ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

The prevalence of dry eye among children has been progressively increasing each year; however, clinical diagnosis remains challenging due to the unique physiological attributes of the pediatric tear film functional unit, as well as symptoms that are often atypical and clinical signs that differ from those seen in adults. In healthy children, tear secretion is generally greater, the meibomian gland structure is typically more intact, and the meibum composition and physicochemical properties are more favorable for the maintenance of tear film stability. Compared to adults, the etiology of pediatric dry eye is more frequently associated with meibomian gland dysfunction, allergic ocular conditions, orthokeratology lens wear, environmental influences, such as growing screen time, and systemic disorders. Affected children frequently exhibit non-specific symptoms such as excessive blinking or rubbing of the eyes, which may be overlooked due to their limited ability to verbalize discomfort. Clinical signs can include conjunctival hyperemia, decreased tear meniscus height, and corneal epithelial punctate lesions, though these tend to be milder or less distinct compared with adults. Diagnostic requires the use of age-appropriate tear metrics, such as the Schirmer test and tear film breakup time, alongside ocular surface evaluation, with particular attention to features specific to children that distinguish it from dry eye in adults. Going forward, it is essential to establish and validate pediatric-specific diagnostic criteria to improve ocular surface health and maximize visual quality in this vulnerable population.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

Objective: To explore the assocation of the family environment and depressive symptoms among primary and middle school students, so as to provide suggestions for further maximizing the utility of family environment in the growth of primary and secondary school students, as well as prevention and intervention of depressive symptoms among children and adolescents. Methods: From June to July 2024, through a multistage cluster random sampling method, 8 800 primary and middle school students aged 10 to 18 from 36 schools in 3 cities (Datong, Lvliang, Linfen) in Shanxi Province. A self designed questionnaire was used to conduct a family environment survey, including family socioeconomic conditions, family structure, family parenting behavior, family member health behavior, etc; and the depression symptoms of primary and secondary school students were investigated by Patient Health Questionnaire-9. The χ 2 test and binary Logistic regression to method were used to analyze the association of the family environment with depressive symptoms among primary and secondary school students, and to analyze gender and urban-rural heterogeneity in this association. Results: The detection rate of depressive symptoms among primary and middle school students was 46.7% ( n = 4 111 ). Among them, the detection rates of depressive symptoms for male and female students were 45.7% and 47.7% respectively, and the detection rates for rural and urban students were 48.0% and 44.9% respectively. The results of binary Logistic regression model showed that in the family environment, factors such as the father s education level (junior high school: OR =0.84), self assessed family socio economic status (average: OR =0.78, good: OR =0.80), parental support and understanding (yes: OR = 0.55 ), family atmosphere (harmonious: OR =0.66), living arrangement (living only with father or mother: OR =1.31, living with parents and grandparents: OR =1.19), and family rearing style (combining punishment and reward: OR =1.42, punishment only: OR =1.25) were related to depressive symptoms in primary and middle school students in Shanxi Province ( P <0.05). From the perspective of gender heterogeneity, the living arrangement (living only with father or mother: OR =1.67, others: OR =1.67) had a statistically significant association with depressive symptoms in male students ( P <0.05). From the perspective of urban rural heterogeneity, the living arrangement (living only with father or mother: OR =1.38) had a statistically significant association with depressive symptoms in rural primary and middle school students ( P <0.05). Conclusions The family environment has an important impact on depressive symptoms in primary and middle school students. Family functioning should be fully exerted to prevent depressive symptoms in primary and middle school students.

Objective: To analyze the distribution characteristics of fluoride and trichloromethane in drinking water in rural schools in Guizhou Province and assess their health risks, so as to provide a scientific basis for ensuring the safety of drinking water in rural schools. Methods: During the dry season (March to May) and wet season (July to September) of 2020 to 2022, 788 rural primary and secondary schools in agricultural counties (districts) in Guizhou Province were selected for investigation by using a direct sampling method. A total of 1 566 drinking water samples were collected from these schools, and the mass concentrations of fluoride and trichloromethane in the water samples were detected. The Mann-Whitney U test was used for intergroup comparison, and a health risk assessment model was employed to evaluate the health risks of students oral intake of fluoride and trichloromethane. Results: From 2020 to 2022, the mass concentrations of fluoride and trichloromethane in the drinking water of rural schools in Guizhou Province all met the standards, and the ranges were no detection to 0.99 mg/L and (no detection to 0.06)×10 -3 mg/L, respectively. The mass concentrations of fluoride in dry and wet seasons were 0.05(0.05,0.10), 0.05(0.05,0.10) mg/L, the mass concentrations of trichloromethane were [0.02(0.02,1.00)]×10 -3 , [0.02(0.02,1.00)]×10 -3 mg/L, the mass concentrations of fluoride in factory water and terminal water were 0.05(0.05,0.05), 0.05(0.05,0.10) mg/L, and the differences were not statistically significant ( Z=-0.04, -0.88, - 0.98 , P >0.05). There was a statistically significant difference in the mass concentration of trichloromethane between factory water and peripheral water [0.02(0.02,0.02)×10 -3 , 0.02(0.02,1.05)×10 -3 mg/L]( Z=-2.16, P < 0.05 ). The non-carcinogenic risk assessment values for students oral exposure to fluoride and trichloromethane were in the range of 0.01(0.01,0.03)-0.03(0.03,0.06) and [0.26( 0.26 ,14.54)]×10 -4 -[0.52(0.52,48.62)]×10 -4 , respectively, all of which were at acceptable levels; the carcinogenic risk assessment values for oral exposure to trichloromethane were in the range of [0.08(0.08, 4.51 )]×10 -7 -[0.16(0.16,15.07)]×10 -7 , indicating a low risk. Conclusions The health risks of students expore to fluoride and trichloromethane in drinking water in rural schools of Guizhou Province are low. It is necessary to strengthen the standardized management of disinfection in some rural drinking water projects and the monitoring of fluoride in water sources to reduce the exposure risk to children.

ObjectiveTo investigate the protective effect and mechanism of action of flavonoid combination of Alpiniae Officinarum Rhizoma （A. officinarum） against Helicobacter pylori （H. pylori） gastritis in mice. MethodsAfter acclimatization for one week， 56 SPF-grade healthy C57BL/6J mice were gavaged with mixed antibiotics for three consecutive days. They were randomly divided into a normal group， model group， positive drug group （triple therapy group）， and low- and high-dose groups （100， 200 mg·kg^-1） of flavonoid combination of A. officinarum. The H. pylori gastritis mice model was established by gavage with H. pylori bacterial suspension in each group except for the normal group. After successful modeling， mice were administrated with corresponding drugs once a day for two weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric tissue. Rapid urease test paper was used to detect the positive rate of H. pylori. Silver staining was used to observe the H. pylori adherence on the surface of gastric tissue. Immunohistochemistry was used to detect the protein expression of interleukin-8 （IL）-8 and myeloid differentiation factor （MyD88） in gastric tissue. The serum levels of IL-6， tumor necrosis factor-α （TNF-α）， IL-8， and IL-1β were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） protein were detected by Western blot. ResultsCompared with those in the normal group， mice in the model group had lower gastric weight coefficients， higher pH of gastric juice， 100% H. pylori infection rate， and significantly changed gastric histopathology. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the model group were significantly elevated， and the serum levels of inflammatory factors IL-6， TNF-α， IL-8， and IL-1β were significantly up-regulated in mice. Compared with that in the model group， the gastric weight coefficient of mice in each treatment group of the flavonoid combinations of A. officinarum was elevated （P<0.01）， and the pH of gastric juice was reduced （P<0.01）. The infection rate of H. pylori was reduced. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the treatment groups were significantly reduced （P<0.01）， and the serum levels of inflammatory factors IL-6， TNF-α， IL-8， and IL-1β were significantly reduced in a dose-dependent manner （P<0.01）. The flavonoid combinations of A. officinarum down-regulated the expression of PI3K and Akt proteins in H. pylori gastritis-infected cells （P<0.01）. ConclusionThe protective effect of flavonoid combinations of A. officinarum against H. pylori gastritis is associated with the inhibition of H. pylori infection rate and regulation of PI3K/Akt signaling pathway， resulting in inhibiting the release of inflammatory factors.

This article systematically analyzes the historical evolution of the name， medicinal parts， origin， harvesting， processing and other aspects of Houttuyniae Herba（HH） by referring to the medical books， prescription books and other documents of the past dynasties， combined with the research materials related to modern and contemporary times， in order to provide a basis for the development of famous classical formulas containing this herb. In ancient literature， HH was often referred to as "Ji" and "Jicai"， the name of "Ji" was first recorded in Mingyi Bielu during the Han and Wei dynasties， and the name of Yuxingcao was first seen in Lyuchanyan Bencao during the southern Song dynasty and has continued to this day. The origin of HH used throughout history is consistent， all of which are the whole herb or aboveground parts of Houttuynia cordata in Saururaceae family. HH recorded throughout history has a wide range of production areas， mostly self-produced self-marketing. In ancient times， fresh HH was often used as medicine by pounding its juice without involving any processing steps. Both fresh and dried products can be used as medicine， the fresh products uses the whole plant， while the dried products uses the aboveground parts， which are cleaned， selected and processed before use. Fresh products are harvested regardless of season， while dried products are harvested in both summer and autumn， with summer as the best. In ancient times， there were no specific requirements for the quality of HH， while in modern times， "intact stems and leaves with a strong fishy smell" are preferred. In addition， the medicinal properties of HH have undergone significant changes from ancient to modern times. In the early period， it was believed that its medicinal property was slightly warm， until the 1977 edition of Chinese Pharmacopoeia officially changed it to slightly cold. Both ancient and modern literature states that HH can be used for the treatment of carbuncle and malignant sores， Lyuchanyan Bencao for the first time introduced HH fresh juice can relieve summer heat， since Diannan Bencao recorded that it can be used for lung carbuncle， and gradually developed into the first choice for the treatment of lung carbuncle. Based on the research results， it is suggested that fresh herb or dried aboveground parts of H. cordata are used as medicine when developing famous classical formulas.

Erectile dysfunction （ED） is one of the most common manifestations of male reproductive system damage， and it is also a common complication of diabetes mellitus （DM）. ED is closely related to the patient’s quality of life， sexual partner relationship， and family stability. In addition， it is an early warning signal for many physical diseases. As the incidence of DM keeps growing， the incidence of diabetes mellitus-induced erectile dysfunction （DMED） increases accordingly. Currently， drug treatment for ED presents limited effects， and the treatment of DMED is more difficult. Therefore， developing effective and safe drugs is a clinical problem that needs to be solved urgently. Recent studies have proved that traditional Chinese medicine （TCM） can alleviate oxidative stress， reduce inflammation， and modulate autophagy by regulating multiple signaling pathways， thus ameliorating DMED， showing definite therapeutic effects via multiple pathways， targets， and links. Multiple signaling pathways such as phosphatidylinositol-3-kinase/protein kinase B （PI3K/Akt）， nitric oxide （NO）-cyclic guanosine monophosphate （cGMP）， Ras homolog family member A （RhoA）/Rho， nuclear factor erythroid 2-related factor 2 （NRF2）， mitogen-activated protein kinase （MAPK）， adenosine monophosphate-activated protein kinase （AMPK）， and protein kinase C （PKC） mediate the occurrence and development of DMED， while there is still a lack of conclusive records. By reviewing relevant articles published in recent years， this paper summarizes the role of the above-mentioned signaling pathways in the occurrence and development of DMED and the research progress in TCM treatment of DMED via regulation of related signaling pathways. This review is expected to provide new ideas and references for further clinical diagnosis and treatment， basic research， and drug development.