Transdermal drug delivery offers advantages such as safety, convenience, and high patient compliance. However, the complex structure of the skin and significant individual variability, particularly the barrier function of the stratum corneum, result in generally low bioavailability for topical formulations. The formulation of topical drug products is complex, with numerous factors influencing quality, which requires strict control of product quality. Raman spectroscopy, as a non-destructive vibrational technique, combined with chemometric methods, imaging technology, and other spectroscopic techniques, can be applied to study the key quality attributes of topical drug formulations. The applications of Raman spectroscopy in studies of the crystal form, particle size distribution, excipient research, and in vitro transdermal experiments of topical drug formulations were summarized. In particular, it focused on the use of Raman spectroscopy in the selection of skin samples for in vitro permeation tests, the study of drug spatial distribution in the skin, and the interactions between drugs and the skin.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

Objective To analyze the epidemiological characteristics and disease burden of drug-resistant tuberculosis cases among elderly patients in Wuhan.Methods Clinical data of elderly pa-tients with pulmonary tuberculosis in Wuhan from January 2019 to December 2022 were retrospectively analyzed.Sputum samples were collected for Mycobacterium tuberculosis isolation,and drug suscepti-bility testing was performed using the proportion method.The epidemiological characteristics of drug-resistant tuberculosis and the direct economic burden of the patients were analyzed.Results A total of 972 elderly patients with positive Mycobacterium tuberculosis tests were included.The overall tuberculosis drug resistance rate was 21.19％(206/972).Male,rural residence,lower education level(primary school or below)and retreatment history significantly increased the risk of developing drug-resistant tu-berculosis(P＜0.05).The direct economic burden for elderly patients with drug-resistant tuberculosis was 24,101.52(8,283.98,39,598.89)RMB,and the indirect economic burden was 1,858.64(528.66,3,085.26)RMB.Conclusion The incidence of drug resistance in elderly tuberculosis is high,and male,rural residence,low education level and tuberculosis retreatment are the risk factors for drug resistance in elderly tuberculosis,and their economic burden is heavy after drug resistance.

ObjectiveThe full name of vertebroplasty is percutaneous vertebroplasty (PVP). It is a clinical technique that injects bone cement into the diseased vertebral body to achieve strengthening of the vertebra. The research on the safety and efficacy of bone cement is the basis for clinical application. In this study, vertebroplasty is used to evaluate and compare the safety and efficacy of Tecres and radiopaque bone cement in experimental pigs, and to determine the puncture method suitable for pigs and the pre-clinical evaluation method for the safety and efficacy of bone cement. MethodsTwenty-four experimental pigs (with a body weight of 60-80 kg) were randomly divided into an experimental group (Group A) and a control group (Group B). Group A was the Tecres bone cement group, and Group B was the radiopaque bone cement group, with 12 pigs in each group. Under the monitoring of a C-arm X-ray machine, the materials were implanted into the 1st lumbar vertebra (L1) and 4th lumbar vertebra (L4) of the pigs via percutaneous puncture using the unilateral pedicle approach. The animals were euthanized at 4 weeks and 26 weeks after the operation, respectively. The L4 vertebrae were taken for compressive strength testing, and the L1 vertebrae were taken for hard tissue pathological examination to observe the inflammatory response, bone necrosis, and degree of osseointegration at the implantation site. ResultsThe test results of compressive strength between groups A and B showed no significant difference at 4 weeks and 26 weeks after bone cement implantation (P > 0.05). Observation under an optical microscope (×100) revealed that at 4 weeks postoperatively, both groups A and B showed that the bone cement was surrounded by proliferative fibrous tissue, with lymphocyte infiltration around it. The bone cement was combined with bone tissue, the trabecular arrangement was disordered, and osteoblasts and a small amount of osteoid were formed. At 26 weeks postoperatively, bone cement was visible in both groups A and B. The new bone tissue was mineralized, the trabeculae were fused, the trabecular structure was regular and dense with good continuity, and no obvious inflammatory reaction was observed. ConclusionIn experimental pig vertebrae, there were no significant differences observed in the compressive strength, inflammation response, bone destruction, and integration with the bone between Tecres and non-radiopaque bone cement. Both exhibited good biocompatibility and osteogenic properties. It indicates that using vertebroplasty to evaluate the safety and efficacy of bone cement in pigs is scientifically sound.

Objective To analyze the factors influencing iodine nutritional status in pregnant women dur-ing pregnancy,based on thyroid function and thyroid autoantibody levels,and to explore the association between iodine nutritional abnormalities and pregnancy outcomes.Methods A total of 838 pregnant women who underwent routine prenatal checkups at Qinghai Provincial People's Hospital between January 2021 and June 2023 were pro-spectively enrolled in this study.All participants were followed until delivery.Seven cases were lost to follow-up,resulting in a final sample size of 831 participants.Among them,276 were in the first trimester,384 in the second trimester,and 171 in the third trimester.Data on urinary iodine concentration(UIC),urinary creatinine(UCr),thyroid function indicators,and thyroid autoantibodies were collected.Based on their iodine nutritional status,the participants were categorized into either the iodine-sufficient group or the iodine-abnormal group(including iodine-deficient,iodine-hyper-sufficient,and iodine-excessive subgroups).This study analyzed the iodine nutritional sta-tus of pregnant women during different gestational periods,compared thyroid function indices,prevalence of thy-roid diseases,and the positivity rates of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),and thyroid-stimulating hormone receptor antibody(TRAb)among different iodine status groups.Additionally,ad-verse pregnancy outcomes were compared across groups.Multivariate logistic regression analysis was conducted to identify risk factors associated with iodine abnormalities during pregnancy,and a predictive model was developed to assess its potential predictive value.Results Among the 831 pregnant women included in the study,373 cases(44.89％)exhibited iodine sufficiency,while 458 cases(55.11％)presented with iodine abnormalities,including 282 cases of iodine deficiency,144 cases of iodine hypersufficiency,and 32 cases of iodine excess.No statistically significant differences were observed in the iodine nutritional status across different trimesters(P>0.05).The se-rum level of thyroid-stimulating hormone(TSH)was significantly higher in the iodine abnormal group compared to the iodine sufficient group(P<0.05).Additionally,the iodine abnormal group demonstrated higher positivity rates of TPOAb alone,TGAb,and TRAb,as well as increased incidence of thyroid dysfunction and total adverse pregnancy outcomes compared to the iodine sufficient group(all P<0.05).These adverse indicators were also sig-nificantly elevated in the iodine-deficient,iodine super-sufficient,and iodine overdose subgroups compared to the iodine sufficient group(P<0.05).Elevated serum TSH levels and the presence of TPOAb,TGAb,and TRAb were identified as risk factors for iodine abnormalities during pregnancy(P<0.05).The predictive model con-structed for identifying iodine abnormalities in pregnant women demonstrated an area under the curve(AUC)of 0.876,with a sensitivity of 72.27％and a specificity of 89.01％.Conclusions The prevalence of iodine nutritional abnormalities among pregnant women during pregnancy was high,with most cases presenting iodine deficiency.These abnormalities were associated with thyroid function,thyroid autoimmunity,and pregnancy outcomes,but showed no significant correlation with gestational age.Furthermore,the prediction model developed based on iden-tified risk factors demonstrated effective performance in predicting iodine nutritional abnormalities during preg-nancy.

With the development of science and technology worldwide, the blooming of artificial intelligence (AI) and big data has brought new opportunities and challenges to the promotion of the research capacity of professional master's students in oncology. The construction of the new medical education in China aims to cultivate high-level medical talents with comprehensive multidisciplinary skills and innovative abilities to flexibly solve complex problems at the frontier of medicine. In this context, professional master's students in oncology, who are facing problems such as low scientific research output and uneven quality and needing improving scientific research literacy, have been required to develop into compound talents with both clinical and research prowess. To cultivate and promote the research capacity of professional master's students in oncology, the key steps include accelerating the construction of AI education and databases, highlighting the cultivation of their scientific research capacity, implementing and fostering the cultivation of innovative ability and scientific research thinking, piloting joint cultivation models by engineering universities and medical universities, emphasizing the construction of the curriculum and teacher team for oncology, piloting the multidisciplinary mode and COME mode, and establishing a multidisciplinary cooperation network.

AIM:To investigate the modulatory effects of electroacupuncture(EA)on spinal cord neurons au-tophagy in rats with bone cancer pain.METHODS:(1)Verification of autophagy-related protein expression at different time points in a bone cancer pain model:a total of 56 female Sprague-Dawley(SD)rats were randomly divided into a sham-operated(sham)group and a model group.The model group was further subdivided into 6 subgroups corresponding to time points of 3,6,9,12,15,and 18 d,with 8 rats per subgroup.Thermal and mechanical pain thresholds,tibial bone destruction,and spinal neuron marker neuronal nuclear antigen(NeuN)co-localized with LC3B,Beclin1,and P62 were examined in rats at each designated time point.(2)Changes in spinal autophagy proteins following EA intervention:an additional 40 rats were randomly assigned to sham group,model group,EA group,sham EA(SEA)group,and autoph-agy agonist rapamycin(Rap)group,with 8 animals per group.EA was administered to the rats in EA group beginning on day 6 after modeling,the rats in SEA group received needle insertion without electrical stimulation,while those in Rap group received intraperitoneal injections of rapamycin(5 mg/kg).Thermal pain thresholds were assessed at designated in-tervals,followed by mechanical pain threshold assessments conducted on the subsequent day.Treatment continued until day 21,with rapamycin administered at the end of each intervention day.Tibial bone destruction was evaluated using he-matoxylin-eosin(HE)staining.Expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 proteins in the spinal cord were determined by Western blot and immunohistochemistry.RESULTS:(1)Compared with the Sham group,thermal and mechanical pain thresholds were significantly decreased in the model group starting from day 6(P<0.01).Rat tibial bones exhibited notable damage,with severity progressively increasing over time.Protein expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 were significantly elevated in the spinal cord at various time points(P<0.01),and these pro-teins were co-localized with spinal cord neurons.(2)Compared with the model group,mechanical and thermal pain thresholds in the EA and Rap groups gradually increased,with statistically significant differences observed from days 8 and 6 onward,respectively(P<0.01).In addition,LC3B Ⅱ/LC3B I and Beclin1 protein expression levels were signifi-cantly upregulated(P<0.01),whereas P62 expression was markedly downregulated(P<0.01).Immunohistochemical analysis demonstrated significantly enhanced positive staining for LC3B Ⅱ/LC3B I and Beclin1 and significantly decreased positive staining for P62 in the spinal cord of rats in the EA and Rap groups(P<0.05).Notably,no significant differences were observed in the SEA group(P>0.05).CONCLUSION:EA promotes spinal cord neurons autophagy in rats with bone cancer pain.The enhancement of autophagy may represent a potential mechanism underlying the analgesic effect of EA in bone cancer pain.

Objective:To evaluate cerebrospinal fluid (CSF) flow dynamics and volume changes of pulsatile tinnitus (PT) patients induced by sigmoid sinus wall dehiscence (SSWD) using MRI.Methods:This was a cross-sectional study. Totally 55 SSWD-PT patients, and 35 age- and sex-matched healthy controls were prospectively enrolled at Beijing Tongren Hospital, Capital Medical University from October 2019 to September 2023. The CSF at the midbrain aqueduct level was analyzed based on phase-contrast MRI to obtain the flow dynamics information. Based on T 1-weighted turbo field echo sequence, the CSF was segmented and the volume of CSF was calculated using ITK-SNAP software. The Mann-Whitney U test was used to compare the differences of each parameter between the two groups. Binary logistic regression was used to analyze the parameters with statistically significant differences to obtain the independent influencing factors of SSWD-PT and establish the combined parameters. Receiver operating characteristic curve analysis was used to evaluate the efficacy of diagnosing SSWD-PT. Results:Compared with controls, the SSWD-PT group showed significantly decreased mean flux (MF), mean velocity, peak velocity( P<0.05), and significantly increased regurgitant fraction (RF), CSF volume ( P<0.05). No significant differences were observed in forward flow volume, backward flow volume, and stroke volume ( P>0.05). The logistic regression results showed that MF ( OR=0.497, 95% CI 0.305-0.808, P=0.005) and RF ( OR=1.809, 95% CI 1.040-3.147, P=0.036) were independent influencing factors of SSWD-PT. The area under the curve (AUC) of MF and RF for diagnosing SSWD-PT were 0.641 (95% CI 0.517-0.766) and 0.675 (95% CI 0.564-0.786), respectively. The AUC of the combination of MF and RF was 0.724 (95% CI 0.614-0.833). Conclusions:SSWD-PT patients have abnormal changes in CSF flow dynamics and volume. The MF and RF demonstrate moderate diagnostic value for diagnosing SSWD-PT.

Objective:To examine the distribution of pathogens that cause postoperative nosocomial infections in patients with rectal cancer(RC)and to construct a predictive nomogram for nosocomial infection.Methods:The clinical data of 1537 RC patients admitted to Sir Run Run Shaw Hospital between January 2021 and December 2022 were collected.Patients were assigned 1∶1 by propensity score matching(PSM)to the infection group(n=83)and control group(n=83)based on the occurrence of nosocomial infection.The dis-tribution and drug resistance of bacteria in patients with nosocomial infection were analyzed.Risk factors for postoperative nosocomial infection were identified by least absolute shrinkage and selection operator(LASSO)regression,and a predictive nomogram was con-structed using multivariate logistics regression.The predictive performance of the model was evaluated by receiver operating character-istic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results:A total of 93 strains of pathogens were isolated from the 83 infected patients,including 62 strains of Gram-negative bacteria(66.67%;predominantly Escherichia coli and Pseudomonas ae-ruginosa),25 strains of Gram-positive bacteria(26.88%;mainly Enterococcus faecalis),and 6 strains of fungi(6.45%;all Candida albicans).LASSO and multivariate logistics regression showed that smoking(odds ratio[OR]=3.97,95%CI=1.27-12.43),the dwelling time of drainage tube(OR=1.19,95%CI=1.08-1.30),difference in preoperative and postoperative neutrophil counts(OR=1.23,95%CI=1.01-1.49),and difference between preoperative and postoperative C-reactive protein levels(OR=1.05,95%CI=1.03-1.07)were inde-pendent risk factors for postoperative nosocomial infection in RC patients.The area under the ROC curve of the nomogram constructed based on the above factors was 0.933(95%CI=0.896-0.969).The calibration curve showed that the predicted risk was in good agree-ment with the actual observed risk of infection.In addition,DCA demonstrated that the nomogram has good clinical utility and high net clinical benefits in predicting nosocomial infection.Conclusion:The nomogram constructed in this study has a good predictive perfor-mance in postoperative nosocomial infection in RC patients.