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 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.

Objective To investigate the influence of auricular acupressure combined with repetitive transcranial magnetic stimulation(rTMS)on swallowing function and neurological function in stroke pa-tients.Methods A total of 120 patients with dysphagia after stroke admitted to the hospital from January 2022 to June 2023 were selected as the research objects and divided into the control group,the auricular acu-pressure group,the rTMS group and the combined group according to the random number table method,with 30 cases in each group.The control group received routine care,the auricular acupressure group received auric-ular acupressure treatment on the basis of the control group,while the rTMS group received rTMS treatment,and the combined group received both auricular acupressure and rTMS treatment.All interventions lasted 4 weeks.Swallowing function was assessed before and after treatment using Functional Oral Intake Scale(FOIS),modified Mann Assessment of Swallowing Ability(MASA),and Water Swallow Test.Swallowing-related quality of life was evaluated before and after treatment by the Swallowing Quality of Life(SWAL-QOL)questionnaire.Neurological impairment was assessed before and after treatment using National Institu-tes of Health Stroke Scale(NIHSS).Results After treatment,FOIS and MASA scores in the four groups were higher than those before treatment,with the auricular acupressure group and the rTMS group showing higher scores than the control group,and the combination group significantly higher than the other three groups(P<0.05).The overall effectiveness rate for swallowing function in the combination group was 93.33%,significantly higher than 60.00%in the control group,63.33%in the auricular acupressure group,and 73.33%in the rTMS group(P<0.05),while there was no significant difference among the other three groups(P>0.05).After treatment,SWAL-QOL scores in the four groups were higher than that before treat-ment,with the auricular acupressure group and the rTMS group showing higher scores than the control group,and the combination group significantly higher than the other three groups(P<0.05).After treat-ment,NIHSS scores in the four groups were lower than that before treatment,and the combination group had significantly lower scores compared to the other three groups(P<0.05).Conclusion Auricular acupressure combined with rTMS could improve swallowing function and quality of life,and promote neurological function recovery in stroke patients.

OBJECTIVE To evaluate cerebrospinal fluid(CSF)flow dynamics and volume changes of pulsatile tinnitus(PT)patients caused by sigmoid sinus wall dehiscence(SSWD)with different intracranial pressure via MRI.METHODS Prospective enrolled 35 SSWD-PT patients with intracranial hypertension,25 SSWD-PT patients with normal intracranial pressure and 35 age-,sex-matched healthy controls.Demographic characteristics were recorded.Intracranial pressure was assessed by the index of transverse sinus stenosis(ITSS)and morphology changes.CSF flow dynamics were evaluated via phase-contrast magnetic resonance imaging(PC-MRI)and CSF volume were evaluated via three-dimensional T1-weighted turbo field echo(3D T1-TFE)sequence and ITK-SNAP software.Compared the differences of each index between three groups.RESULTS The mean flux and regurgitant fraction were significantly different among the three groups(P<0.05).The intracranial hypertension group presented significantly decreased mean flux(MF)and significantly increased regurgitant fraction(RF)compared to controls(P<0.017).There were no significant differences in MF and RF of normal intracranial pressure group compared with intracranial hypertension group and control group(P>0.017).There were no statistical differences in age,sex,body mass index,forward flow volume,backward flow volume,mean velocity,peak velocity,stroke volume and CSF volume(P>0.05).CONCLUSION SSW D-PT patients have abnormal changes in CSF,and those with increased intracranial pressure are more obvious.These changes may be associated with abnormal hemodynamics in the sigmoid sinus and the occurrence of PT.

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 epidemiological characteristics and trends of preterm births in China using medical institution survey data, thereby providing epidemiological data support for perinatal care.Methods:Based on a nationwide sampling survey on healthcare quality data from 2017 to 2022, this study included 3 547, 4 436, 4 513, 4 535, 5 068, and 5 790 medical institutions, with 7 039 107, 8 926 441, 9 006 420, 7 051 984, 7 311 862, and 7 354 062 parturient women, respectively. The overall rates of preterm birth (live births at 28 to 36 +6 weeks of gestation/overall live births) and early preterm birth (live births at 28 to <34 weeks of gestation/overall live births) were calculated at the national level, across diverse provinces, autonomous regions, municipalities and Xinjiang Production and Construction Corps, and for various levels of medical institutions. Generalized estimating equations were used to analyze the influence of maternal characteristics and medical institution characteristics on the rates of preterm birth and early preterm birth. Results:From 2017 to 2022, both the preterm birth rate and the early preterm birth rate in China showed a continuous increase. The preterm birth rate rose from 5.13% (363 036/7 079 454) in 2017 to 6.56% (487 150/7 424 734) in 2022, and the early preterm birth rate increased from 1.32% (118 021/8 971 870) in 2018 to 1.43% (106 157/7 424 734) in 2022. These rates showed an overall increasing trend in private, secondary public specialty, and general hospitals. In tertiary public specialty hospitals, these rates fluctuated around 8.0% and 2.0% from the year 2018, respectively, while in tertiary public general hospitals, these rates peaked in 2020 at 8.63% (205 570/2 381 523) and 2.19% (52 197/2 381 523), respectively. Compared with 2017, by 2022, the preterm birth rate had increased to varying degrees in all provinces, autonomous regions, municipalities and Xinjiang Production and Construction Corps, except for Henan Province [preterm birth rate in 2017 was 6.22% (27 173/437 187); preterm birth rate in 2022 was 5.83% (37 604/645 104)]. As for the early preterm birth rate, it showed a decline in Fujian, Guangdong, Guangxi, Hainan, Henan, Jiangsu, Shanghai, Xinjiang, Yunnan, and Zhejiang, but had increased to varying degrees in all other provinces , autonomous regions, municipalities and Xinjiang Production and Construction Corps across the country. The grade and location of medical institutions both had a significant impact on the preterm birth rate and early preterm birth rate (both P<0.05). For every 1% increase in the proportions of multiparous women, women of advanced maternal age, or twin pregnancies, the preterm birth rate increased by 0.014%, 0.042%, and 0.763%, and the early preterm birth rate increased by 0.004%, 0.013%, and 0.239%, respectively (all P<0.05). Conclusion:From 2017 to 2022, the preterm birth rate and early preterm birth rate in China have continued to rise, reflecting the dual challenges of changing characteristics in the childbearing population and the uneven distribution of medical and health resources faced by maternal and child healthcare in China.

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.

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.