duct anatomical model, 2 donor livers with type 3b bile duct anatomical model, 1 donor liver with type 4 bile duct anatomical model, 3 donor livers with type 5a bile duct anatomical model, 4 donor livers with type 5b bile duct anatomical model, 2 donor livers with type 6 bile duct anatomical model), 11 recipients with jejunum anastomosis to common bile duct of donor liver (7 donor livers with type 1 bile duct anatomical model, 2 donor livers with type 2 bile duct anatomical model, 1 donor liver with type 3c bile duct anatomical model, 1 donor liver with type 6 bile duct anatomical model), 3 recipients with jejunum anastomosis to common hepatic duct of donor liver (1 donor liver with type 1 bile duct anatomical model, 2 donor livers with type 3a bile duct anatomical model), 1 recipient with jejunum anastomosis to right hepatic duct of donor liver (type 1 bile duct anatomical model), 1 recipient with common hepatic duct end-to-end anastomosis to right posterior branch of donor liver combined with jejunum of the recipient Roux-en-y anastomosis to common hepatic duct of donor liver (type 3c bile duct anatomical model). (4) Postoperative biliary complications. Of the 85 recipients, 6 cases had postoperative biliary complications, with an incidence of 7.1% (6/85). Of the 6 recipients with postoperative biliary complications, there were 5 recipients with donor liver with type 1 bile duct anatomical model, including 3 cases undergoing postoperative biliary stricture with biliary leakage and 2 cases undergoing postoperative biliary anastomotic stricture, 1 recipient with donor liver with type 3b bile duct anatomical model and undergoing postoperative biliary anastomotic stricture and bile leakage in the liver section. Cases with biliary complications were 5 in the 47 recipients with donor liver with classic bile duct anatomical model and 1 in the 38 recipients with donor liver with anato-mical variants, showing no significant difference between them ( P>0.05). (5) Follow-up. There were 83 recipients receiving followed up for 52(12,96)months. During the follow-up period, 2 recipients died due to non-biliary complication factors (1 donor liver with type 1 bile duct anatomical model and 1 donor liver with 3a bile duct anatomical model). Conclusion:The anatomical classification of right intrahepatic bile duct of donor liver in SLT is mainly classical bile duct anatomical model, and the bile duct reconstruction scheme is mainly common bile duct of donor liver end-to-end anasto-mosis to common bile duct of recipient.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective To investigate air radioactivity contamination, surface contamination, ambient dose equivalent rates, and radiation doses to individuals in the treatment room during ¹⁷⁷Lu-DOTATATE therapy. Methods A ward for ¹⁷⁷Lu-DOTATATE therapy was selected in the nuclear medicine department of a general hospital. Air and surface radioactivity samples were collected before and after therapy for four patients. Ambient dose equivalent rates were measured around the four patients following the initiation of ¹⁷⁷Lu-DOTATATE therapy. Measurements were taken at distances of 0.1, 0.3, 0.5, and 1−4 m (with 0.5 m intervals) from the right lateral midsection of the patient’s torso. The measurement time points included 5, 15, and 30 min after initiation of administration, as well as 0−4 h (with 1 h intervals), 24 h, and 48 h post-administration. Radiation exposure doses for personnel at different distances from the patients were calculated for each time interval. Results The results of radioactive aerosol detection for all four patients during and after the administration of ¹⁷⁷Lu-DOTATATE were similar to those before administration. Surface contamination was not detected at the measurement locations except for patient number 2. The ambient dose equivalent rates increased with increasing injection dose during the administration. However, the ambient dose equivalent rates decreased significantly within one hour after administration. At the end of the administration, the average ambient dose equivalent rate at a distance of one meter for the four patients was 42.931 μSv/h. From the start of administration to four hours post-administration, personnel maintaining a distance of one meter from the patient received a total radiation dose of 167.64 μSv. Conclusion Air radioactivity contamination does not occur during ¹⁷⁷Lu-DOTATATE therapy. However, measures should be taken before the commencement of therapy to address potential surface contamination. Both accompanying persons and healthcare staff receive radiation doses below the stipulated dose constraints throughout the treatment process. Therefore, it is necessary to implement appropriate measures to minimize the radiation exposure of healthcare staff.

Objective To investigate air radioactivity contamination, surface contamination, ambient dose equivalent rates, and radiation doses to individuals in the treatment room during ¹⁷⁷Lu-DOTATATE therapy. Methods A ward for ¹⁷⁷Lu-DOTATATE therapy was selected in the nuclear medicine department of a general hospital. Air and surface radioactivity samples were collected before and after therapy for four patients. Ambient dose equivalent rates were measured around the four patients following the initiation of ¹⁷⁷Lu-DOTATATE therapy. Measurements were taken at distances of 0.1, 0.3, 0.5, and 1−4 m (with 0.5 m intervals) from the right lateral midsection of the patient’s torso. The measurement time points included 5, 15, and 30 min after initiation of administration, as well as 0−4 h (with 1 h intervals), 24 h, and 48 h post-administration. Radiation exposure doses for personnel at different distances from the patients were calculated for each time interval. Results The results of radioactive aerosol detection for all four patients during and after the administration of ¹⁷⁷Lu-DOTATATE were similar to those before administration. Surface contamination was not detected at the measurement locations except for patient number 2. The ambient dose equivalent rates increased with increasing injection dose during the administration. However, the ambient dose equivalent rates decreased significantly within one hour after administration. At the end of the administration, the average ambient dose equivalent rate at a distance of one meter for the four patients was 42.931 μSv/h. From the start of administration to four hours post-administration, personnel maintaining a distance of one meter from the patient received a total radiation dose of 167.64 μSv. Conclusion Air radioactivity contamination does not occur during ¹⁷⁷Lu-DOTATATE therapy. However, measures should be taken before the commencement of therapy to address potential surface contamination. Both accompanying persons and healthcare staff receive radiation doses below the stipulated dose constraints throughout the treatment process. Therefore, it is necessary to implement appropriate measures to minimize the radiation exposure of healthcare staff.

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 study the relationship between circulating inflammatory proteins and liver cancer by Mendelian randomization.Methods:Data from the genome-wide association study (GWAS) of 91 circulating inflammatory proteins were sourced from the GWAS Catalog, involving 14 824 participants of European ancestry from 11 cohorts. Summary statistics for liver cancer were obtained from the GWAS database, encompassing a total sample of 197 611 cases, a two-sample Mendelian randomization analysis was conducted to evaluate the relationship between 91 circulating inflammatory proteins and liver cancer. Among them, inverse variance weighting, weighted median method, MR-Egger, simple mode, and weighted mode were the main analysis methods. Using odds ratio (OR) values to evaluate the causal relationship between them. Cochran Q-test, MR-PRESSO, MR-Egger intercept, and "leave-one-out" analyses were used for sensitivity analysis. Reverse MR, MR-Steiger tests were employed to rule out the influence of reverse causality.Results:Among the circulating 91 inflammatory proteins, C-C motif chemokine 20 ( OR=1.28, 95% CI: 1.01-1.62), CD40 receptor ( OR=1.31, 95% CI: 1.00-1.28), fibroblast growth factor 21 ( OR=1.47, 95% CI: 1.18-1.83), glial cell line-derived neurotrophic factor ( OR=1.29, 95% CI: 1.08-1.54), interleukin-13 (IL-13) ( OR=1.24, 95% CI: 1.02-1.50), IL-20 levels ( OR=1.78, 95% CI: 1.30-2.44), IL-20 receptor subunit alpha ( OR=1.43, 95% CI: 1.06-1.93), and matrix metalloproteinase-10 ( OR=1.21, 95% CI: 1.04-1.39) have positive causal relationship with the occurrence of liver cancer. And IL-1 alpha ( OR=0.83, 95% CI: 0.71-0.96), IL-24 ( OR=0.68, 95% CI: 0.47-0.99), leukemia inhibitory factor ( OR=0.77, 95% CI: 0.60-0.98) and stem cell factor ( OR=0.87, 95% CI: 0.78-0.97) showed negative causal relationship with the occurrence of liver cancer. Heterogeneity tests for all 12 circulating inflammatory proteins revealed no outliers. Sensitivity analyses consistently demonstrated robustness, with no evidence of pleiotropy observed. Neither reverse MR nor MR-Steiger tests supported the existence of a reverse causal relationship between inflammatory proteins and liver cancer. Conclusion:The C-C motif chemokine 20, CD40L receptor, fibroblast growth factor 21, glial cell line-derived neurotrophic factor, IL-13, IL-20, IL-20 receptor subunit alpha, MMP-10, IL-1 alpha, IL-24, leukemia inhibitory factor, and stem cell factor may be causally related to the development of liver cancer.