Background: Inhalation-based combination therapy has gained increasing attention for local treatments. However, a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients, particularly in traditional Chinese medicine (TCM) formulations. Objective: This study investigates a novel PulmoSphere-based inhalable carrier designed for the sustained pulmonary release of multiple active ingredients, using Shuang-Huang-Lian as a model TCM formulation containing three chemical markers. Materials and methods: The carrier was developed using PulmoSphere technology, incorporating phospholipid complexes of the chemical markers and hyaluronic acid (HA) into spray-dried microparticles. The aerodynamic properties, release characteristics, pulmonary distribution, and anti-inflammatory efficacy of different formulations were evaluated in vitro and in mice. Results: The microparticles retained the excellent aerodynamic properties of conventional PulmoSphere particles, with a mass median aerodynamic diameter of approximately 3.1 μm and a fine particle fraction of approximately 55%. Compared to free Shuang-Huang-Lian or phospholipid complex-loaded PulmoSphere particles, the HA-containing particles prolonged the retention of chemical markers in the lung epithelial lining fluid, demonstrating sustained release in vivo. Additionally, the HA-containing formulation enhanced the exposure of the three chemical markers to immune cells and lung tissues, leading to improved and prolonged anti-inflammatory effects, even at decreased doses. Conclusion: This novel inhalable particle system represents a promising approach for sustained pulmonary co-delivery of multiple active ingredients, offering enhanced and extended local therapeutic efficacy.

Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

Objective To analyze the risk factors for meconium-stained amniotic fluid(MSAF)in preterm infants and the clinical outcome and prognosis of preterm infants.Methods Preterm infants with gestational age＜37 weeks delivered in Zhangjiajie People's Hospital from January 2022 to December 2023 were used as the study subjects,31 cases with MSAF were in MSAF group,and 31 cases of preterm infants hospitalized during the same period without MSAF were randomly paired in the ratio of 1∶1 to select with gestational age-body mass matching as non-MSAF group.Retrospective collection and analysis of pregnancy and perinatal conditions of mothers of preterm infants in two groups,comparing the differences of related factors between two groups of children;Logistic regression analysis of risk factors related to MSAF in preterm infants;comparing the complications and clinical outcomes of preterm infants in two groups.Results A total of 387 preterm infants with gestational age＜37 weeks were collected during the study period,including 31 preterm infants with comorbid MSAF,and the prevalence of MSAF in preterm infants was 8.0％.MSAF group had a higher incidence of advanced maternal age,premature rupture of membranes＞18 hours,antepartum fever,and cholestasis during pregnancy than non-MSAF group.Logistic regression analysis suggested that combined cholestasis during pregnancy and white blood cell count ≥ 30× 109/L within 6 hours after birth increased the incidence of MSAF in preterm infants.There was no statistically significant difference in the results of postnatal umbilical artery blood gas analysis between two groups of preterm infants.The proportion of leukocyte count ≥30×109/L,ultrasensitive C-reactive protein＞0.8 mg/L,and interleukin 6＞6 pg/L in MSAF group was higher than that of non-MSAF group in the 6 hours after birth.MSAF group had a higher incidence of intrauterine infectious pneumonia,feeding intolerance,and necrotizing small bowel colitis in neonates than non-MSAF group.Conclusion Advanced maternal age,intrauterine infections,and combined intrahepatic cholestasis during pregnancy may be the major risk factors for MSAF in preterm infants.MSAF preterm infants have a higher prevalence of intrauterine infectious pneumonitis,feeding intolerance,and necrotizing small bowel colitis in newborns,as well as longer hospital stays.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective To analyze the risk factors for meconium-stained amniotic fluid(MSAF)in preterm infants and the clinical outcome and prognosis of preterm infants.Methods Preterm infants with gestational age＜37 weeks delivered in Zhangjiajie People's Hospital from January 2022 to December 2023 were used as the study subjects,31 cases with MSAF were in MSAF group,and 31 cases of preterm infants hospitalized during the same period without MSAF were randomly paired in the ratio of 1∶1 to select with gestational age-body mass matching as non-MSAF group.Retrospective collection and analysis of pregnancy and perinatal conditions of mothers of preterm infants in two groups,comparing the differences of related factors between two groups of children;Logistic regression analysis of risk factors related to MSAF in preterm infants;comparing the complications and clinical outcomes of preterm infants in two groups.Results A total of 387 preterm infants with gestational age＜37 weeks were collected during the study period,including 31 preterm infants with comorbid MSAF,and the prevalence of MSAF in preterm infants was 8.0％.MSAF group had a higher incidence of advanced maternal age,premature rupture of membranes＞18 hours,antepartum fever,and cholestasis during pregnancy than non-MSAF group.Logistic regression analysis suggested that combined cholestasis during pregnancy and white blood cell count ≥ 30× 109/L within 6 hours after birth increased the incidence of MSAF in preterm infants.There was no statistically significant difference in the results of postnatal umbilical artery blood gas analysis between two groups of preterm infants.The proportion of leukocyte count ≥30×109/L,ultrasensitive C-reactive protein＞0.8 mg/L,and interleukin 6＞6 pg/L in MSAF group was higher than that of non-MSAF group in the 6 hours after birth.MSAF group had a higher incidence of intrauterine infectious pneumonia,feeding intolerance,and necrotizing small bowel colitis in neonates than non-MSAF group.Conclusion Advanced maternal age,intrauterine infections,and combined intrahepatic cholestasis during pregnancy may be the major risk factors for MSAF in preterm infants.MSAF preterm infants have a higher prevalence of intrauterine infectious pneumonitis,feeding intolerance,and necrotizing small bowel colitis in newborns,as well as longer hospital stays.

Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

OBJECTIVE To investigate the effect of individualized repositioning maneuver in the treatment of posterior semicircular canal benign paroxysmal positional vertigo(PC-BPPV)with limited neck movement.METHODS There were 163 patients with PC-BPPV admitted to the Department of Otolaryngology of Xiaolan People's Hospital of Zhongshan from January,2019 to July,2022 who were selected and divided into observation group(57 cases)and control group(106 cases)according to whether there was neck movement limitation or not.The control group was divided into control group 1(51 cases)and control group 2(55 cases)based on different reduction methods.The control group 1 were treated with modified Epley maneuver,and the observation group and the control group 2 were treated with individualized Epley maneuver.The cure rate and effective rate were compared among the three groups.The scores of vestibular symptom index(VSI),Berg balance scale(BBS)and the dimension scores of vertigo handicap inventory(DHI)were compared among the three groups before and after treatment.RESULTS There was no significant difference in the cure rate(84.37%vs.81.82%vs.80.70%)and effective rate(11.76%vs.10.91%vs.12.28%)among the three groups(P>0.05).After treatment,the scores of each dimension of VSI and DHI of PC-BPPV patients of the three groups decreased(P<0.01),and the scores of BBS increased(P<0.01),and there was no statistically significant difference in the scores of VSI(23.19±3.88 vs.23.70±4.01 vs.23.46±3.92),BBS(45.56±5.02 vs.45.14±4.98 vs.44.84±5.11)and each dimension of DHI among the three groups(P>0.05),respectively.CONCLUSION The individual Epley maneuver can effectively improve the vertigo status of patients with PC-BPPV with limited neck movement.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.