ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Yinqiao San （YQS） is a classic prescription in Systematic Differentiation of Warm Diseases， which has the effects of pungent dispersing， bitter descending， clearing heat， and removing toxin. It is a classic prescription for the treatment of the onset of warm disease. The prescription contains ten kinds of traditional Chinese medicines， which are in proper compatibility. The ancient and modern physicians often modify the prescription for the treatment of various diseases in children， which has a significant effect. At present， with the rapid development of modern technology， the research on the mechanism of YQS at the molecular level is constantly deepening and improving， which provides new ideas and scientific basis for the treatment of pediatric diseases by YQS. Therefore， this paper summarized and collated the relevant research literature on YQS published by scholars from China and other countries in recent years from six aspects： the textual research on the source of YQS prescription， the theory of formulation， clinical application， active ingredients of traditional Chinese medicine， pharmacological effects， and decocting and administration methods. It expounded on the diseases treated by YQS which were recorded in modern literature， involving the respiratory system， nervous system， rheumatic， immune， and renal disease systems， skin system， infectious system， and its application in diseases such as mucocutaneous lymph node syndrome， viral myocarditis， mesenteric lymphadenitis， and post-nasal drip syndrome. At the same time， it elucidated the mechanism of YQS in the treatment of diseases and its correlation with antiviral， antibacterial， antipyretic， and analgesic effects， improvement of microbiota， regulation of immune function， anti-inflammatory effect， and improvement of pulmonary damage. The decoction time of YQS had a significant effect on its clinical effect， and the best decoction time for its efficacy was 3 to 6 minutes after boiling.

Objective:To explore the relationship between serum osteopontin (OPN), annexin A2 (ANXA2) and recurrence after partial laryngectomy in patients with early-stage glottic laryngeal cancer (EGC).Methods:A retrospective study was conducted by collecting clinical data from EGC patients who underwent partial laryngectomy at Beijing Shijitan Hospital from June 2020 to May 2022. Serum levels of OPN and ANXA2 were measured at the time of admission. Clinical data during the perioperative period were also collected. The recurrence within 2 years after surgery was used as the endpoint event. Patients were divided into a recurrence group and a non-recurrence group based on the occurrence of recurrence. The data were compared between the groups, and Cox regression was used to analyze the correlation between recurrence after partial laryngectomy and key factors. Receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive value of serum OPN and ANXA2 for recurrence within 2 years after surgery.Results:Among 167 EGC patients, 42 patients experienced recurrence within 2 years after surgery (recurrence group), with a median recurrence time of 16.00 (13.75, 19.25) months, and a recurrence rate of 25.15%; 125 patients did experience recurrence within 2 years after surgery (non-recurrence group). Compared to the non-recurrence group, the proportions of poorly differentiated tumors and anterior commissure invasion in the recurrence group were higher, the serum levels of OPN, ANXA2 and testosterone were higher: 52.38% (22/42) vs. 20.80% (26/125), 52.38% (22/42) vs. 20.00% (25/125), (24.26 ± 4.64) μg/L vs. (18.83 ± 4.17) μg/L, (37.62 ± 6.15) μg/L vs. (31.24 ± 5.56) μg/L, (27.26 ± 5.31) nmol/L vs. (22.85 ± 4.62) nmol/L, with significant differences ( P<0.05). Cox regression analysis result showed that recurrence after partial laryngectomy in EGC patients was potentially related to tumor differentiation, anterior commissure invasion, and abnormal serum expression of OPN, ANXA2 and testosterone ( P<0.05). ROC curve analysis revealed that serum OPN and ANXA2 had an area under the curve of 0.80 and 0.79, respectively, showing predictive value, with optimal cutoff values of 21.40 and 34.72 μg/L. Decision curve analysis indicated that serum OPN and ANXA2 had predictive significance for recurrence after partial laryngectomy in EGC patients, and the combined use of pathological grade, anterior commissure invasion, and testosterone improved the net benefit. Conclusions:Recurrence after partial laryngectomy in EGC patients may be associated with elevated serum OPN and ANXA2 levels, which could increase the risk of postoperative recurrence. Early detection of serum OPN and ANXA2 could be valuable for predicting recurrence after surgery in EGC patients.

Objective:To investigate the effect of the embryo cryopreservation duration on pregnancy and obstetric outcome.Methods:A retrospective cohort study of 2 662 frozen-thawed embyro tranfer (FET) cycles was conducted in the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital from January 2016 to December 2020. According to embryo cryopreservation duration, the patients were divided into group A (≤1 year, n=2 115), group B (>1 years and ≤3 years, n=319), group C (>3 years and ≤6 years, n=174), and group D (>6 years, n=54). We used the propensity score matching (PSM) to match the baseline data of oocyte retrieval age of the other three groups according to group D at a ratio of 1∶3. Clinical and obstetric outcomes were compared among the four groups. Multiple logistic regression analysis was used to analyze the effect of oocyte retrieval age, embryo transfer age, the duration of embryo cryopreservation, endometrial preparation scheme, endometrial thickness, the number of transferred embryos and the number of high-quality embryos on pregnancy and live birth outcome. Results:1) Before PSM, there were significant differences in the maternal age at oocyte retrieval and embryo transfer and duration of embryo cryopreservation among the four groups(all P<0.001). 2) After PSM, the baseline characteristics of oocyte retrieval age reached a balance among the four groups. There were no statistical differences in the number of embryos transfer, the number of high-quality embryos, the transferred embryo stage, the endometrial regimen among the groups (all P>0.05). The clinical pregnancy rate [37.04% (20/54)] and the live birth rate [33.33% (18/54)] in group D were lower than those in group A [51.57% (82/159), 40.88% (65/159)], group B [50.00% (65/130), 40.77% (53/130)] and group C [49.59% (61/123), 39.02% (48/123)], but the difference was not statistically significant between the four groups ( P=0.310, P=0.781). There were no statistical differences among the four groups in the ratio of male to female newborns, gestational age, birth weight, preterm delivery rate, low birth weight rate, macrosomia rate, birth defects, and premature repture of membranes (all P>0.05). 3) Multiple logistic regression analysis showed that the number of high-quality embryos transferred affected the clinical pregnancy outcome (before PSM, OR=2.614, 95% CI: 2.168-3.151, P<0.001; after PSM, OR=1.984, 95% CI: 1.406-2.800, P<0.001) and live birth (before PSM, OR=2.708, 95% CI: 2.198-3.336, P<0.001; after PSM, OR=2.122, 95% CI: 1.474-3.053, P<0.001). The duration of embryo cryopreservation does not affect the clinical outcome and live birth (all P>0.05). Conclusion:The duration of embryo cryopreservation does not affect the clinical outcome and live birth, but large sample data are still needed to support this conclusion in the future.

A retrospective analysis was conducted on a case of recurrence during pregnancy of early-stage endometrial cancer (EEC) after fertility-preserving treatment, and literature review was conducted. The patient underwent two cycles of controlled ovarian stimulation and three cycles of frozen-thawed embryo transfer after fertility-preserving treatment, early abortion after the third transfer and meanwhile the recurrence of endometrial cancer was found. Fertility-preserving retreatment was given after multidisciplinary discussion based on the patient's fertility intention, ultrasound, pelvic magnetic resonance imaging and other examinations. After complete remission, the remaining cryopreserved embryos of the patient were tested for euploidy by preimplantation genetic testing, and the euploid embryo was transferred and delivered at term successfully. Fertility-preserving treatment for patients with EEC need comprehensive management to reduce the recurrence rate. Recurrent patients can choose fertility-preserving retreatment under a comprehensive evaluation.

Objective:To explore the relationship between serum osteopontin (OPN), annexin A2 (ANXA2) and recurrence after partial laryngectomy in patients with early-stage glottic laryngeal cancer (EGC).Methods:A retrospective study was conducted by collecting clinical data from EGC patients who underwent partial laryngectomy at Beijing Shijitan Hospital from June 2020 to May 2022. Serum levels of OPN and ANXA2 were measured at the time of admission. Clinical data during the perioperative period were also collected. The recurrence within 2 years after surgery was used as the endpoint event. Patients were divided into a recurrence group and a non-recurrence group based on the occurrence of recurrence. The data were compared between the groups, and Cox regression was used to analyze the correlation between recurrence after partial laryngectomy and key factors. Receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive value of serum OPN and ANXA2 for recurrence within 2 years after surgery.Results:Among 167 EGC patients, 42 patients experienced recurrence within 2 years after surgery (recurrence group), with a median recurrence time of 16.00 (13.75, 19.25) months, and a recurrence rate of 25.15%; 125 patients did experience recurrence within 2 years after surgery (non-recurrence group). Compared to the non-recurrence group, the proportions of poorly differentiated tumors and anterior commissure invasion in the recurrence group were higher, the serum levels of OPN, ANXA2 and testosterone were higher: 52.38% (22/42) vs. 20.80% (26/125), 52.38% (22/42) vs. 20.00% (25/125), (24.26 ± 4.64) μg/L vs. (18.83 ± 4.17) μg/L, (37.62 ± 6.15) μg/L vs. (31.24 ± 5.56) μg/L, (27.26 ± 5.31) nmol/L vs. (22.85 ± 4.62) nmol/L, with significant differences ( P<0.05). Cox regression analysis result showed that recurrence after partial laryngectomy in EGC patients was potentially related to tumor differentiation, anterior commissure invasion, and abnormal serum expression of OPN, ANXA2 and testosterone ( P<0.05). ROC curve analysis revealed that serum OPN and ANXA2 had an area under the curve of 0.80 and 0.79, respectively, showing predictive value, with optimal cutoff values of 21.40 and 34.72 μg/L. Decision curve analysis indicated that serum OPN and ANXA2 had predictive significance for recurrence after partial laryngectomy in EGC patients, and the combined use of pathological grade, anterior commissure invasion, and testosterone improved the net benefit. Conclusions:Recurrence after partial laryngectomy in EGC patients may be associated with elevated serum OPN and ANXA2 levels, which could increase the risk of postoperative recurrence. Early detection of serum OPN and ANXA2 could be valuable for predicting recurrence after surgery in EGC patients.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.