Objective To genetically investigate the protective effects of statins on breast cancer. Methods Instrumental variables for the statin target gene HMGCR and five other cholesterol-regulated genes (LDLR, PCSK9, ABCG8, APOB, and NPC1L1) were obtained from previous expression quantitative trait locus (eQTL) studies. Cholesterol-regulated genes predicted by these instrumental variables served as the exposure factors. Mendelian randomization based on pooled data (SMR) was conducted to explore the genetic effects of exposure factors on the incidence risk of all breast cancers, ER+ breast cancer, and ER-breast cancer. Instrumental variables for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) were derived from a previous human genome-wide association study and restricted to be chromosomally located within 100 kb of the above cholesterol regulatory genes; the instrumental variables could predict TC, LDL-C, or non-HDL-C levels under the regulation of the abovementioned cholesterol-associated genes which were used as exposure factors. Two-sample Mendelian randomization (IVW, MR-PRESSO, and MR-Egger) was used to explore the genetic effects of exposure factors on the risk of all breast cancers, ER+ breast cancer, and ER− breast cancer. Results SMR analysis reported that elevated HMGCR expression was significantly associated with the increased incidence risk of all breast cancers and ER+ breast cancer (P=0.044 and P=0.039, respectively) but not with the change in incidence risk of ER− breast cancer (P=0.190); the other five regulatory genes were not significantly correlated with the change in incidence risk of all breast cancers, ER+ breast cancer, and ER− breast cancer (all P>0.05). IVW analysis reported that under the regulation of HMGCR, elevated levels of peripheral TC, LDL-C, and non-HDL-C significantly increased the incidence risk of all breast cancers (P=1.160e-05, P=1.248e-05, and P=1.869e-05) and the incidence risk of ER+ breast cancer (P=3.181e-04, P=2.231e-04, and P=3.520e-04), but they were not associated with a change in the incidence risk of ER− breast cancer (P=0.062, P=0.133, and P=0.055). The results of MR-PRESSO and MR-Egger analyses supported the IVW results. Conclusion Statins could reduce the incidence risk of ER+ breast cancer at the genetic level, but there is no such protective effects on ER− breast cancer.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

Pinellia ternata， belonging to the Pinellia genus within the Araceae family， is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation， necessitating urgent new variety protection efforts. The distinctness， uniformity， and stability （DUS） testing of the plant variety is the basis for protecting new plant varieties， and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata， agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years， and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits， 19 leaf traits， six flower traits， two fruit traits， two tuber traits， five bulbil traits， and one ploidy trait. These traits could be divided into 22 quality characters， 12 quantitative characters， and four pseudo-quantitative characters， as well as seven groups， including plants， leaves， flowers， fruit， tubers， bulbils， and ploidy. By searching for standard traits， 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties， safeguarding breeders' rights， and promoting the development of the P. ternata industry.

ObjectiveA multiplex amplification system was constructed based on the capillary electrophoresis platform for simultaneous detection of saliva, semen, and vaginal secretions using tissue-specific RNA markers. The aim of this study is to identify the tissue origin of suspicious body fluid stains found at crime scenes and determine whether the body fluid stains at the crime scene are one or several types among saliva, semen, and vaginal secretions. MethodsThirty saliva samples, forty semen samples, and forty vaginal secretion samples (half from 2015 and half from 2024) were collected from healthy adult volunteers. Through primer designing, system formulation, and PCR condition optimization, a multiplex fluorescent amplification system was constructed. The specificity, sensitivity, and detection ability for mixed samples of this system were investigated, and it was tested using real crime scene materials. In the primer design stage, to reduce the requirements for RNA template quality, the amplification products were set within 80-300 bp. In the system formulation stage, dominant and subordinate primers were mainly considered. By reducing the concentration of dominant primers and increasing that of subordinate primers, a capillary electrophoresis spectrum with an appropriate peak height ratio was finally obtained. Additionally, gradient experiments were designed to adjust the concentrations of PCR reagents and PCR amplification conditions, and multiple versions of DNA amplification enzymes were optimized to achieve the best experimental results. ResultsThrough statistical analysis, there was no significant difference in the capillary electrophoresis of the 3 types of body fluid samples from the two years (2015 and 2024), demonstrating that the sample preservation method in this study can preserve samples for a relatively long time. The composite amplification system constructed in this study exhibited high specificity for all 3 types of body fluid, with no cross-reactions between the markers of each type of body fluid. The minimum detection thresholds for the 3 types of body fluid reached 0.002 9, 0.001 5, and 0.42 mg/L, respectively. This system also had a high degree of discrimination for mixed samples, especially for semen-saliva mixtures, where each body fluid marker could still be successfully detected when the concentration ratio of semen to saliva was 100:1. Meanwhile, in the two actual cases presented in this article, the application of this composite amplification system performed outstandingly. ConclusionThe composite amplification detection system constructed in this study can achieve the correct screening of saliva, semen, and vaginal secretions, overcoming the problems such as low specificity and sensitivity of marker tests and unbalanced RFU values of each marker in previous studies. The specificity and sensitivity meet the practical work requirements, and the operation is simple. It provides an analytical and identification method for body fluid stains in actual case and is applicable to the identification of the tissue origin of biological evidence at crime scenes involving sexual assault, indecent assault, and other criminal acts. In the future, more types of body fluid markers will be screened to expand the types of body fluids detected by the system, and body fluid-specific cSNP and cInDel genetic markers will be introduced to infer the sources (individuals and types) of mixed and complex stains more accurately.

Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy， reasoning， deduction， and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind， fire， phlegm， and blood stasis" in stroke， thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile， the article traced the construction process of xiang thinking， and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives， state， attribute， origin， and law. Furthermore， the relationship between the process of constructing xiang thinking and the origin of etiology， identification methods， pathogenesis evolution， and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored， so as to provide insights into research on the etiology and pathogenesis of stroke， as well as clinical diagnosis and treatment approaches.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.