OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

AIM:To assess the influence of preoperative lacrimal passage probing and dilation on the therapeutic effectiveness of nasolacrimal silicone intubation in cases of incomplete primary acquired nasolacrimal duct obstruction(PANDO).METHODS: A retrospective case-control clinical study was conducted. The study included patients with incomplete PANDO who underwent nasolacrimal silicone intubation at the hospital between October 2022 and October 2024. Participants were categorized into two groups based on their receipt of nasolacrimal duct probing and dilation prior to intubation. Group A consisted of patients who had undergone one or more sessions of nasolacrimal duct probing and dilation before nasolacrimal silicone intubation, while Group B included patients who did not receive nasolacrimal duct probing and dilation before intubation. All patients had their nasolacrimal silicone tubes removed 3 mo postoperatively and were monitored for 6 mo following tube removal to evaluate surgical success rates.RESULTS: A total of 136 patients(152 eyes)completed the six-month follow-up period. The overall surgical success rate for both groups was 72.4%(110/152 eyes).Group A included 22 males and 36 females, mean age 58.09±11.07 y, and achieved a success rate of 82.8%(53/64 eyes), while Group B included 27 males and 51 females, mean age 59.35±8.84 y and attained a success rate of 64.8%(57/88 eyes). The difference in surgical success rates between the two groups was statistically significant(P=0.014). Furthermore, Group A achieved a complete success rate of 67.2%(43/64 eyes), compared to 47.7%(42/88 eyes)in Group B, with this difference also reaching statistical significance(P=0.017). No serious postoperative complications were observed in either group.CONCLUSION: Nasolacrimal silicone intubation is a safe and effective intervention for incomplete PANDO, with preoperative nasolacrimal duct probing and dilation potentially enhancing therapeutic outcomes.

ObjectiveTo investigate the current awareness and optimization recommendations on pneumonia with unknown etiology (PUE) surveillance among Shanghai healthcare professionals, and to provide evidence for the improvement of the surveillance system. MethodsIn December 2024, healthcare professional participants from diverse medical and health institutions were randomly selected within each stratum using a stratified cluster sampling method in all 16 districts of Shanghai for questionnaire surveys on their knowledge and suggestions for optimization of the PUE surveillance system. Descriptive statistics analyses, multivariate logistic regressions, and content analyses were used for data analyses. ResultsA total of 385 survey subjects were involved in the study, including 119 professional staffs from disease prevention and control centers and 266 from medical institutions. Those who understood the case definition for PUE correctly accounted for 67.01% (258/385). Multivariate regression model analyses showed that female gender (aOR=2.22, 95%CI: 1.36‒3.66), professionals from disease control institutions (aOR=2.02, 95%CI: 1.12‒3.72), and those who self-assessed as being familiar with the monitoring system (aOR=2.18, 95%CI:1.23‒3.89) had better understanding of the definition. Overall, 89.61% (345/385) of the survey subjects acknowledged the necessity of the surveillance system. Small number of cases meeting the case definition (54.46%, 214/379), insufficient diagnostic awareness (39.84%, 151/379), and lack of incentives for case reporting (29.29%, 111/379) were major problems for the current surveillance system, with variations observed across different types of institutions. Suggested segments for optimizing the surveillance system included monitoring purpose, case definition, form of monitoring and reporting procedure, organization mechanism, and epidemiological investigation and response. ConclusionThe necessity of PUE surveillance is commonly recognized among healthcare workers. However, the existing system falls short in terms of mastery of case definition and overall surveillance adaptability. There is an urgent need for optimization and improvement to enhance the capacity for preventing and controlling emerging and sudden respiratory infectious diseases.

Objective To propose a framework for risk assessment and stepwise management of pulmonary nodules based on existing guidelines and key studies, and to clarify the boundaries for triage, workup escalation, and referral in different detection scenarios. Methods A problem-oriented evidence synthesis approach was used, prioritizing Chinese expert consensus, Fleischner Society Guidelines, British Thoracic Society (BTS) Guidelines, and Lung-RADS. This was supplemented by studies on risk models, imaging measurements, liquid biopsy, tissue sampling, and surgical treatments. This paper is not presented as a formal consensus or a validated clinical pathway. Results A three-tiered framework consisting of basic non-invasive assessment, advanced assessment, and invasive diagnosis was established. It specified the applicable populations, boundaries for the use of risk models, imaging review, management of conflicting results, evaluation of histopathological consistency, and post-intervention follow-up. Liquid biopsy, genetic testing, and artificial intelligence were defined as investigational or adjunctive tools. Conclusion This framework can serve as a preliminary reference for multidisciplinary teams in developing local protocols. It cannot replace applicable guidelines, pathological diagnosis, shared decision-making with patients, or real-world validation.

Objective:To investigate the impact of the number of cesarean deliveries on adverse maternal and neonatal outcomes.Methods:A retrospective analysis was conducted on 11 904 singleton pregnant women who underwent cesarean delivery at the Third Affiliated Hospital of Guangzhou Medical University from January 1st, 2019 to December 31st, 2023. The women were grouped according to the number of cesarean deliveries: those undergoing their first cesarean delivery (1CD group, 7 231 cases), those undergoing their second cesarean delivery (2CD group, 3 749 cases), those undergoing their third cesarean delivery (3CD group, 841 cases), and those undergoing their fourth or more cesarean deliveries (4CD group, 83 cases). Differences in clinical characteristics, related surgical procedures, and adverse maternal and neonatal outcomes among the groups were compared. Binary logistic regression analysis was used to assess the impact of the number of cesarean deliveries on related surgical procedures and adverse maternal and neonatal outcomes.Results:(1) During the 5-year period, the total number of women undergoing cesarean delivery in our hospital showed a slight downward trend, while the proportion of women undergoing three or more cesarean deliveries increased. (2) Compared with women undergoing their first cesarean delivery, women in each repeat cesarean delivery group were older, had higher proportions of advanced maternal age and pre-pregnancy body mass index, and had more pregnancies, deliveries, and induced abortions; the incidence of placenta previa, placental implantation, antepartum hemorrhage, gestational hyperglycemia, and failed trial of labor requiring conversion to surgery was higher, while the incidence of premature rupture of membranes was lower; the proportions of ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and postoperative intestinal obstruction were higher, and the amount of postpartum hemorrhage was greater; the gestational age at delivery of neonates was earlier, but the rates of preterm birth at 28-31 +6 and 32-33 +6 weeks of gestation were lower; the differences were statistically significant ( P<0.05) for all comparisons. (3) The number of cesarean deliveries was not an independent risk factor for the dose-dependent occurrence of placenta previa (a OR=0.99, 95% CI: 0.98-1.01; P=0.261). In women without placenta previa, the number of cesarean deliveries was not a risk factor for placental implantation (a OR=1.12, 95% CI: 0.90-1.39; P=0.320). However, in women with placenta previa, the number of cesarean deliveries was a risk factor for placental implantation (a OR=4.01, 95% CI: 3.08-5.22; P<0.001). In the overall population, the number of cesarean deliveries was a risk factor for ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, bladder rupture repair, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and preterm birth (all P<0.05). However, the number of cesarean deliveries was not a risk factor for postoperative intestinal obstruction, admission to the intensive care unit, neonatal asphyxia, admission to the neonatal intensive care unit, or neonatal death (all P<0.05). Conclusions:The number of cesarean deliveries could lead to adverse maternal and neonatal outcomes, but the relationship is not simply dose-dependent. It is speculated that the occurrence of severe adverse maternal and neonatal outcomes is more closely related to maternal complications and comorbidities, as well as whether multidisciplinary comprehensive management was received.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.

Objective To evaluate the effect of laparoscopic surgery on incarcerated inguinal hernia(IIH)in children.Methods A total of 81 IIH children treated at Jinhua Maternal & Child Health Hospital from September 2018 to December 2023 were selected as subjects.The children were divided into laparoscopic surgery group(n=45)and open surgery group(n=36).Comparative analysis was conducted on admission age,gender,duration of incarceration,surgical timing,intraoperative hernia contents,and postoperative complications between two groups.Results Operative duration,intraoperative blood loss,postoperative bowel function recovery time,number of occult hernias,and hospitalization duration in laparoscopic surgery group were statistically better than those in open surgery group(P＜0.05).There were fewer postoperative complications in laparoscopic group compared to open surgery group,there was significant difference between two groups(P＜0.05).Conclusion Compared with traditional open surgery,laparoscopic surgery for IIH in children has the advantages of less trauma,shorter operation time and hospitalization time,and less intraoperative bleeding.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.