[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Objective: To analyze the iodine nutritional status of children aged 8-10 in Baoshan City, so as to comprehensively evaluate the effectiveness of eliminating and consolidating iodine deficiency disorders in Baoshan City. Methods: From 2018 to 2024, a stratified random sampling method was used to sample 7 363 non boarding children aged 8-10 from 35 survey sites in 5 counties of Baoshan City (Longyang County, Shidian County, Changning County, Tengchong City, Longling County). The salt iodine content and urinary iodine concentration were detected, and the thyroid volume of children was measured by ultrasound. Group comparison was conducted by using Mann-Whitney U test, Kruskal-Wallis H test, and Chi square test. Spearman rank correlation analysis was used to investigate the correlation of salt iodine, urinary iodine and thyroid volume. Results: A total of 7 361 samples of household edible salt for children were detected. The iodized salt coverage rate was 99.70%, the qualified iodized salt consumption rate was 97.02 %. The proportion of unqualified iodized salt fluctuated and decreased from 3.14% in 2018 to 2.14% in 2024. The median iodine content of household edible salt for children was 23.70 (21.60, 25.80) mg/kg. The median urinary iodine of children was 217.41 (152.40, 294.59) μg/L, and the proportions of iodine deficiency, adequate iodine, and iodine excess were 9.75 %, 66.66%, and 23.58%, respectively. There were statistically significant differences in the median urinary iodine of children among different years, ages, genders and before and after the supply of non iodized salt ( Z/H =134.88, 11.04,-4.28,-2.66, all P < 0.01). An average thyroid volume of children was 3.32 (2.77, 3.93) mL, with a goiter rate of 1.91%. Before and after the implementation of non iodized salt supply in Baoshan City in 2023, there were no statistically significant differences in the median iodine content of household edible salt and the goiter rate of children ( Z/χ 2=-1.54, 3.25, both P >0.05), but there were statistically significant differences in the qualified status of iodized salt, the median urinary iodine, and the frequency distribution of urinary iodine ( χ 2/Z =15.53,-2.66, 10.14, all P <0.05). Salt iodine was positively correlated with urinary iodine ( r =0.04) and negatively correlated with thyroid volume ( r =-0.07), and urinary iodine was negatively correlated with thyroid volume ( r =-0.03) (all P < 0.05 ). The thyroid volume of children consuming iodized salt was larger than that of children consuming non iodized salt ( H = 9.99 ), and there were statistically significant differences in thyroid volume among children with different urinary iodine levels ( H =15.13) (both P <0.01). Conclusions From 2018 to 2024, the overall iodine nutritional level of children aged 8-10 in Baoshan City is at an adequate level. The elimination status of iodine deficiency disorders has been continuously consolidated.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments.Methods:Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases; R language software was used to map the intersection of drug and disease targets; Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis; DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues.Results:A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins.Conclusion:Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.

ObjectiveTo study the correlation between the content of active ingredients of Aurantii Fructus in different main production areas and soil factors， so as to provide a theoretical basis for implementing ecological regulation of soil， improving the quality of Aurantii Fructus， and revealing the origin of genuine medicinal materials. MethodThe content of naringin， neohesperidin， total flavonoids， volatile oil， total nitrogen， total phosphorus， total potassium， and 17 soil factor-related indicators in 25 batches of Aurantii Fructus from different production areas were determined. The main soil factors affecting the content of active ingredients of Aurantii Fructus were analyzed by Pearson correlation analysis， principal component analysis， and grey correlation analysis. ResultThe pH value of the soil is between 4.83 and 8.21， and the soil is weakly acidic and neutral in general. Soil fertility exceeds the average. Pearson correlation analysis shows that the soil factors most related to the four active ingredients of Aurantii Fructus are total phosphorus， available copper， available zinc， exchangeable magnesium， available sulfur， available phosphorus， and available molybdenum. Principal component analysis shows that total nitrogen， alkali-hydrolyzable nitrogen， organic matter， available phosphorus， and available zinc are the main characteristic factors in soil. Grey correlation analysis shows that the main soil factors affecting the active ingredients of Aurantii Fructus are total phosphorus， total nitrogen， available zinc， available copper， exchangeable magnesium， and pH. ConclusionIn the cultivation of Aurantii Fructus， the medicinal material quality of Aurantii Fructus could be improved by adjusting the level of beneficial factors in the soil and improving the soil texture.

ObjectiveTo detect the flexibility differences of Plasmodium berghei K173 （PbK173）-infected red blood cells with varying degrees of sensitivity to artemisinin-based drugs and to preliminarily explore the underlying mechanisms of the differences. MethodA total of 102 specific-pathogen-free （SPF） male C57BL/6 mice were randomly divided into three groups， with 30 mice each in the control group and PbK173-resistant （PbK173-R） group， and 42 mice in the PbK173-sensitive （PbK173-S） group. Except for the control group， the rest groups were vaccinated with 1×10⁷ PbK173-S/PbK173-R infected red blood cells to establish a mouse malaria model. During the administration and recovery periods （control group， PbK173-R/PbK173-S）， dihydroartemisinin （DHA， 40 mg·kg^-1） and malaridine （MD， 6 mg·kg^-1） were administered continuously for four days. Peripheral blood was taken from the PbK173-S/PbK173-R groups with an infection rate equal to or greater than 20%. Peripheral blood and each organ were taken on the first day at the end of administration （dosing period） and on the fifth day at the end of administration （recovery period）， and blood parameters and organ indices of each group were examined. The osmotic fragility of peripheral blood red blood cells in each group was detected using the red blood cell osmotic fragility test. Western blot was applied to determine the levels of Piezo1 and Band3 proteins in the red blood cell membrane. ResultDuring the administration and recovery periods， there were no significant differences between the PbK173-S MD group and the DHA group. During the administration period， there were no significant differences in hematological parameters between PbK173-S and PbK173-R in the MD group. However， during the recovery period， the red blood cell count， hemoglobin concentration and hematocrit of the PbK173-R group were significantly higher than those of the PbK173-S group （P<0.05） in the MD group. Compared with that of the control group， the osmotic fragility of the PbK173-S/PbK173-R groups was significantly enhanced （P<0.01）， and the osmotic fragility of the PbK173-S group was significantly stronger than that of the PbK173-R group （P<0.01）. The osmotic fragility of red blood cells in the PbK173-S group during the administration period was significantly stronger than that in the control group and PbK173-R group during the administration period （P<0.01）. The osmotic fragility of red blood cells in the PbK173-R group during the recovery period was significantly higher than that in the control group during the administration period and the PbK173-S group during the recovery period （P<0.05）. Compared with those in the control group， the Piezo1 protein and Band3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced （P<0.01）. Compared with those in the PbK173-R group， the Piezo1 protein and Band 3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced. ConclusionThe flexibility of PbK173-infected red blood cells with different sensitivities to artemisinins differed. Plasmodium-infected red blood cells significantly reduced the levels of Piezo1 and Band3 proteins in the red blood cell membrane， and the erythrocyte flexibility exhibited a decreasing trend in the following order： normal group， PbK173-R group， and PbK173-S group.

Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Bronchial asthma （referred to as “asthma”） is a heterogeneous airway disease characterized by chronic airway inflammation and airway remodeling. Its pathogenesis is complex， the incidence is high and the disease is easy to repeat. Autophagy plays an important regulatory role in improving asthma symptoms. By regulating autophagy-related proteins and signaling pathways， the active components of traditional Chinese medicine （such as flavonoids， anthraquinones， terpenoids） and traditional Chinese medicine compounds （such as Wuhu decoction， Pingchuan granule， Sanzi yangqin decoction） can inhibit airway inflammatory response，reduce airway hyperresponsiveness，and alleviate airway remodeling，thus playing a role in the treatment of asthma. However， most of the current studies are basic studies，and the quality of evidence is not high．In the future，high-quality clinical and basic studies should be further carried out to fully demonstrate the scientific nature of traditional Chinese medicine in the treatment of asthma by regulating autophagy．

【Objective】 To investigate the factors influencing the length of hospital stays of the acute fatty liver of pregnancy (AFLP) patients, so as to establish the prediction model. 【Methods】 A total of 49 patients diagnosed as AFLP)in ShenZhen People’s Hospital between January 2008 and January 2023 were retrospectively analyzed. According to the median length of hospital stays, the patients were divided into two groups: Group A(n=21)and Group B(n=28). Preoperative general laboratory data, clinical features and postpartum adverse outcomes in both groups were analyzed. Multivariate binary logistic regression was used to analyze the independent factors affecting the length of hospital stays for AFLP, and a prediction model for hospitalization time was established. 【Results】 Comparison between Group B and Group A were as follows: hospital stays(d)(15.5 vs 8), preoperative icterus(%)[16(57.1%)vs 3(14.3%)], thrombin time(TT)(s)(24.2 vs 21.3), prothrombin time(PT)(s)(16.8 vs 15.3), activated partial thromboplastin time(APTT)(s)(52.3 vs 40.7), total bilirubin(TBIL)(μmol/L)(77.2 vs 45.2), indirect bilirubin(IBIL)(μmol/L)(21.2 vs 10), creatinine(Cre)(μmol/L)[(171.97±53.34) vs (131.81±45.06]), TT extension(%)[24(85.7%)vs 11(52.4%)], APTT extension(%)[27(96.4%)vs 7(33.3%)], IBIL elevation(%)[19(67.9%)vs 4(19%)], Cre concentration rise(%)[21(75%)vs 8(38%)], number of postpartum plasma exchange sessions(%)[23(82.1%)vs 5(23.8%)], postpregnancy co-infection phenomenon(%)[21(75%)vs 4(19%)], with Group B significantly higher than Group A. The preoperative platelet count(×10⁹/L)(128 vs 221)and the concentration of fibrinogen(g/L)[0.9 vs 1.6] in Group B were significantly lower than those in Group A. Univariate logistic regression analysis showed that preoperative icterus, postpregnancy co-infection phenomenon, number of postpartum plasma exchange sessions, preoperative TT extension, preoperative APTT extension, Cre concentration rise were influencing factors for the hospital stays of AFLP patients. According to the minimum result of Akaike information criterion, the multivariate binary logistic regression analysis (step-wise selection) showed that the number of postpartum plasma exchange sessions, icterus, preoperative APTT extension were the independent risk factor influencing the hospital stays of AFLP patients, and the logistic regression prediction model was established by incorporating the above three factors. Regularization techniques were further employed in linear regression to address and assess overfitting issues. Additionally, the confidence interval for the estimated effect sizes in each model have been acquired by bootstrapping techniques. 【Conclusion】 Preoperative icterus, preoperative APTT extension(APTT>43s)and the number of postpartum plasma exchange sessions were the independent risk factor influencing the hospital stays of AFLP patients and the logistic regression prediction model with high predictive effectiveness was established successfully.