This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

Dry eye disease(DED)is a multifactorial disorder with an unclear pathogenesis. Advances in omics technologies have introduced a novel medical research approach, enabling the identification of global response variables from a single-factor perspective. However, multi-omics methods integrate multiple omics datasets to analyze all potential response variables, generating multidimensional and evidence-supported holistic inferences. These insights help elucidate functional impairments of ocular cells and biomolecular processes during disease progression, thereby revealing correlations between biomolecules and complex diseases. This review summarizes the application of multi-omics technologies in clarifying the pathogenesis and intricate molecular mechanisms of dry eye disease. Distinctive features from genomics, transcriptomics, proteomics, metabolomics, and microbiomics are integrated to deepen the understanding of the pathogenesis and complex molecular mechanisms underlying dry eye disease.

It is considered that "turbid pathogen damaging the clear， and the loss of clarity and harmony regulation" is the core pathogenesis of esophageal precancerous lesions， with turbid pathogen persisting throughout the disease course. Turbid pathogen encompasses qi turbidity， phlegm turbidity， stasis turbidity， and toxin turbidity， closely related to dietary indiscretion， emotional disharmony， spleen-stomach deficiency， and kidney deficiency failing to consolidate. Turbid pathogen undergoes a dynamic evolution process of qi constraint generating turbid→ phlegm-stasis transforming into toxin→turbidity toxin harming the healthy qi， corresponding to the pathological alterations of hypoxia， inflammation and immunosuppression within the tumor microenvironment. The overall therapeutic principle is to remove turbidity and restore clarity. In the early stage， targeting the hypoxic tumor microenvironment， the suggested treatment method is opening constraint and dispersing the block， regulating qi and remove turbidity， with emphasis on soothing liver and regulating stomach， raising the clear and directing the turbid downward. In the middle stage， targeting inflammatory microenvironment， the treatment aims to clear toxin and dissipate nodules， resolve stasis and eliminate turbid， emphasizing phlegm-stasis elimination， turbid-toxin resolution， and concurrent stomach qi protection. In the late stage， corresponding to immunosuppressive microenvironment， the method of boosting qi， nourishing yin， reinforcing healthy qi， and eliminating turbidity can be used， with focus on spleen-stomach tonification， kidney essence replenishment， and healthy qi reinforcement to expel pathogenic factors.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

Objective: To investigate the trend in disease burden of injuries among children and adolescents in China from 1990 to 2021, so as to provide a basis for formulating prevention and control strategies and reducing this disease burden. Methods: Data on mortality, disability-adjusted life years (DALY) rate, incidence, and prevalence of injuries among children and adolescents aged <20 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. All rates were standardized using the GBD 2021 world standard population. The trend in incidence of disease burden of injuries among children and adolescents across differents genders and ages from 1990 to 2021 was evaluated using average annual percent change (AAPC). Results: From 1990 to 2021, the standardized mortality (AAPC=-5.435%), standardized DALY rate (AAPC=-5.311%), standardized incidence (AAPC=-0.466%), and standardized prevalence (AAPC=-0.810%) of injuries among children and adolescents in China showed downward trends (all P<0.05). Among these, the standardized mortality of animal contact (AAPC=-9.138%) and the standardized DALY rate of medical side effects (AAPC=-8.389%) decreased at a relatively fast pace, while the standardized incidence of falls (AAPC=0.083%) and the standardized prevalence of exposure to natural forces (AAPC=2.656%) showed upward trends (all P<0.05). The standardized mortality, standardized DALY rate, standardized incidence and standardized prevalence of injuries were higher in males than in females. The trend in males showed a downward trend (all P<0.05), consistent with the total population. The crude incidence of injuries in the group aged 15-<20 years showed an upward trend (AAPC=0.391%, P<0.05), while the trend in the group aged 10-<15 years was not statistically significant (P>0.05). The crude incidence of injuries in the groups aged 5-<10 years and <5 years showed downward trends (AAPC=-0.488% and -2.275%, both P<0.05). In 2021, the <5 years age group had the highest crude mortality and crude DALY rate of injuries, at 13.94/100 000 and 1 257.26/100 000, respectively. The 15-<20 years age group exhibited the highest crude incidence and crude prevalence, at 4 874.05/100 000and 4 050.35/100 000, respectively. Drowning and falls were major components of the disease burden across all age groups. Conclusions From 1990 to 2021, the disease burden of injuries among children and adolescents in China showed an overall downward trend. The disease burden was consistently higher in males than in females. Children aged <5 years face a high risk of fatality and disability, while adolescents aged 15-<20 years experience a high incidence and frequency of injuries. Drowning and falls were key priorities for prevention and control.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.