OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Objective To develop and validate a risk prediction model based on early platelet-related parameters for bronchopulmonary dysplasia(BPD)in neonates admitted to the neonatal intensive care unit(NICU),and to facilitate early identification and intervention in high-risk populations.Methods Clinical data of 291 preterm infants with a gestational age(GA)≤32 weeks or a birth weight(BW)＜1 500 g,admitted to the NICU,were retrospectively analyzed.Out of these,214 cases were selected as the modeling group.This group was further categorized into the BPD group(n=76)and the non-BPD group(n=138),based on whether they required oxygen therapy at 28 days post-birth.Perinatal data,platelet-related parameters and other indicators between the two groups.Univariate and multivariate Logistic regression analyses were conducted to identify BPD risk factors,followed by the construction of a nomogram.An additional cohort of 105 preterm infants with GA≤32 weeks or BW＜1 500 g,were used to validate the model.This cohort was divided into the BPD group(n=43)and the non-BPD(n=62)group.Receiver operating characteristic(ROC)curve and calibration curve were used to internally verify the efficiency of the prediction model.Results The Logistic regression analysis identified GA,BW,Apgar score at 5 minutes≤7,invasive ventilation,platelet count(PLT)and mean platelet volume(MPV)as significant factors in the model(P＜0.05).The constructed nomogram was formulated using R language,and the areas under the ROC curve(AUC)for the three models were 0.908,0.931 and 0.918,respectively(P＜0.05).The verification group was verified by Bootstrap.The calibration curve showed a good fit.The internal validation AUC values of the three models were 0.877,0.890 and 0.886,respectively.Conclusion GA,BW,invasive ventilation,Apgar score at 5 minutes≤7,MPV and PLT are key risk factors for BPD onset.The risk prediction model based on these indicators can effectively predict BPD,providing clinicians with a valuable tool for early detection and intervention in the development of BPD.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective To observe the clinical efficacy and safety of ticagrelor tablets combined with atorvastatin calcium tablets in the treatment of cerebral thrombosis.Methods The patients with cerebral thrombosis were divided into control group and treatment group according to cohort methods.Two groups were given basic therapy.On the basic therapy,control group was given atorvastatin calcium 20 mg per time,once a day,orally;on the basic of control group,the treatment group received ticagrelor 90 mg per time,twice a day,orally.Two groups were treated for 4 months.The clinical efficacy,nerve function,blood viscosity,platelet parameters,brain injury markers and adverse drug reactions were compared between two groups.Results Treatment and control groups enrolled 119 and 117 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.60％(109 cases/119 cases)and 82.05％(96 cases/117 cases)with significant difference(P＜0.05).After treatment,the scale scores of treatment and control groups were(5.47±0.82)and(6.51±0.96)points;the plasma viscosity levels were(1.35±0.21)and(1.62±0.24)mPa·s,whole blood high shear viscosity levels were(3.67±0.51)and(4.01±0.59)mPa·s;the whole blood low shear viscosity levels were(6.12±0.93)and(7.05±1.07)mPa·s;the platelet adhesion rates were(30.52±3.81)％and(36.21±4.02)％;the mean platelet volumes were(12.75±1.86)and(15.42±2.06)fL;the carboxy-terminal hydrolase of ubiquitin levels were(0.39±0.06)and(0.51±0.07)μg·L-1;the key protein antigen-5 of aging levels were(90.76±12.23)and(81.64±11.95)μg·L-1;and the differences were statistically significant between two groups(all P＜0.05).The adverse drug reactions of two groups were nausea,vomiting,bleeding,abdominal pain and diarrhea.The total incidences of adverse drug reactions in treatment and control groups were 5.04％and 4.27％,without significant difference(P＞0.05).Conclusion Ticagrelor tablets combined with atorvastat in calcium tablets have a significant clinical efficacy in the treatment of patients with cerebral thrombus,which can significantly improve the neurological function,blood viscosity,brain injury markers,and platelet parameters of patients,without increasing the incidence of adverse drug reactions.

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS). Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of 151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cfPWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling. Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2 rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a 19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Objective:To investigate the risk factors for severe distal curve progression after posterior hemivertebra (HV) resection and short-segment fixation in patients with congenital cervicothoracic scoliosis (CTS), and to analyze the surgical revision strategy.Methods:Imaging and clinical data of patients who underwent posterior HV resection and short-segment fixation for CTS between August 2012 and August 2021 at Nanjing Drum Tower Hospital were retrospectively analyzed. A total of 55 patients were recruited, including 27 females and 28 males with an average age of 8.5±3.6 years (range 3-15 years) at surgery and an average Risser grade of 0.7±1.4 (range 0-4). The number of fused segments averaged 6.9±1.6 (range 4-10), and the mean follow-up was 38.7±18.9 months (range 9-94 months). According to the severity of distal curve progression, the recruited patients were divided into three groups: non-progression group (NPG), mild progression group (MPG), and severe progression group (SPG). The latter two groups were collectively called the progression group (PG). The cervicothoracic Cobb angle, T1 tilt angle, coronal balance distance (CBD), neck tilt angle, clavicular angle, head tilt angle, head shift, and upper (UIV) and lower instrument vertebra (LIV) tilt angle on the standing whole spine X-ray were measured before and after surgery and at the last follow-up. The correction rate of the Cobb angle in the osteotomy area was measured and calculated on CT three-dimensional reconstruction, and the proportion of patients with Klippel-Feil syndrome (KFS) was recorded. Statistical analysis was conducted on the various parameters between the two groups. For factors with statistical significance in the single-factor analysis, binary logistic regression analysis was performed to identify the high-risk factors for distal curve progression.Results:There were 38 cases in the NPG, 11 in the MPG, and 6 in the SPG. Compared to the NPG, the PG showed more severe coronal imbalance preoperatively, with CBD of 35.6±22.3 mm and 11.6±7.1 mm respectively; more severe neck tilt and head shift, with neck tilt angle of 17.4°±8.3° and 12.4°±6.9° respectively, and head shift of 22.8±17.7 mm and 13.9±9.8 mm respectively; and a higher proportion of KFS, 65% (11/17) and 34% (13/38) respectively, all with statistical significance ( P<0.05). Postoperatively, the PG showed more severe coronal imbalance compared with the NPG, with 17.3±12.7 mm and 9.6±8.1 mm respectively; more evident residual deformity, with cervical tilt angles of 9.4°±4.6° and 6.4°±5.3° respectively, and head shift of 14.7±7.4 mm and 9.1±5.9 mm respectively; lower correction of Cobb angle in the apical osteotomy region, with rates of 40.1%±15.2% and 50.3%±19.9% respectively; more significant UIV and LIV tilt, with UIV tilt angles of 14.3°±7.4° and 9.8°±5.3° respectively, and LIV tilt angles of 8.1°±5.5° and 4.5°±3.6° respectively, all with statistical significance ( P<0.05). SPG showed only more severe coronal imbalance preoperatively compared with the MPG, with 50.7±31.3 mm and 27.3±9.6 mm respectively; and head shift, with 33.5±25.0 mm and 16.9±11.0 mm respectively, all with statistical significance ( P<0.05). Logistic regression analysis demonstrated a significant correlation between significant preoperative coronal imbalance and postoperative distal scoliosis progression [ OR=1.299, 95% CI (1.101, 1.531), P=0.002]. Five cases (83.3%) in SPG underwent revision surgery with an average follow-up of 25 months, and selecting the LIV down to the stable region was the major revision strategy. Conclusion:Combined KFS, residual cervicothoracic deformities, and tilting of UIV and LIV are key causes, whereas significant preoperative coronal imbalance is an independent risk factor predisposing to the distal curve progression.

Objective:To compare the clinical outcomes between three-column osteotomy and posterior-column osteotomy for correcting dystrophic kyphoscoliosis secondary to neurofibromatosis type 1 (DKS-NF1).Methods:ALL of 84 patients with DKS-NF1 were retrospectively analyzed, and the average age was 17.7±6.9 years. There were 50 cases with single curve, 18 cases with double curves, and 16 cases with triple curves; kyphosis was found in 42 cases in the thoracic area, 31 cases in the thoracolumbar area, and 11 cases in the lumbar area. The patients were divided into two groups: posterior column osteotomy group and three column osteotomy group based on surgical strategy. The radiographic parameters (including the magnitude of kyphosis, scoliosis, coronal balance distance, etc.) were compared between the two groups before and after surgery, and during the follow-up. The surgical efficacy was also compared based on the spinal correction and complications (such as cerebrospinal fluid leakage, pneumothorax, rod breakage, etc.).Results:The posterior column osteotomy group consisted of 74 patients and the column osteotomy group consisted of 10 patients. The age of patients in the posterior column osteotomy group was significantly younger than that in the three-column osteotomy group (15.8±4.8 years vs. 29.4±10.2 years, t=7.088, P<0.001), and the proportion of preoperative traction in this group was significantly higher than that in the three column osteotomy group (26/74 vs. 0, P=0.027). The apex of kyphosis in the three-column osteotomy group mainly located in the thoracolumbar and lumbar area, significantly higher than that in the posterior column osteotomy group (10/10 vs. 32/74, P=0.001). The magnitude of kyphosis in the two groups were 73.8°±20.9° and 63.1°±21.4° before surgery, respectively ( t=1.506, P=0.136). After surgery, they were corrected to 43.1°±20.9° and 21.1°±22.8°, respectively ( t=3.066, P=0.003), with correction rates of 43.7% ±19.6% and 84.1% ±78.7%, respectively ( t=3.677, P<0.001). At the last follow-up, they were maintained at 46.5°±20.9° and 24.6°±25.5°, respectively ( t=3.016, P=0.003). The Cobb angle of the main curve was corrected from preoperative 83.0°±29.0° and 66.3°±17.7° ( t=1.766, P=0.081) to postoperative 50.6°±20.8° and 40.8°±15.6° ( t=1.436, P=0.155), with correction rates of 38.3% ±16.6% and 39.3% ±12.7% ( t=0.191, P=0.849), respectively. At the last follow-up, they were maintained at 52.3°±20.5° and 43.1°±18.2°, respectively ( t=1.339, P=0.185). The proportion of multi-rod system application and screw density in three column osteotomy group was significantly higher than that in posterior column osteotomy group (8/10 vs. 20/74, P=0.002; 72.0% ±11.3% vs. 61.4% ±14.6%, t=2.173, P=0.033). The incidence of complications in the two groups was 12.2% (posterior column osteotomy group, 9/74) and 20% (three column osteotomy group, 2/10), respectively, with no statistically significant difference ( P=0.613). Conclusion:Three-column osteotomy is mainly used to treat adult kyphosis in DKS-NF1 patients. While the posterior column osteotomy methods were mainly applied in young patients. Most patients can achieve the purpose of deformity correction by posterior column osteotomy alone or combined with anterior complementary fusion. For patients with severe kyphosis, preoperative Halo gravity traction can help to further correct the intraoperative deformities.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.