Objective To establish a central cutting two-dimensional liquid chromatography for the determination of lamotrigine in human plasma. Methods External standard method was used. The first dimensional chromatographic column: SNCB（T）-1A（silica gel, 4.6 mm×50 mm, 5 μm）, mobile phase A:VCV-1D mobile phase, flow rate: 0.4 ml/min; mobile phase B: water, flow rate: 1.0 ml/min; second dimensional chromatographic column: Symmetry C₁₈ （4.6 mm×250 mm, 5 μm）, mobile phase: acetonitrile-10 mmol/L ammonium acetate solution（V/V=25∶75）, flow rate: 1.0 ml/min；Intermediate column: SBX 4-MA（resin, 3.0 mm×10 mm, 5µm）. The UV detection wavelength：306 nm, the column temperature：45 ℃, and the injection volume：200 μl. Results The linear range of lamotrigine was 1.24-39.50 μg/ml, the lower limit of quantification was 1.24 μg/ml, the detection limit was 0.02 μg/ml, the intra-day precision RSD was less than 5%, the day-to-day precision RSD was less than 10%, the variation of intra-day accuracy ranged from 102.17% to 111.17%, and the daytime accuracy variation ranged from 99.80% to 107.31% the recovery RSD was less than 5%, and the variation range was 89.95% -96.16%. After 24 hours storage at room temperature, repeated freezing and thawing for 3 times and storage at −40 ℃ for 2 weeks, the ratio of the measured value/labeled value ranged from 87.01% to 115.88%. Conclusion In this study, a method with simple operation, good stability, high sensitivity and good reproducibility was established, which could be suitable for clinical monitoring of blood concentration of lamotrigine and provide reliable monitoring data support for clinical individualized medication guidance.

Objective:To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. Methods:Four patients diagnosed with PMS at Guangzhou Women and Children′s Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Guangzhou Women′s and Children′s Medical Center Liuzhou Hospital (Ethics No. 2025-007).Results:All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 kb to 112.64 kb, primarily involving the SHANK3 gene. Conclusion:PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.

Objective:To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. Methods:Four patients diagnosed with PMS at Guangzhou Women and Children′s Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Guangzhou Women′s and Children′s Medical Center Liuzhou Hospital (Ethics No. 2025-007).Results:All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 kb to 112.64 kb, primarily involving the SHANK3 gene. Conclusion:PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.

Objective To investigate the quality and in vitro release behavior of the sirolimus self-microemulsion-mesoporous silicon sustained release tablets and provide a basis for further research and development of related preparations. Methods The hardness, brittleness and content uniformity of the sustained-release tablets were tested refer to Pharmacopoeia of the People’s Republic of China 2020. Different diameters （10, 11, 12 mm）, different hardness （50, 70, 90 N）, different speed （50, 75, 100 r/min）, different dissolution methods （pulp method, basket method） were investigated. The release conditions of the sustained-release tablets with different pH solution （distilled water solution and 0.4% SDS solution with pH of 1.2, 4.5 and 6.8, respectively） and the in vitro release conditions of the sustained-release tablets were observed. Results The hardness, brittleness and content uniformity of the self-made sustained-release tablets were qualified; different diameters and dissolution methods had no effect on the drug release behavior of the sustained-release tablets in vitro, while the different hardness, different rotational speed and the different pH release media had certain effects. Conclusion The sirolimus self-microemulsion-mesoporous silicon sustained release tablets had good sustained-release effect in vitro and was deserved to further study.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. METHODS: Four patients diagnosed with PMS at Guangzhou Women and Children's Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Hospital (Ethics No. 2025-007). RESULTS: All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 Kb to 112.64 Kb, primarily involving the SHANK3 gene. CONCLUSION PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.
Child ; Humans ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Exome Sequencing ; Nerve Tissue Proteins/genetics* ; Phenotype

Objective To analyze the correlation between the drug resistance rate of common pathogens in blood culture of inpatients from the First Hospital Affiliated to Hebei North University from 2019 to 2021 and the frequency of antimicrobial drug use (DDDs). Methods Strains isolated from positive blood cultures of inpatients from 2019 to 2021 were collected, and data on antimicrobial drug use in patients with positive blood cultures during the same period were also collected. WHONET 5.6 software and Pearson correlation analysis were used to explore the correlation between pathogenic bacterial resistance rate and antimicrobial DDDs. Results A total of 916 samples tested positive in blood cultures from 2019 to 2021. Among the top antimicrobial drugs in DDDs, the DDDs of cefazolin, cefuroxime, and ceftazidime all showed an upward trend year by year (the increase from 2019 to 2021 was 38.8%, 228.3%, and 87.1%, respectively). A total of 739 pathogenic bacteria strains were isolated from positive blood culture samples from 2019 to 2021, and the top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa, accounting for 37.2%, 16.1%, 8.1%, 7.4%, and 6.5%, respectively. The drug resistance rates of Escherichia coli to cefazolin, ceftazidime, cefotaxime, and polymyxin B were positively correlated with their DDDs (r=0.961, 0.907, 0.988, 0.997, P < 0.05). The drug resistance rates of Klebsiella pneumoniae to piperacillin, cefazolin, cefotaxime, cefepime, aztreonam, imipenem, meropenem, levofloxacin, and polymyxin B were positively correlated with their DDDs (r=0.766, 0.772, 0.838, 0.667, 0.734, 0.821, 0.904, 0.980, 0.997, P < 0.05). The drug resistance rate of Pseudomonas aeruginosa to gentamicin was positively correlated with their DDDs (r=0.878, P < 0.05). The drug resistance rate of Acinetobacter baumannii to moxifloxacin was positively correlated with its DDDs (r=0.856, P < 0.05). However, there was no correlation between the drug resistance rates of Staphylococcus aureus and Staphylococcus epidermidis to most commonly used antimicrobial drugs and antimicrobial DDDs (P>0.05). Conclusion The pathogenic bacteria causing bloodstream infections in inpatients at the First Hospital Affiliated to Hebei North University from 2019 to 2021 are complex and diverse (mainly Gram-negative bacteria). The overall drug resistance rate of pathogenic bacteria shows an upward trend, and there is a correlation between the drug resistance rates of most pathogenic bacteria and antimicrobial DDDs.

Objective To investigate the serum micro-ribonucleic acid-15a(miR-15a)and macrophage mi-gration inhibitory factor(MIF)levels and their relationship with adverse maternal and infant outcomes in pa-tients with gestational diabetes mellitus(GDM).Methods From January 2020 to December 2022,106 patients with GDM who underwent prenatal examination and gave birth in the Hengshui Fourth People's Hospital were selected as the experimental group.Another 106 healthy women who underwent pregnancy examination and delivered in a hospital during the same period were selected as the control group.Detection of serum miR-15a level by real-time fluorescent quantitative polymerase chain reaction and serum MIF levels were detected by enzyme-linked immunosorbent assay.Serum MIF and miR-15a levels were compared between the two groups,and the relationship between miR-15a and MIF levels and adverse maternal and infant outcomes in GDM patients was analyzed by multivariate Logistic regression.Results The serum levels of miR-15a and MIF in the experimental group were higher than those in the control group,the difference was statistically sig-nificant(P＜0.05).The age of patients with adverse maternal and infant outcomes in the experimental group was＞35 years old,the pre-pregnancy body mass index was＞24 kg/m2,the proportion of patients with ad-verse pregnancy history,poor blood glucose control and serum MIF and miR-15a levels were higher than those with good maternal and infant outcomes in the experimental group,and the differences were statistically sig-nificant(P＜0.05).Multivariate Logistic regression analysis showed that age＞35 years old,pre-pregnancy body mass index＞24 kg/m2,adverse pregnancy history,poor blood glucose control and serum miR-15a and MIF were all risk factors for adverse maternal and infant outcomes in the experimental group(P＜0.05).Conclusion Serum miR-15a and MIF levels are abnormally elevated in GDM patients,and serum miR-15a and MIF levels are closely related to adverse maternal and infant outcomes.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.