Cold-heat problem is one core of traditional Chinese medicine theory. This paper summarizes the experimental research related to the biological basis of cold-heat essence in cold-heat syndrome, cold-heat body constitution and cold-heat property of Chinese herbs. In view of the classical physiological and biochemical indices, gene expression, protein expression and metabolic differences, differences in cold-heat syndrome or cold-heat constitution are mainly based on neurotransmitter, thyroid function, sex hormone, cyclic nucleotide system, and energy metabolism relating to the corresponding gene and protein expression. Furthermore, this paper analyses the change of correlation indices that accompany with a dynamic development process of "constitution-syndrome-herbal intervention", implying that the research of biological basis of cold-heat essence has turned from single index to multiple indices, and from dispersion research to system research.

Objective:To investigate the efficacy differences between domestic gefitinib and original gefitinib in the first-line treatment of patients with epidermal growth factor receptor (EGFR) sensitive mutation advanced non-small cell lung cancer (NSCLC) (stage Ⅲ B and Ⅳ). Methods:A total of 91 cases with EGFR sensitive mutation advanced NSCLC in Dezhou People's Hospital of Shandong Province from January 2017 to July 2019 were selected and were randomly divided into the observation group (47 cases) and the control group (44 cases) according to random number table method. The observation group was given the treatment of domestic gefitinib, and the control group was given the treatment of original gefitinib, and then the treatment outcome, adverse reactions, survival status and the cost of two groups were compared.Results:The objective response rate in the observation group and the control group was 91.5% (43/47) and 84.1% (37/44), respectively; the disease control rate in the observation group and the control group was 100.0% (47/47) and 97.7% (43/44), respectively; and the differences were not statistically significant ( χ2 = 2.708, P = 0.224; χ2 = 1.080, P = 0.484). The median progression-free survival (PFS) time of domestic gefitinib group and original gefitinib group was 13.26 months (95% CI 11.34-14.66 months) and 13.19 months (95% CI 12.52-15.48 months), respectively, and the difference was not statistically significant ( P = 0.735). The subgroup analysis showed that the median PFS time of patients with an exon 19 deletion mutation in the observation group and the control group was 12.98 months (95% CI 11.25-14.75 months) and 13.89 months (95% CI 12.04-15.96 months), respectively, and the difference was not statistically significant ( P = 0.604). The median PFS time of patients with an exon 21 L858R missense mutation in the observation group and the control group was 15.08 months (95% CI 11.79-18.21 months) and 11.94 months (95% CI 9.20-14.79 months), and the difference was not statistically significant ( P = 0.114). There was no statistically difference in the incidence of adverse reactions including skin rash, diarrhea, interstitial pneumonia, oral mucositis, nausea and vomiting, myelosuppression, abnormal aminotransferase of the two groups of patients (all P > 0.05). The treatment cost in the observation group and the control group during the treatment period was (2 118.43±137.93) yuan per month and (5 945.48±247.48) yuan per month, respectively, and the difference was statistically significant ( t = 12.854, P = 0.001). Conclusions:Domestic gefitinib and original gefitinib have the same therapeutic efficacy in the treatment of EGFR sensitive mutation advanced NSCLC. The adverse reactions are similar between domestic gefitinib and original gefitinib. Compared with the original gefitinib, the drug economy of domestic gefitinib is better and it can significantly reduce the financial burden of patients, and it can be used as an important option in the first-line treatment of patients with EGFR sensitive mutation advanced NSCLC.

Objective: To investigate the dietary lead exposure level among children aged 3 to 4 years in Jiading District, Shanghai Municipality, and assess the health risk caused by lead exposure, so as to provide the basis for the management of children's food safety. Methods: Based on the 2023 Dietary and Health Status Surveillance Project in Jiading District, children aged 3 to 4 years from 12 streets (townships) in Jiading District were selected as the subjects using a multi-stage stratified random sampling method. The consumption frequency and daily intake of seven subcategories of four major food groups (beans, tofu), cereals (wheat, rice), meat (animal viscera), and aquatic products (mantis shrimps, bivalves) consumed by children over the past three months were collected using a food frequency questionnaire. Food samples were collected according to the food safety risk monitoring plan in Jiading District, and the lead content was detected. The health risks of dietary lead exposure among 3-4-year-old children were quantitatively assessed using the single-factor pollution index method, the Nemerow comprehensive pollution index method, and the margin of safety (MOS) method. Results: A total of 143 3-4-year-old children were surveyed, including 69 boys (48.25%) and 74 girls (51.75%). A total of 317 food samples were tested, and lead was detected in all seven subcategories of food samples, with an overall detection rate of 77.29%. The detection rates of lead in bivalves and mantis shrimps of aquatic products were relatively high (98.75% and 100.00%, respectively). The mean lead content of various foods ranged from 0.003 4 to 0.090 7, with the highest level found in bivalves. The lead content of all food samples did not exceed the standard. The single-factor pollution index of seven subcategories ranged from 0.017 2 to 0.148 0, and the Nemerow comprehensive pollution index ranged from 0.116 5 to 0.424 4, both of which were less than 0.7. The MOS (mean) ranged from 0.000 3 to 0.003 9, with an overall MOS (mean) of 0.012 2. The MOS (P95) ranged from 0.005 7 to 0.055 9, with an overall MOS (P95) of 0.112 4, both of which were less than 1. Conclusions The lead pollution level in the diet among children aged 3 to 4 years in Jiading District is safe and clean, with an acceptable impact on food safety. However, the detection rate of lead is relatively high, and the main source of dietary lead exposure is aquatic products.

Objective:To study the effects of ascorbic acid on BMP-2 mRNA expression of osteoblast cell sheets.Methods:Rat os-teoblasts were primaryly cultured and identified;osteoblast cell sheets were built by physical scraping method in vitro;the osteoblast cell sheets were cultured with 1 5,50 and 85 mg/L ascorbic acid for 1 and 2 weeks respectively,and the expression of BMP-2 mRNA of the cell sheets was detected by RT-qPCR.Results:The obtained cells were conformed to be osteoblasts.The osteoblast cell sheets could be rolled into tube in vitro.The expression of BMP-2 mRNA of osteoblast cell sheets in experiment group,whether in week one or week two was higher than that in control group,50 mg/L group showed the highest expression(first week P <0.05;second week P>0.05);the expression of any group in week two was higher than that in week one(P <0.05).Conclusion:Ascorbic acid may pro-mote the expression of BMP-2 mRNA in osteoblast cell sheets.

Objective To study the relationship between Y chromosome abnormalities and AZF microdeletions in males with reproductive failure.Methods A case-control study was conducted in 2694 reproductive failure men with age ranges from 23 to 49 years old from the Institute of Reproductive Medicine of Jilin Province.Patients were divided into three groups:spermatogenic failure group (n =1332),disadvantage pregnancy outcomes group (n =994) and adverse birth outcomes group.All patients underwent chromosomal karyotype analysis (G-banding).AZF microdeletions were further investigated in patients with Y chromosomal abnormalities by PCR.The Chi-square test was used to compare the frequency of Y chromosome abnormalities in three groups.Results Of the 51 cases of Y chromosome abnormalities (1.89％,51/2694),32 were (2.40％,32/1332) in the spermatogenic failure group,15 were (1.51％,15/994) in disadvantage pregnancy outcomes group and 4 were (1.09％,4/368) in adverse birth outcomes group.There was no significant difference in Y chromosome abnormalities among different groups (x2 =3.895,P ＞0.05).AZF microdeletions were detected in 10 cases (19.61％,10/51) of Y chromosome abnormalities patients with spermatogenic failure.Conclusions The incidence of Y chromosomal abnormalities in three reproductive failure groups is similar.Chromosome karyotype analysis and AZF microdeletions examination could identify the genetics etiology in males with reproductive failure.

Objective To describe different types of chromosomal abnormalities on male infertility.Methods From May 2006 to May 2012,2034 infertile males with genetic counseling underwent chromosome karyotype analysis,semen routine examination and reproductive hormones levels detection.The data from them were analyzed.Results 267 cases of chromosomal abnormalities were detected in 2034 cases (13.13％).258 cases underwent semen routine examination in 267 cases with chromosomal abnormalities,of which 190 cases of azoospermia,58 cases of oligozoospermia,10 cases of semen normal.In 267 cases of chromosomal abnormalities,including 169 cases (63.30％) of number abnormalities,mainly with azoospermia,157 cases of Klinefelter syndrome (KS) (58.80％),7 cases of 47,XYY (2.62％),4 cases of Turner syndrome (1.50％),1 case of marker chromosome (0.37％) ; 49 cases (18.35％) of structural abnormalities mainly with oligozoospermia,including 32 cases of chromosomal translocations (11.99％),17 cases of inversion (6.37％) ; 4 cases of sex reversal (1.50％) with azoospermia; 45 cases of chromosome polymorphism (16.85％) mainly with oligozoospermia.Non-mosaicism KS patients' age,testicular volume,semen volume,and serum reproductive hormones levels were compared between different groups of semen results,and there were no significant difference except age.Conclusions Chromosome abnormalities were the most important genetic causes of abnormal semen quality and male infertility.It is necessary to be performed chromosome karyotype analysis for infertile males.

Objective To study the relationship between small Y and azoospermia factor (AZF)microdeletions and the effect on male infertility.Methods Data of 379 infertile males of chromosomal karyotype analysis from May 2010 to October 2011 were investigated.Patients with small Y chromosome were also performed C banding and AZF microdeletions,and their fathers and brothers were offered the same examinations.Results Eight patients were small Y chromosome,and their fathers or brothers' chromosome karyotypes were consistent with the probands.Among the 8 cases,there were 3 patients with AZF microdeletions,while their fathers and brothers didn't have microdeletions.Another 5 cases of small Y and their fathers did not exist AZF microdeletions.Conclusions The small Y karyotype is not the key factors that cause male infertility.The reason for infertile patients with small Y and AZF microdeletions was maybe the microdeletions.However,patients with small Y but without AZF microdeletions are not important to male infertility.

Objective:To investigate the stress distribution in peri-implant bone with All-on-4 implant with various parameters by three-dimensional finite element method.Methods:An edentulous mandibular specimen was scanned by CT Mimcs.Geomagic,Uni-graphics,HyperMesh modeling software were used to establish All-on-4 implant finite element models with different inclination angles and corresponding cantilever lengths.1 50 N vertical static load was applied at the right end of the cantilever,peri-implant bone stress was analysed using Abaqus software.Results:When the distal implant inclined 0°with cantilever length of 1 9.5 mm,the peak stress in peri-implant cortical bone at the mesial and distal side was 25.526 MPa and 83.026 MPa respectively.When the distal implant in-clined 1 5°,30°and 45°with the cantilever length of 1 7.2 mm,1 3.3 mm and 9.8 mm,the stress in perio-implant cortical bone at distal side of the implant reduced by 1 2.4%,35.6% and 53.1 %,that at mesial side of the implant reduced by 1 3.6%,36.3% and 40.2%,respectively.Conclusion:From the perspective of the stress analysis,the design of All-on-4 distal implant with large incli-nation angle and short cantilever is superior to that with small inclination angle and long cantilever.

Objective To analyze the quality control measures on urinary fluoride testing in the implementation,and to provide experience in quality control for testing activities.Method According to the Determination of Fluoride in Urine-Ion Selective Electrode Method (WS/T 89-1996),focusing on ways to complete testing all the samples in a short time,implementing internal quality control measures in the testing before,during and after the implementation by different ways as blank experiment,standard substance detection,personnel parallel experiment,paralleled detection,instrument comparison and sample test repeat,were carried out.Results The test results of blank experiment were lower than the lowest detection limit;the test results of standard material were within the scope of the standard reference,there was no significant difference between the mean value and the reference value (t =0.01,0.00,0.02,all P ＞ 0.05),|Z| values were all less than 1;the results of personnel parallel experiment,paralleled detection,instrument comparison test results and sample test repeat were not significantly different statistically (all P ＞ 0.05);the results of instrument comparison and sample test repeat were not significantly different statistically (t =0.129,0.034,all P ＞ 0.05).A total of 9 123 urine samples were tested,the geometric mean of urinery fluoride was 0.58 mg/L.Conclusion Different quality control measures should be implemented through all the testing,control personnel errors,instruments,and reagents,etc,to ensure the quality of the entire test results.

Objective To explore humor experience and its relationship with theory of mind in patients with schizophrenia. Methods sixty?one schizophrenic patients without treatment and sixty?three healthy subjects were assessed with the Humor Picture Test ( HPT) ,Humor Video Test ( HVT) and the Theory?of?Mind Picture?Se?quencing Task ( ToM?PST) . Results Compared with healthy subject in HPT,schizophrenic patients showed sig?nificantly higher non?humor picture rating score (24.41 ± 8.82 vs 28.41 ± 11.56, P<0.05),and less humor picture rating score (45.65 ± 11.49 vs 34.41 ± 13.06, P<0.05). Compared with healthy subject in HVT,schizophrenic patients also showed significantly less humor video rating score (3.56 ± 0.57 vs 2.46 ± 0.79, P<0.01) and the number of standard humorous moments (3.68 ± 1.19 vs 2.42 ± 1.40, P<0.01) and the sensitivity of standard hu?morous moments?d’(humor) score (1.11 ± 0.46 vs 0.47 ± 0.42, P<0.01). Schizophrenic patients had significant?ly less total score (39.89 ± 12.33 vs 58.76 ± 0.64, P<0.01) of ToM?PST compared to normal control. Correlation analysis showed a negative correlation between d’ ( humor) score and the Positive and Negative Syndrome Scale ( PANSS) total score ( r=-0.380, P<0.01) for the patients. There was significantly negative correlation between non?humor picture rating score and ToM?PST total score ( r=-0.316, P<0.05) ,and positive correlation between d’ (humor) score and ToM?PST total score ( r=0.400, P<0.01) in schizophrenic patient. After controlling for the PANSS total score,the correlation between d’(humor) score and ToM?PST total score remained significant. Conclusion Schizophrenic patients have poor humor experience,which is related to the impairments of theory of mind.Humor experience deficit may share a common neuropsychological base with the impairment of theory of mind.