OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objective: To investigate the self-monitoring blood pressure behavior and its influencing factors among residents in Jiangsu Province, so as to provide the basis for strengthening proactive blood pressure monitoring among residents. Methods: Permanent residents aged 35-75 years in six counties (cities, districts), Jiangsu Province, were selected using the stratified cluster sampling method in 2023. Data on basic information, disease history, and self-monitoring blood pressure behavior were collected, height and weight were measured to calculate the body mass index (BMI); and blood glucose and lipid levels were measured. Self-monitoring blood pressure behavior was defined as having measured blood pressure at least once in the past three months. Factors affecting self-monitoring blood pressure behavior were identified using a multivariable logistic regression model. Results: A total of 12 475 residents were surveyed, including 5 748 males and 6 727 females, with a male-to-female ratio of 1∶1.17. There were 3 855 residents aged 45-<55 years (30.90%) and 5 511 residents who had self-monitoring blood pressure behaviors (44.18%). Multivariable logistic regression analysis showed that the residents who were males (OR=1.167, 95%CI: 1.081-1.261), lived in rural areas (OR=1.430, 95%CI: 1.321-1.547), aged 45-75 years (45-<55 years, OR=1.384, 95%CI: 1.241-1.543; 55-<65 years, OR=1.397, 95%CI: 1.243-1.570; 65-75 years, OR=1.196, 95%CI: 1.049-1.363), had an annual household income ≥30 000 yuan (30 000-<60 000 yuan, OR=1.190, 95%CI: 1.072-1.321; 60 000-<110 000 yuan, OR=1.330, 95%CI: 1.191-1.485; ≥110 000 yuan, OR=1.746, 95%CI: 1.536-1.984), were overweight (OR=1.170, 95%CI: 1.070-1.280) or obese (OR=1.248, 95%CI: 1.120-1.391), were unaware (OR=1.221, 95%CI: 1.103-1.353) or aware (OR=3.937, 95%CI: 3.575-4.335) of having hypertension, were aware of having diabetes (OR=1.538, 95%CI: 1.354-1.749), and aware of having dyslipidemia (OR=1.265, 95%CI: 1.106-1.447) were more likely to have self-monitoring blood pressure behaviors. Conclusions Among the residents aged 35-75 years in Jiangsu Province, 44.18% had self-monitoring blood pressure behavior. Gender, place of residence, age, annual household income, BMI, hypertension, diabetes, and dyslipidemia were identified as influencing factors for self-monitoring blood pressure behavior.

Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings， it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia （PSD）. In clinical practice， treatment is tailored according to the location of PSD. During the oral stage， when the pathogen invades the face and mouth， resulting in excessive salivation， acupoints are primarily selected from the foot shaoyin （少阴） kidney channel， in combination with ren mai （任脉） ， du mai （督脉）， chong mai （冲脉） and the spleen channel， to replenish essence and fill the marrow， dispel dampness and unblock the channels. In the pharyngeal stage， as the pathogen obstructs the throat， disrupting normal swallowing， the therapy emphasizes dredging the shaoyang （少阳） channel and warming and tonifying the jueyin （厥阴） channel， by taking acupoints mainly from the hand and foot shaoyang channels， along with the jueyin channels， so as to soothe the liver and promote bile secretion， regulate and harmonize qi and blood. During the esophageal stage， where the pathogen damages the esophagus， impeding food passage， the treatment emphasizes activating the yangming （阳明） channels and regulating taiyin （太阴） channels； acupoints are mainly selected from the foot yangming stomach channel， along with the taiyin channels， aiming to warm yang， unblock the channels and dispel stasis.

OBJECTIVE: To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region. METHODS: 268 infants presented at the Women and Children's Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017). RESULTS: Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). CONCLUSION WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.
Humans ; Exome Sequencing/methods* ; Infant ; Female ; Male ; Infant, Newborn ; Genetic Diseases, Inborn/diagnosis* ; Genetic Testing/methods*

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ). METHODS: A child with OFDSⅠ who received treatment at the Women and Children's Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children's Hospital (Ethic No.: EC 2024-063). RESULTS: The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c.710dup (p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child's parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS4_Moderate+PM2-Supporting+PM6_Supporting+PP4). CONCLUSION Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c.710dup (p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
Humans ; Female ; Orofaciodigital Syndromes/genetics* ; Exome Sequencing ; Retrospective Studies ; Mutation ; Child ; Proteins

OBJECTIVE: To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL). METHODS: A child who was admitted to Ningbo Women and Children's Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063). RESULTS: Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. CONCLUSION For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.
Child, Preschool ; Humans ; DNA Copy Number Variations/genetics* ; Down Syndrome/genetics* ; GATA1 Transcription Factor/genetics* ; Leukemia/congenital* ; Mosaicism ; Mutation ; Retrospective Studies ; Whole Genome Sequencing

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.

AIM:This study aims to design pH/near-infrared(NIR)dual-responsive metal-organic framework composite nanoparticles co-loaded with indocyanine green(ICG)and sphingosine kinase 1(SphK1)siRNA(siSphK1),and to evaluate their anticancer efficacy against non-small-cell lung cancer A549 cells.METHODS:The ZIF-8 nanopar-ticles were synthesized and loaded with ICG and siSphK1 to prepare ZIF-8@ICG@siSphK1 nanoparticles.Their morpholo-gy,particle size,surface charge,and crystalline structure were characterized through transmission electron microscopy,dynamic light scattering,and X-ray diffraction.Stability,siSphK1 encapsulation and protection,and pH/NIR response were assessed.The gene silencing efficacy and anticancer activity in A549 cells were evaluated using Western blot,RT-qPCR,MTT assay,flow cytometry,and reactive oxygen species(ROS)fluorescence staining.RESULTS:The ZIF-8@ICG@siSphK1 nanoparticles exhibited a typical polyhedral structure with an average particle size of(76.8±0.9)nm and a ζ potential of(9.2±0.1)mV.The nanoparticles effectively encapsulated siSphK1,protecting it from RNase degra-dation,and demonstrated excellent NIR responsiveness with a photothermal conversion efficiency of 39.7%.After 10 h of 808 nm laser irradiation,siRNA cumulative release was significantly higher at pH 5.5 compared with pH 7.4.In A549 cells,the nanoparticles efficiently delivered siSphK1 under NIR irradiation,significantly down-regulated SphK1 gene ex-pression,inhibited cell proliferation,induced apoptosis,and increased intracellular ROS levels.CONCLUSION:The ZIF-8@ICG@siSphK1 nanoparticles effectively induce cytotoxic effects against A549 cells through gene silencing and pho-tothermal therapy.

Objective To investigate the effects of Gandou Fumu Decoction on liver fibrosis,iron metabolism,and ferroptosis in patients with hepatolenticular degeneration(Wilson disease,WD).Methods Seventy-eight hospitalized patients with WD characterized by kidney and liver deficiency,with phlegm and blood stasis,from the Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,were randomly assigned to two groups using a random number table method.The control group(n=39)received sodium dimercaptosulfonate in combination with a low-copper and high-protein diet.The observation group(n=39)received the same treatment as the control group,with the addition of Gandou Fumu Decoction(one dose per day,taken twice daily,in the morning and evening).Both groups underwent six treatment cycles,each lasting eight days.Ultrasonographic parameters,including portal vein main trunk diameter(PVMD),portal vein velocity(PVV),shear wave velocity(SWV),liver stiffness measurement(LSM),serum liver fibrosis markers(hyaluronic acid[HA],laminin[LN],procollagen typeⅢN-terminal peptide[PⅢNP],collagen type Ⅳ[CⅣ],aspartate aminotransferase to platelet ratio index[APRI],fibrosis-4 index[FIB-4]),and iron metabolism indicators(serum iron[SI],ferritin[FT])were compared before and after treatment.The relationship between baseline iron metabolism markers and ultrasonographic parameters,as well as serum liver fibrosis markers,was analyzed.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,and adverse reactions were also compared between the groups.Additionally,bioinformatics analysis was performed to identify potential targets of Gandou Fumu Decoction for WD treatment.Peripheral blood mononuclear cells were collected from a normal group of 20 healthy individuals,as well as from both the control and observation groups before and after treatment.Real time fluorogenic quantitative PCR was performed to validate the expression changes of these targets across the groups.Results Compared with pre-treatment values,no significant changes were observed in PVMD levels in either group after treatment.No significant change in PVV was observed in the control group,whereas a significant decrease was noted in the observation group(P＜0.01).SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels were significantly reduced compared to pre-treatment levels(P＜0.05,P＜0.01),whereas SI remained unchanged.Compared with the control group,the observation group had no significant difference in PVMD but had significantly lower PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels(P＜0.05,P＜0.01),whereas SI remained unchanged.The total effective rate of treatment in the observation group was significantly higher than that in the control group(P＜0.05).Both groups showed a significant reduction in TCM syndrome scores after treatment(P＜0.01),with a significantly greater reduction observed in the observation group(P＜0.01).No significant adverse reactions were reported during treatment.Before treatment,there was no significant correlation between the SI of both groups and PVMD,PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,and FIB-4.In the observation group,FT showed a positive correlation with SWV,LSM,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.05,P＜0.01),while in the control group,FT showed a positive correlation with HA,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.01).After treatment,in the control group,SI showed a positive correlation with APRI and FIB-4(P＜0.05,P＜0.01),but there was no significant correlation between SI in the observation group and FT in both groups with the above-mentioned indicators.Bioinformatics analysis identified four potential targets of Gandou Fumu Decoction for treating WD,namely heme oxygenase 1(HMOX1),peroxisome proliferator-activated receptor alpha(PPARα),small heat shock protein B1(HSPB1),and mitogen-activated protein kinase 3(MAPK3).Compared to the normal group,both the control and observation groups had significantly lower PPARαand HSPB1 expression and significantly higher HMOX1 and MAPK3 expression before treatment(P＜0.01).Compared to before treatment within the same group,both groups showed significantly increased PPARα and HSPB1 expression and significantly decreased HMOX1 and MAPK3 expression after treatment(P＜0.05,P＜0.01).After treatment,the observation group had significantly higher PPARα and HSPB1 expression and lower HMOX1 and MAPK3 expression than the control group(P＜0.05,P＜0.01).Conclusion Gandou Fumu Decoction demonstrates remarkable advantages in improving clinical efficacy,Chinese medicine syndrome scores,iron metabolism,liver fibrosis progression,ultrasound imaging parameters,and ferroptosis-related biomarkers expression in patients with WD,with a favorable safety profile.