The prescription Mahuang Shengmatang in the Treatise on Cold Damage （《伤寒论》） has sparked considerable debate among medical practitioners throughout history， with varying opinions on its indications， pathogenesis described in the text， principle of compatibility， and clinical applications. Both ancient and modern interpreters of Mahuang Shengmatang often focus on herbal compatibility as a primary approach to deduce the pathogenesis and treatment methods. Building upon this foundation， this paper utilizes herbal dosage as a clue to discern the primary and secondary herbs in the prescription. It further analyzes the principle of compatibility based on herbal indications， summarizing the indications and therapeutic principles of this prescription. Ultimately， it reveals the underlying pathogenesis reflected in the text. The internal closure of heat and toxin leads to the stagnation of Qi， preventing Yang Qi from reaching the extremities and causing cold hands and feet. When the pathogenic Qi finds no outlet， it floods both the upper and lower regions of the body， attacking the throat and causing cough with expectoration of pus and blood， and descending to the large intestine to consume Yin fluids， resulting in persistent diarrhea. Based on this pathogenesis， the paper expands the scope of symptoms and signs associated with the prescription， providing a more detailed portrayal of the applicable patient population and enhancing the basis for clinical prescription references. Additionally， the paper presents considerations on several controversial topics， suggesting that the "lower pulse" described in the text refers to the lower limb arterial pulsation， and the symptoms and signs resemble those of septic shock in modern medicine. Therefore， Mahuang Shengmatang should be categorized as a prescription for treating warm diseases and it is not developed by ZHANG Zhongjing. By employing a detailed discussion on the syndrome， pathogenesis， and clinical application in the texts of Mahuang Shengmatang from the dosage， principle of compatibility， and herbal indications， this paper not only enriches the theoretical foundation of Mahuang Shengmatang but also provides a comprehensive perspective and fresh ideas for understanding its clinical application.

Objective: To describe the prevalence and association of dietary rhythm and depressive symptoms among adolescents, so as to provide a basis for improving unhealthy behavioral habits,and to promote adolescent physical and mental health. Methods: From October to December 2021, a total of 22 868 students were selected from one middle school and high school in urban and rural areas of eight cities, namely, Shenyang, Xuzhou, Shenzhen, Taiyuan, Nanchang, Zhengzhou, Chongqing, and Kunming cities, China, using a combination of purposive sampling and stratified cluster random sampling. A self administered questionnaire was used to assess adolescents dietary rhythm, and the Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Binary Logistic regression model was employed to analyze the associations between adolescent dietary rhythm and depressive symptoms, while the associations between adolescent dietary rhythm and depressive symptoms across gender and physical activity levels were stratified by gender and physical activity levels. Results: The detection rate of depressive symptoms in adolescents was 44.4%. The respective differences in the detection rates of depressive symptoms among adolescents of different genders, physical activity levels, and dietary rhythm disorders were statistically significant ( χ 2=157.51, 105.02, 3 282.50, P <0.01). Taking the low disordered dietary rhythm group as the reference, binary Logistic regression analyses showed that after adjusting for confounding factors such as age, gender，family location, family economic situation, whether only child, parental education level, and learning burden, physical activity levels, depressive symptoms were positively correlated with adolescents in the moderate disordered dietary rhythm group ( OR=2.63, 95%CI =2.45-2.83) and the high disordered dietary rhythm group ( OR=6.38, 95%CI = 5.93- 6.86). In addition, after stratifying by gender, dietary rhythm were positively correlated with depressive symptoms. The moderate disordered group (male: OR=2.62, 95%CI =2.37-2.89, female: OR=2.67, 95%CI =2.40-2.97) and the highly disordered group (male: OR=5.74, 95%CI =5.19-6.35, female: OR=7.11, 95%CI =6.40-7.89) were positively correlated with depressive symptoms. After stratification by physical activity levels, low, moderate and above physical activity levels among adolescents in the disordered dietary rhythm group (low physical activity: OR=2.91, 95%CI =2.58-3.29, moderate and above physical activity: OR= 2.50, 95%CI =2.28-2.74), high disordered group (low physical activity: OR=6.51, 95%CI =5.94- 7.13 , moderate and higher physical activity: OR=6.18, 95%CI =5.47-6.97) were positively associated with depressive symptoms ( P <0.01). There was an interaction between dietary rhythm and physical activity levels in regard to the development of depressive symptoms in adolescents, taking the group with moderate and above physical activity levels and low disordered dietary rhythm as the reference,the detection rate of which was higher in adolescents with low levels of physical activity and those in the moderate or high disordered dietary rhythm group ( OR=1.50, 3.90, 95%CI=1.39-1.61, 3.63-4.19, P <0.01). Conclusions Dietary rhythm disorders were found to be positively associated with depressive symptoms in adolescents. Regular dietary behaviors and increased physical activity play an important positive role in promoting adolescent mental health.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

Objective To investigate the effect and potential mechanism of early exercise intervention on cerebral myelin in cerebral ischemia rats.Methods A total of 18 SD rats were randomly divided into the sham group,the middle cerebral artery occlusion resting group(MCAO-SED)and the middle cerebral artery occlusion exercise group(MCAO-EX),with 6 rats in each group.Except the sham group,the middle cerebral artery occlusion model was prepared by modified Longa line embolization method in other groups.After modeling,rats in the MCAO-EX group were placed on a treadmill for exercise intervention for 28 days.Neurological function was assessed by modified neural function deficit score(mNSS).Infarct volume was detected by MRI scanning(T2),myelin basic protein(MBP)expression was detected by immunofluorescence.Myelin sheath structure was detected by transmission electron microscopy.Western blot assay was used to detect endoplasmic reticulum stress-related protein expression.Apoptosis was detected by TUNEL staining.Results After 28 days of intervention,compared with the MCAO-SED group,the nerve function recovered well in the MCAO-EX group,infarct volume decreased,myelin integrity increased,MBP fluorescence intensity expression increased and MBP expression level increased.The expression levels of ATF6,p-IRE1,p-PERK and cleaved caspase 3 were significantly decreased,and apoptosis was reduced.Conclusion Early exercise can inhibit endoplasmic reticulum stress-induced apoptosis,promote cerebral myelin repair,reduce infarct size and improve nerve function.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective: The aim of this study was to establish a comprehensive concise health index (CHI) for evaluating adolescents, so as to provide a basis for determining the overall health status of adolescents in China. Methods: On the basis of a literature review and consensus among core researchers, adolescent CHI indicators in the following five dimensions were assessed:physical growth, physical fitness, common diseases, mental health and behavioral health. A total of 24 experts used an analysis hierarcgy process (AHP) to calculate the indicators subjective weights. In addition, from October to December of 2021, two regions, A and B were selected to conduct empirical research, and the CRITIC method was used to calculate the objective weights of the indicators. Finally, the weight coefficients were determined through the AHP-CRITIC combination weight method, and comprehensive evaluation was performed with the TOPSIS method. Results: Across academic period and genders, the combined weighted coefficients of the health indicators were as follows:BMI, 0.081-0.095; waist circumference, 0.070-0.081; relative grip strength, 0.101-0.108; myopia, 0.110-0.128; dental caries, 0.055-0.070; psychological symptoms, 0.240-0.262; physical exercise, 0.085-0.115; screen time, 0.097-0.111; and sleep duration, 0.086-0.103. The health index of middle school students in city A (0.626±0.065) was significantly higher than that in city B(0.613±0.066)( t=6.34, P <0.01). Conclusion The comprehensive adolescent CHI evaluation method has good consistency and application value, and may serve as a reference for adolescent health monitoring.

Objective: To develop a simplified Rating Questionnaire of Social Ecological Risks in Adolescents and to evaluate the reliability and predictive validity of the brief questionnaire, so as to provide data and evidence support for building the evaluation system of cumulative social ecological risk exposure. Methods: A large cross sectional was conducted in eight areas, including Shenzhen, Zhengzhou, Xuzhou, Nanchang, Shenyang, Taiyuan, Kunming and Chongqing, from October to December 2021. A total of 22 868 adolescents were included in the analysis. Data on healthy behaviors from 10 838 adolescents from Shenyang, Taiyuan, Kunming, Chongqing were used for item selection, based on factor analysis, validity and reliability evaluation. The data from Shenzhen, Zhengzhou, Xuzhou, Nanchang, including 12 030 adolescents, were used to define the partition values of the brief questionnaire, and evaluate the predictive validity. Results: The brief questionnaire containing 25-item were developed by analyzing and choosing all items of original questionnaire, and covered seven dimensions including individual, family, school, community, policy, time and culture. The cumulative contribution rate of variance was 54.95%, the Cronbach coefficient was 0.79, and the split half coefficient was 0.70. Participants in the higher risk group had significantly higher risk of smoking ( OR =4.05, 95% CI = 2.78 -5.92), drinking ( OR =3.47, 95% CI =2.86-4.19), suicidal ideation ( OR =8.85, 95% CI =7.68-10.21), suicidal plans ( OR = 8.85, 95% CI =7.27-10.78), suicidal attempt ( OR = 8.86 , 95% CI =6.67-11.78) than individual in the lower risk group ( P < 0.05). After stratified by gender, the above positive correlations still remained significant( P <0.05). Conclusion The brief questionnaire, with good reliability and predictive validity, could be widely applicated in the further researches on social ecological risk factors.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

ObjectiveTo investigate the mediating role of loneliness and social anxiety in the relationship between basic psychological needs satisfaction and smartphone addiction among high school students， and to provide references for the intervention to smartphone addiction for high school students. MethodsIn April 2022， a total of 14 666 high school students from 5 middle schools in a county of Sichuan Province were included by random sampling method. Basic Psychological Needs Scales （BPNS）， the UCLA Loneliness Scale-3 edition （UCLA-3）， Interaction Anxiousness Scale （IAS） and the Mobile Phone Addiction Index （MPAI） were used for cross-sectional investigation. Bootstrap method was used to analyze the mediating role of loneliness and social anxiety in the relationship between the basic psychological needs satisfaction and smartphone addiction. Results① In this study， 14 036 valid questionnaires were returned， and 1 752 （12.48%， 95% CI： 0.114~0.136） high school students were found to be addicted to smartphone phone. The BPNS score was negatively correlated with UCLA-3， IAS and MPAI scores （r=-0.771， -0.486， -0.417， P<0.01）. And MPAI score was positively correlated with IAS and UCLA-3 scores （r=0.403， 0.424， P<0.01）. IAS score was positively correlated with UCLA-3 score （r=0.458， P<0.01）. ②The degree of basic psychological needs satisfaction in high school students can directly negatively predict smartphone addiction （β=-0.383， P<0.05）， and can also indirectly affect smartphone addiction through loneliness and social anxiety （β=-0.130， P<0.05）. ③Loneliness （indirect effect value was -0.145） and social anxiety （indirect effect value was -0.074） partially mediate between the basic psychological needs satisfaction and smartphone addiction. Loneliness-social anxiety also has significant chain mediating effect （indirect effect value was -0.034）， which accounted for 8.88%. ConclusionThe basic psychological needs satisfaction can not only directly affect the occurrence of smartphone addiction， but also indirectly affect the occurrence of smartphone addiction through the chain mediation of loneliness and social anxiety.

Objective: To analyze the association between non-school sedentary time and myopia among primary and secondary school students with different levels of physical activity, so as to provide data for precise measures to prevent and control myopia. Methods: From September to December 2019, stratified cluster sampling was used to select 7 872 primary and secondary students in grades 4 to 12, middle and high school students from Hefei, Suzhou, Chizhou and Wuhu Cities in Anhui Province. Face-to-face questionnaires and vision examinations were conducted to collect demographic information, physical activity time, sedentary study time and visual health status. Potential categories were analyzed for different types of physical activity time, and Logistic regression was used to assess the relationship between non-school sedentary time and myopia at different levels of physical activity. Results: A total of 2 976 primary and secondary school students were found with high physical activity levels and 4 896 primary and secondary school students with low physical activity levels. The proportion of low physical activity was higher in girls than in boys (68.7% vs . 55.6%), and the differences were statistically significant ( χ 2=143.97, P <0.01). The overall screening myopia rate was 48.2%, with statistically significant differences among female students (53.0%) compared with male students (43.3%), urban students ( 51.8 %) compared with rural students (44.5%), and longer non-school sedentary time students (60.6%) compared with average (45.1%) and shorter (42.1%) non-school sedentary time students, and the differences were statistically significant ( χ 2=73.15, 41.96 , 161.74, P <0.01). Adjusting for confounders such as residence, grade, gender, age, father s education, mother s education, and body mass index (BMI), multivariate Logistic regression analysis revealed that prolonged after-school sedentary study was positivety correlated with myopia among primary and secondary school students of low physical activity levels ( OR=1.52, 95%CI=1.27-1.83, P <0.01), and there was no statistical association between after-school sedentary time and myopia in primary and secondary school students with high physical activity levels ( P >0.05). Conclusion Attention should be paid to non-school sedentary time for primary and secondary school students with low physical activity levels. And students who spend a lot of time sitting outside of school should be encouraged to maintain high physical activity levels to reduce the risk of myopia.