Objective To investigate the clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(rhGM-CSF)combined with bifidobacterium in the treatment of oral mucositis after chemotherapy.Methods A total of 60 post-chemotherapy patients with oral mucositis admitted to Ganzhou Cancer Hospital of Jiangxi Province from January 2023 to December 2024 were selected as subjects,the patients were divided into observation group(n=30)and control group(n=30)by using a randomized digital table method.The control group received rhGM-CSF mouthwash treatment,while the observation group was additionally administered bifidobacterium-lactobacillus triple live capsules orally.Clinical efficacy,symptom scores,inflammatory factor levels,oral microbiota indicators,and treatment safety were evaluated after 2 weeks of treatment.Results After treatment,the total effective rate in observation group was significantly higher than that in control group(P＜0.05).Post-treatment evaluations showed that patients in observation group exhibited lower scores for edema,congestion,and ulceration,along with reduced pain visual analog scores and decreased levels of inflammatory markers including Toll-like receptor 4,lectin-3,and interleukin-8,the difference were statistically significant(P＜0.05).After treatment,the oral microecological flora of patients in observation group,including lactic acid bacteria and bifidobacterium,were higher than that of control group,while porphyromonas gingivalis and fusetella were lower than that of control group,the difference were statistically significant(P＜0.05).Conclusion The clinical effect of rhGM-CSF combined with bifidobacterium in the treatment of oral mucositis after chemotherapy was significant,which could reduce various symptoms of patients,inhibit inflammatory factors,improve oral microecology,and have good safety.

Objectives:To investigate the enhancement of tumor penetration and photodynamic therapy (PDT) efficacy in triple-negative breast cancer by hyaluronidase (HAase) using a novel pH-responsive IR780-loaded photosensitive micelle.Methods:The pH-responsive IR780-loaded photosensitive micelles were prepared using the nanoprecipitation method, and their morphology, size, and encapsulation efficiency were characterized. The in vitro stability and pH-responsive drug release of the micelles were also evaluated. The cytotoxicity of the micelles on triple-negative breast cancer cells (MDA-MB-231) was assessed using a cell counting kit. A nude mouse breast cancer model was established, and HAase was injected intratumorally 24 hours before intravenous injection of the photosensitive micelles. The effect of HAase on the biodistribution and tumor uptake of the micelles was detected using small animal in vivo imaging. CD31 and HIF-1α immunofluorescence staining were performed to investigate the mechanism of HAase-enhanced tumor penetration. The body weight and tumor volume of the mice were measured, and necrosis and apoptosis of tumor tissues were assessed using HE staining and TUNEL staining, respectively. Results:Transmission electron microscopy showed that the micelles had a uniform particle size of approximately 60-70 nm, with a hydrated particle size of (98.03±0.22) nm. The IR780 encapsulation efficiency was 74.15%, with a drug loading content of 2.07%. After 7 days at 4 ℃, there was no significant change in hydrated particle size ( P=0.062). The 24-hour release rates of the micelles in PBS at pH 7.4 and 6.5 were (2.41±0.21)% and (43.69±2.09)%, respectively, showing a significant difference ( P＜0.000 1). The cytotoxicity assay revealed that the cell viability in the micelles group without light exposure was significantly higer than that in the micelles group under light exposure [(97.00±5.38)% vs. (53.27±9.00)%, P=0.000 2]. The micelles were able to target and accumulate in the tumor tissue, and this accumulation increased significantly with HAase treatment. CD31 and HIF-1α immunofluorescence staining indicated that the CD31 signal was enhanced [(0.27±0.05)% vs. (4.57±0.27)%, P＜0.000 1] and the HIF-1α signal was reduced [(5.14±0.38)% vs. (0.08±0.04)%, P＜0.000 1] in the HAase-treated group compared to that in the micelle-only group. After 11 days of treatment with HAase combined with photosensitive micelles, there was no statistically significant difference in mouse body weight ( P＞0.05). However, the tumor volume inhibition rate in the HAase-micelle-mediated PDT group was significantly higher than that in the micelle-mediated PDT group [(87.66±6.37)% vs. (25.34±12.63)%, P=0.002]. Histological staining showed a significant increase in tumor cell necrosis and apoptosis in the HAase-micelle-mediated PDT group. Conclusion:HAase enhances the deep tumor penetration and targeted accumulation of pH-responsive IR780-loaded photosensitive micelles, significantly improves the efficacy of photodynamic therapy in triple-negative breast cancer.

Objectives:To investigate the enhancement of tumor penetration and photodynamic therapy (PDT) efficacy in triple-negative breast cancer by hyaluronidase (HAase) using a novel pH-responsive IR780-loaded photosensitive micelle.Methods:The pH-responsive IR780-loaded photosensitive micelles were prepared using the nanoprecipitation method, and their morphology, size, and encapsulation efficiency were characterized. The in vitro stability and pH-responsive drug release of the micelles were also evaluated. The cytotoxicity of the micelles on triple-negative breast cancer cells (MDA-MB-231) was assessed using a cell counting kit. A nude mouse breast cancer model was established, and HAase was injected intratumorally 24 hours before intravenous injection of the photosensitive micelles. The effect of HAase on the biodistribution and tumor uptake of the micelles was detected using small animal in vivo imaging. CD31 and HIF-1α immunofluorescence staining were performed to investigate the mechanism of HAase-enhanced tumor penetration. The body weight and tumor volume of the mice were measured, and necrosis and apoptosis of tumor tissues were assessed using HE staining and TUNEL staining, respectively. Results:Transmission electron microscopy showed that the micelles had a uniform particle size of approximately 60-70 nm, with a hydrated particle size of (98.03±0.22) nm. The IR780 encapsulation efficiency was 74.15%, with a drug loading content of 2.07%. After 7 days at 4 ℃, there was no significant change in hydrated particle size ( P=0.062). The 24-hour release rates of the micelles in PBS at pH 7.4 and 6.5 were (2.41±0.21)% and (43.69±2.09)%, respectively, showing a significant difference ( P＜0.000 1). The cytotoxicity assay revealed that the cell viability in the micelles group without light exposure was significantly higer than that in the micelles group under light exposure [(97.00±5.38)% vs. (53.27±9.00)%, P=0.000 2]. The micelles were able to target and accumulate in the tumor tissue, and this accumulation increased significantly with HAase treatment. CD31 and HIF-1α immunofluorescence staining indicated that the CD31 signal was enhanced [(0.27±0.05)% vs. (4.57±0.27)%, P＜0.000 1] and the HIF-1α signal was reduced [(5.14±0.38)% vs. (0.08±0.04)%, P＜0.000 1] in the HAase-treated group compared to that in the micelle-only group. After 11 days of treatment with HAase combined with photosensitive micelles, there was no statistically significant difference in mouse body weight ( P＞0.05). However, the tumor volume inhibition rate in the HAase-micelle-mediated PDT group was significantly higher than that in the micelle-mediated PDT group [(87.66±6.37)% vs. (25.34±12.63)%, P=0.002]. Histological staining showed a significant increase in tumor cell necrosis and apoptosis in the HAase-micelle-mediated PDT group. Conclusion:HAase enhances the deep tumor penetration and targeted accumulation of pH-responsive IR780-loaded photosensitive micelles, significantly improves the efficacy of photodynamic therapy in triple-negative breast cancer.

Objective To investigate the clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(rhGM-CSF)combined with bifidobacterium in the treatment of oral mucositis after chemotherapy.Methods A total of 60 post-chemotherapy patients with oral mucositis admitted to Ganzhou Cancer Hospital of Jiangxi Province from January 2023 to December 2024 were selected as subjects,the patients were divided into observation group(n=30)and control group(n=30)by using a randomized digital table method.The control group received rhGM-CSF mouthwash treatment,while the observation group was additionally administered bifidobacterium-lactobacillus triple live capsules orally.Clinical efficacy,symptom scores,inflammatory factor levels,oral microbiota indicators,and treatment safety were evaluated after 2 weeks of treatment.Results After treatment,the total effective rate in observation group was significantly higher than that in control group(P＜0.05).Post-treatment evaluations showed that patients in observation group exhibited lower scores for edema,congestion,and ulceration,along with reduced pain visual analog scores and decreased levels of inflammatory markers including Toll-like receptor 4,lectin-3,and interleukin-8,the difference were statistically significant(P＜0.05).After treatment,the oral microecological flora of patients in observation group,including lactic acid bacteria and bifidobacterium,were higher than that of control group,while porphyromonas gingivalis and fusetella were lower than that of control group,the difference were statistically significant(P＜0.05).Conclusion The clinical effect of rhGM-CSF combined with bifidobacterium in the treatment of oral mucositis after chemotherapy was significant,which could reduce various symptoms of patients,inhibit inflammatory factors,improve oral microecology,and have good safety.

OBJECTIVE: To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS). METHODS: A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c.471delC (p.F158Lfs*42) and c.1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+PM2_Supporting+PP4) and likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4). CONCLUSION Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.
Pregnancy ; Child ; Female ; Humans ; Walker-Warburg Syndrome ; Prenatal Diagnosis ; Fetus ; Genetic Counseling ; Genomics ; Mutation

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective This study examined the research status and development process of FU Qingzhu’s Obstetrics and Gynecology (Fu Qing Zhu Nv Ke,《傅青主女科》, FQZNK) in the past 40 years with bibliometrics and visual analysis. Methods Retrieved all related literature in the research field of FQZNK from the domestic and foreign databases: China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and Web of Science (WOS) core database, including Science Citation Index Expanded (SCIE), Social Sciences Citation Index (SSCI), and Arts & Humanities Citation Index (A&HCI). The search range was from January 1, 1980 to March 10, 2021. In addition, bibliometrics and CiteSpace 5.7.R2 software were used to analyze literature types, published journals, cited literature, the number of author publications, co-author networks, co-institution networks, keyword co-occurrence networks, keyword clusters, and keyword bursts. Results A total of 678 valid records were included in the final dataset. Literature types, high publication journals, highly cited literature, high-yield institutions, high-yield research teams, and high-productivity scholars in this research field were found through bibliometrics. Literature types can be divided into four categories, among which 451 are theoretical studies on academic thoughts of FQZNK, accounting for 66.5% of the included journals. The Journal of Shanxi Traditional Chinese Medicine had the largest volume of published articles (61), accounting for 9.0% of the total number of the included journals. The most cited literature was ZHOU Mingxin’s article “Using the quantitative method to discuss author’s authenticity and formula characteristics of FU Qingzhu’s Obstetrics and Gynecology”, which was cited 94 times. Hunan University of Chinese Medicine, the institution with the most publications, published 45 articles, and YOU Zhaoling, the most published author, published 33 articles. Moreover, it was found that most high-yield researchers came from high-yield institutions and that Hunan University of Chinese Medicine had the most research on FQZNK. Keyword co-occurrence analysis revealed that the keyword “FQZNK” had the highest frequency (597 times) and the highest centrality (1.00). Keyword cluster analysis used the Log-Likelihood Ratio (LLR) algorithm to form eleven important clusters: #0 treatment aiming at its root causes, #1 gynecopathy, #2 Siwu Decoction (四物汤), #3 FU Qingzhu, #4 post-partum, #5 infertility, #6 dysmenorrhea, #7 sterility, #8 coordinate the heart and kidney, #9 Danggui Buxue Decoction (当归补血汤), and #10 treatment. It was found that the prescriptions of FQZNK were studied mainly before 2000, the theoretical studies were mainly conducted before 2010, and its clinical application was mainly explored from 2010 until now. Diseases such as dysmenorrhea, morbid vaginal discharge, infertility, metrorrhagia, and polycystic ovarian syndrome (PCOS) have recently become popular topics in this field. Conclusion The current study provides more scientific, accurate, and comprehensive scientific support for further research and development of traditional Chinese medicine (TCM) in FQZNK. With this foundation, people can use burst detection to ascertain the current hotspots in research, get their development trends, and forecast future research directions. In addition, infertility, morbid vaginal discharge, flooding, and PCOS treatments based on TCM syndrome differentiation are currently popular research topics for FQZNK.

Objective:To investigate the effect of Budesonide (BUD) on pulmonary vascular development and the expression of vascular endothelial growth factor (VEGF) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in newborn rats with bronchopulmonary dysplasia (BPD) caused by intrauterine infection.Methods:The 15-day-pregnant SD rats were divided into control group and infection group [intraperitoneal injection of 0.35 mg/(kg·d) lipopolysaccharide], and the newborn rats born by the above groups were divided into 3 groups: BUD group (0.5 mg of BUD suspension), normal control group (NC group, equal amount of 9 g/L saline), BPD group (equal amount of 9 g/L saline), with 40 rats in each group, all of them were inhaled twice a day for 14 days.Ten newborn rats were selected at birth, on the 3 rd, 7 th and 14 th day after administration.Pulmonary histopathological changes and radial alveolar counts (RAC) were observed after HE staining, and the thickness of alveolar respiratory membrane was measured; the platelet-endothelial cell adhesion molecule (PECAM-1/CD 31) in lung tissue was detected by immunohistochemistry, and the density of pulmonary microvessels was calculated; the expressions of VEGF, NLRP3 and Caspase-1 were detected by Western blot; and the levels of serum interleukin( IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay. Results:With the increase of day-old, the lung tissue of newborn rats in NC group was gradually developed and matured, the structure of alveoli was clear, the size was uniform, the count was significantly increased, and no obvious pathological changes were observed.In BPD group, the lung tissue structure was disordered, the alveoli were different in size and few in count, and inflammatory cells were exuded from the alveoli or the alveoli space.Compared with BPD group, the pathological changes of lung tissue in BUD group were significantly reduced.On the 3 rd, 7 th and 14 th day after administration, compared with NC group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were lower, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly higher, and the differences were statistically significant(all P<0.05). Compared with BPD group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were significantly higher, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly lower, and the differences were statistically significant (all P<0.05). Conclusions:The occurrence and development of pathological changes of BPD newborn rats caused by intrauterine infection can affect the development of pulmonary vessels through the inflammatory response of lung tissue.BUD can alleviate pathological changes in lung tissues of BPD newborn rats by reducing inflammatory reaction and up-regulating VEGF expression, promoting pulmonary vascular remodeling, and increasing pulmonary microvascular density.

Objective:To investigate the pathogenic gene locus and prenatal genetic diagnosis of 54 families with oculocutaneous albinism (OCA).Methods:This retrospective study enrolled 54 OCA probands and their families from Gansu Province Maternal and Child Health Care Hospital from May 2014 to May 2020. TYR gene variation screening was performed on the probands by Sanger sequencing. Those with negative results were analyzed by high-throughput sequencing, and further verification was performed on their parents by Sanger sequencing. Among the 54 families, 15 ml amniotic fluid were collected from 16 women at 18-21 gestational weeks in their subsequent pregnancy. Sanger sequencing combined with short tandem repeats sequence for linkage analysis were performed for genetic analysis. All data were analyzed using descriptive statistical analysis. Results:Out of the 54 OCA probands, 48 were diagnosed as OCA1, five were OCA2 and one was OCA4 based on the Sanger sequencing and high-throughput sequencing detection. A total of 26 different variation sites were involved in the 48 OCA1 probands, including 15 missense mutations, five nonsense mutations, three splicing mutations, and three frame-shift mutations, among which, c.929insC (29%, 28/96) was the most frequent mutation, followed by c.896G>A (11%, 11/96), c.832C>T (8%, 8/96) and c.703T>C (5%, 5/96). The diagnosis was confirmed in all 16 fetuses in the 16 families that underwent prenatal diagnosis. Five of them were affected and their mothers chose to terminate the pregnancies, the other 11 pregnancies continued to delivery, including seven heterozygous carriers and four fetuses without the same pathogenic allele as the proband. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. All 11 children were in good health during telephone follow-up one month after birth. Postnatal validations were consistent with the prenatal tests.Conclusions:Genetic diagnosis could accurately identify various types of OCA and help to provide prenatal diagnosis and fertility consultation for subsequent pregnancies.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.