Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

Jinlingzi San is a formula frequently used in treating pain syndrome， first recorded in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu in the Jin Dynasty. Jinlingzi San is composed of 2 Chinese medicinals Toosendan Fructus and Corydalis Rhizoma with a concise composition and exact clinical efficacy， having been included in the Catalogue of Ancient Classical Formulas （Second Batch： Han Chinese Medicine）. The formula name， historic evolution， medicine origins， composition， dosage， decocting methods， and ancient and modern clinical application were sorted out and analyzed with the bibliometric method. A total of 209 pieces of information were collected from ancient books and literature. After screening， 49 pieces of effective data involving 45 ancient books were included. Results showed that the name of Jinlingzi San was first recorded in Secret Formulas of the Yang Family written by Yang Tan in the Southern Song Dynasty and developed into 3 other versions of the decoction. The Jinlingzi San included in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu invariably plays a dominant role. As for the 3 other versions， although they have the same name of Jinlingzi San， their composition and indications are different from those of the original formula， which were therefore viewed as prescriptions based on Jinlingzi San and also included in the research. The medicine origins and processing of Jinlingzi San are suggested： Toosendan Fructus is the dry mature fruit of Melia toosendan of Meliaceae， and the crude is used after cleansing without putamen. Corydalis Rhizoma is the dry tuber of Corydalis yanhusuo of Papaveraceae， which is used after impurity removal， cleaning， and drying. Depending on the conversion from the measurement system in the Jin Dynasty to modern measurement， it is suggested that Toosendan Fructus and Corydalis Rhizoma （41.3 g each） are ground into fine powder， and one dose includes 12.39 g of the powder， which should be taken with an appropriate amount of wine. If wine is not suitable for the patient， the decoction can also be taken with warm water. Jinlingzi San has the effects of soothing the liver， discharging heat， and activating blood to stop pain. As recorded in ancient books， Jinlingzi San is specialized in treating heart pain caused by reversal heat， chest and abdominal pain， hypochondriac pain， jaundice， hernia， and other diseases. Modern studies have shown that modified Jinlingzi San can be used in treating diseases involving the digestive system， the integumentary system， the gynecological system， the reproductive system， and other systems and has wide clinical application in treating epigastric pain， herpes zoster， dysmenorrhea， and other diseases. This study has made clear the key information of Jinlingzi San by textual research of ancient books and literature in the hope of providing a theoretical reference for the clinical application， set prescriptions， and new drug development.

The psychoactive properties of cannabinoids are well known,and there are controversies over whether cannabinoids can be used for therapeutic purposes worldwide.Δ9-tetrahydrocannabinol(THC)is the main psychoactive substance in cannabis.The neurological mechanisms of THC were only recently discovered,and its neurological mechanism of action is still not fully understood.The blood-brain barrier(BBB)is a very important structure protecting the brain and is the first line of defense preventing foreign substances from entering the brain.THC's lipophilic nature and its interaction with the endocannabinoid system make it more likely to act on the BBB.In this paper,we review the neurotoxic effects of THC,focusing on its effect and mechanism of action on the BBB,and provide a theoretical basis for studies elucidating the neural mechanism of THC.

Objective:To analyze the advantages of human epididymis protein 4 (HE4) compared with traditional tumor markers in the diagnosis and treatment of lung cancer.Methods:From February 2021 to June 2022, 230 lung cancer patients (138 males, 92 females; age (61.1±12.3) years), 96 benign lung disease patients (62 males, 34 females; age (60.2±14.8) years; including 43 cases of lung benign placeholder and 53 cases of pulmonary infection), and 60 healthy volunteers (40 males, 20 females; age (62.8±11.4) years) from the Second Affiliated Hospital of Soochow University were prospectively collected. Serum HE4, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen (CA)125 were detected by electrochemical analysis. The expression of HE4 in tumor tissues of 55 patients with lung cancer was detected by immunohistochemical method. χ2 test, Mann-Whitney U test, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. The diagnostic efficiencies of HE4 and other tumor markers were evaluated by ROC curve analysis and the difference of AUCs was analyzed by Delong test. Results:The positive expression rate of HE4 in adenocarcinoma tissue was significantly higher than that in non-adenocarcinoma tissue (93.1%(27/29) vs 23.1% (6/26); χ2=28.01, P<0.001). The level of serum HE4 in the lung cancer group (70.70(51.93, 109.05) pmol/L) was significantly higher than that in the pulmonary benign placeholder group (59.80(48.20, 73.50) pmol/L) and the healthy control group (55.25(44.60, 74.25) pmol/L), and that in the pulmonary infection group (97.90(76.62, 155.00) pmol/L) was higher than that in the lung cancer group ( H=46.19, all P<0.008 (Bonferroni correction method)). The levels of serum HE4 were significantly different in age, sex, smoking, disease stage and pathological types in early stage ( z values: from -5.07 to 9.83, all P<0.05). The ROC curve analysis indicated that the optimal cut-off value of serum HE4 for diagnosing lung cancer was 79.22 pmol/L, with the sensitivity and specificity of 41.30%(95/230) and 83.33%(50/60). Compared with other traditional tumor markers, serum HE4 and CA125 showed the higher diagnostic value (AUC CA125 (0.695)>AUC HE4(0.656)>AUC CEA(0.614)>AUC CYFRA21-1(0.599)>AUC ProGRP (0.501)>AUC NSE (0.470)). The combination of HE4 with other traditional tumor markers significantly improved the diagnostic efficacy (AUC=0.750; z=2.75, P=0.006). Conclusions:HE4 is highly expressed in lung adenocarcinoma by immunohistochemistry. Serum HE4 exhibits a great application value in the differential diagnosis between benign and malignant pulmonary nodules, and plays an important role in assessment of patients′ conditions.

OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.

Objective:To formulate surgical strategies and guide the implementation of laparoscopic anatomical hepatectomy with preoperative simulative resection.Methods:Twenty-two cases of hepatocellular carcinoma undergoing laparoscopic lobe, segment, subsegment and combined segment liver resection following preoperative simulative resection from Sep 2020 to Jan 2022 were enrolled in this study retrospectively.We observed and analyzed the operation time,intraoperative blood loss,postoperative hospital stay and postoperative complication.Results:All patients underwent laparoscopic hepatectomy successfully according to the preoperative simulative resection plan without conversion, some of them adjusted plan according to preoperative simulative resection. The median operation time was 170.0 min, the median intraoperative blood loss was 150.0 ml, the median times of pringle maneuver was done on 4 episodes, and the median postoperative hospital stay was 6.5 days. There were no severe postoperative complications in all cases.Conclusion:Preoperative simulative resection can plan the range of surgical resection accurately by visualizing important anatomical structures,greatly helping the actual surgical hepatectomy.

Circular RNA (circRNA) is a kind of RNA with a circular structure. The unique structure of circRNA endows it with various cell biological functions and characteristics. It has become a research hotspot recently. CircRNA can play a role via mechanisms, such as microRNA (miRNA) sponge, RNA binding protein, peptide translation and regulation of gene transcription. CircRNA was found to be associated with disc degeneration, spinal cord injury, scoliosis, and facet arthritis. Some techniques, including bioinformatics and molecular biology techniques, microarray and high-throughput sequencing, can be used to predict and to discover disease-related circRNA, aiming to evaluate whether circRNA can be used as a molecular biomarker for spinal and spinal cord diseases. Based on the current role of circRNA, the corresponding therapeutic strategies have been carried out in experimental animals, which can provide theoretical basis for gene therapy. At present, the researches in circRNA for spinal and spinal cord diseases are still insufficient compared with those in other fields. Currently, the main direction focuses on the miRNA sponge mechanism of circRNA. Due to the variety of diseases in spinal surgery, the research progress of circRNA is also varied. In addition, the development of microarray and high-throughput sequencing technology have greatly promoted the researches in circRNA. The availability of public database is of great significance in the study. The present review summarized the current researches status of circRNA in spinal and spinal cord diseases, aiming to deepen understanding of circRNA in spinal and spinal cord diseases.

Objective:To explore the clinical effects of simultaneous reconstruction of multiple joint scar contracture deformity of limb.Methods:From January 2010 to June 2018, 24 patients with multiple joint scar contracture deformity of the same limb were reconstructed in simultaneous operations in Xiangya Hospital of Central South University, including 16 males and 8 females, aged 3-42 years, with 15 patients having deformities in the upper limbs and 9 patients having deformities in the lower limbs. One operation was performed to repair contracture deformity of axillary fossa and elbow in 3 patients, cubital fossa and palmar of wrist in 4 patients, cubital fossa and hand in 5 patients, palmar of wrist, palm, and palmar of finger in 3 patients, groin and medial knee in 2 patients, popliteal fossa and posterior ankle in 1 patient, and anterior ankle and dorsum of foot in 6 patients. After the release of various joint scar contractures, the area of skin defect was 140 to 580 cm 2. Autologous full-thickness skin grafts were used in 7 patients, autologous medium-thickness skin grafts were used in 4 patients, autologous full-thickness skin grafts combined with local skin flaps were used in 9 patients, and allogeneic acellular dermal matrix and autologous thin skin grafts were used in 4 patients. Comprehensive measures for rehabilitation were taken and the survival of the skin graft was observed after operation. Six months to eight years after the operation, all the patients were followed up for the functions of the affected limbs, among which the functions of the upper limbs were evaluated according to the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. The joint mobility, walking, and squatting function of lower extremity were examined after operation. Recurrence of contractures in all the affected limbs and reoperation were recorded. Results:The grafts survived after operation in 22 patients. Two patients had necrosis in small full-thickness skin area, of which one was healed by skin grafting after debridement, and the other one was healed after dressing changes. The deformity of scar contracture at each repaired joint was completely or partially corrected. During a follow-up for 6 to 96 months, the upper limb functions of 15 patients were rated excellent in 12 patients and good in 3 patients. Among the 9 patients of lower limb scar contractures, except for one 3-year-old child who experienced recurrence of medial knee scar contracture and underwent surgical release and skin grafting 5 years later, the remaining 8 patients basically recovered normal joint functions with pretty good outcomes.Conclusions:For continuous scar contracture deformity of multiple joints of the same limb, simultaneous surgical release and skin grafting can reduce operation frequency and obtain better outcomes of surgical operation.

Objective: To re-evaluate the reliability and validity of the Adolescent Self-rating Life Events Checklist (ASLEC), and to adapt to the further application to middle school students in rural China. Methods: A stratified random cluster sampling method was applied to select 15 607 adolescents from grade 7th to grade 12th in 15 rural areas of 5 provinces(Anhui Province, Yunan Province, Guangdong Province, Hei Longjiang Province, Hubei Province), and they were recruited to complete our Questionnaires. Results: The revised version (ASLEC-R) consisted of 5 dimensions (punishment, interpersonal relationship, academic pressure, loss and adaptation problem), 25 items after deleting items 5 and 17 through exploratory factor analysis and confirmatory factor analysis, which could accounted for 55.22% of the total variance. The fit indices were RMSEA=0.06，GFI=0.91，CFI=0.88，TLI=0.86，NFI=0.88，AGFI=0.88，HOELTER 0.05=261. The Cronbach’s α and Spearman-Brown splithalf reliability coefficient of the whole scale were 0.92 and 0.87, respectively，and the test-retest reliability was 0.84. ASLEC-R had better reliability than the unrevised version. The results of five-joint item analyses showed that each item improved in terms of indiscrimination, relevance, contribution, homogeneity and sensitivity. The correlation coefficients with BWAQ and EI subscale were 0.38 and -0.36 respectively. Conclusion ASLEC-R has good reliability and validity , and it is worth being applied to the Chinese rural areas.