Objective To study the medication law of Professor Zhang Yunling in the treatment of headache based on data mining technology;To provide ideas for the clinical treatment of headache.Methods Professor Zhang Yunling's outpatient TCM prescription data for the treatment of headache from Sep.2017 to Dec.2020 were collected,and the Ancient and Modern Medical Record Cloud Platform 2.3.5 was used to mine the selected TCM prescriptions for herbal medicine frequency statistics,property,taste and meridian tropism statistics,herbal medicine efficacy statistics,correlation analysis,clustering analysis,complex network analysis,etc.Results Through collection and screening,totally 332 prescriptions were included,involving 178 kinds of Chinese materia medica,with a total frequency of 5 380 times.The top 10 kinds of Chinese materia medica were Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Testudinis Carapax et Plastrum,Bambusae Caulis in Taenia,Glycyrrhizae Radix et Rhizoma,Astragali Radix,Amomi Fructus Rotundus,Pinelliae Rhizoma Praeparatum,and Polygalae Radix.They were mainly warm,mild and slightly cold in properties,sweet,pungent and bitter in tastes,and liver,lung,spleen meridian in meridian tropism.In the statistics of herbal medicine efficacy,expelling wind and relieving pain,suppressing liver yang,promoting blood circulation and qi,clearing heart and relieving restlessness,clearing heat and detoxifying,softening liver and relieving pain were used more frequently.The combinations in herbal medicines association included"Atractyodis Macrocephalae Rhizoma-Chuanxiaong Rhizoma","Testudinis Carapax et Plastrum-Paeoniae Radix alba","Glycyrrhizae Radix et Rhizoma-Paeoniae Radix alba","Testudinis Carapax et Plastrum-Chuanxiaong Rhizoma","Bambusae Caulis in Taenia-Chuanxiaong Rhizoma".Herbal medicines clustering clustered 32 kinds of high-frequency herbal medicines used more than 60 times into 6 categories.Complex network analysis screened out the core formula for the treatment of headache:Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Bambusae Caulis in Taenia,Pinelliae Rhizoma Praeparatum,Testudinis Carapax et Plastrum,Astragali Radix,Amomi Fructus Rotundus,and Glycyrrhizae Radix et Rhizoma.Conclusion In the treatment of headache,Professor Zhang Yunling holds that the pathogenesis of headache is deficiency in origin and excess in superficiality,deficiency of qi and blood,loss of nourishment of brain collaterals,stagnation of phlegm and dampness,disturbance of wind pathogen,obstruction of brain collaterals,and the location of the disease is related to the five viscera and involves the stomach.Focuses on tonifying deficiency and reducing excess,treats exterior and interior separately,and gives consideration to both the symptoms and the root causes,which often uses drugs to treat headache,such as dispelling wind and relieving pain,promoting blood circulation and relieving pain,relieving spasm and relieving pains,eliminating phlegm and dampness,invigorating qi and spleen,nourishing blood and yin,eliminating dampness and regulating stomach,relieving depression and restlessness,which can provide some reference for the clinical treatment of headache.

Objective The Network Enhancement Fusion(ne-SNF)method had no denoising strategy for the networks from each omics data type,which would weaken the power of network fusion.To address this problem,we proposed an improved Network Enhancement Fusion(improved ne-SNF)model,and further applied the method to subtype identification of papillary renal cell carcinoma.Methods We conducted simulation studies to compare the performances of the improved ne-SNF method with the ne-SNF and SNF method,and applied improved ne-SNF method to integrate multi-omics data of PRCC.Cox regression model was performed to evaluate the prognostic risk of different subtypes.Differentially expressed mRNAs(DEmRNAs),miRNAs(DEmiRNAs)and differentially methylated genes(DMGs)with different subtypes were screened.KEGG pathway analysis was performed for the overlapping genes of three gene sets.Finally,the immune cell infiltration analysis was performed for patients with different subtypes.Results The improved ne-SNF method outperformed both SNF and ne-SNF approach in various simulation scenarios.In subsequent subtyping application,PRCC patients were divided into high-risk and low-risk groups,and the risk of death was 7.727 times higher in the high-risk group than in the low-risk group.A total of 3511 DEmRNAs,96 DEmiRNAs and 3426 DMGs were identified.Among them,649 overlapping genes yielded 42 KEGG pathways with statistical differences.In addition,3 immune filtrating cells showed statistical significance.Conclusion The improved ne-SNF performed better than SNF and ne-SNF,and the identified subtypes of PRCC may provide important clues and basis for treatment of PRCC patient.

Objective:To explore the distribution and characteristics of microbiota in the lower reproductive tract of patients with cervical squamous cell carcinoma infected by human papilloma virus (HPV) 16 subtype.Methods:A prospective, cross-sectional study was conducted. A total of 6 patients with HPV16 single subtype positive cervical squamous cell carcinoma admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from August 2019 to June 2020 were selected as cervical carcinoma group, and 6 healthy women who did not indicate abnormalities in thin-based layer cytology test (TCT) during the same period among the physical examination population and had HPV negative test result were selected as the healthy control group. A sterile cotton swab was used to collect secretions from the posterior cervical fornix in patients before antitumor treatment and healthy controls during physical examination. The high variable region of the 16S rRNA gene V1-V2 of the bacteria was amplified by using next generation sequencing (NGS), and then the distribution and characteristics of the bacteria were analyzed.Results:The age of cervical cancer group and the healthy control group was (51±8) years and (48±3) years, respectively, and the difference in age between the both groups was statistically significant ( t= 0.63, P= 0.540). The patients of both groups had reproductive history and no smoking experience. Alpha diversity analysis showed that compared with the healthy control group, the sobs ( t= 3.25, P= 0.009) and chao ( t= 2.91, P= 0.016) indexes were higher in cervical cancer group, and the differences were statistically significant. The shannon index was higher ( t= 2.07, P= 0.065) and simpson index was lower ( t= 1.74, P= 0.113) in cervical cancer group, while the difference was not statistically different. Data dimensionality reduction analysis in principal coordinate analysis (PCoA) based on bray-curtis distance showed that the difference in Beta diversity between the healthy control group and cervical cancer group was statistically significant ( R2= 0.154, P = 0.018). At the phylum level, the proportion of Firmicutes in cervical cancer group was lower than that in the healthy control group (30.21% vs. 68.28%), while the proportion of Bacteroidetes in cervical cancer group decreased slightly (6.87% vs. 8.11%); and the proportion of Actinobacteria (26.91% vs. 14.42%) and Proteobacteria (27.33% vs. 0.67%) had an increase in cervical cancer group. At the genus level, compared with the healthy control group, the proportion of Lactobacillus and Corynebacterium decreased in cervical cancer group, and loss of dominant flora could be detected; while Rhodococcus, Klebsiella and Aerococcus increased significantly in cervical cancer group. The bacteria species in cervical cancer group was increased compared with the healthy control group. Linear discriminant analysis (LDA) showed that Rhodococcus (LDA = 5.04), Klebsiella (LDA = 4.71), Enterobacter (LDA = 4.29), Ralstonia (LDA = 4.28), Ochrobactrum (LDA = 4.23) and Veillonella (LDA = 4.14) were the distinctive microbiota of cervical cancer group at the genus level. At the phylum level, Firmicutes (LDA = 5.23) in the healthy control group could be considered as a marker species. At the species level, the proportions of Rhodococcus ( P = 0.025), Ralstonia ( P = 0.045), Veillonella ( P = 0.044), Paraburkholderia ( P = 0.045), Pseudomonas ( P = 0.043) in cervical cancer group were increased compared with the healthy control group, and the differences were statistically significant. Conclusions:HPV16 single positive patients with cervical squamous cell carcinoma show the characteristics such as the increased diversity and richness of the lower reproductive tract microbiota compared with the healthy controls, while the abundance of Lactobacillus decreases. Rhodococcus and Klebsiella could serve as symbolic microbial in the lower reproductive tract. However, further studies still need to be verified.

ObjectiveTo explore the medication rules of traditional Chinese medicine compounds for depression in the National Patent Database using data mining， and to provide ideas for the clinical treatment and the development of new drugs for depression. MethodsThe patent data of traditional Chinese medicine compounds for the treatment of depression were searched from inception to July 1st， 2022 on the Patent Publication Announcement website of China National Intellectual Property Administration. The selected traditional Chinese medicine compounds were analyzed by using the data mining section of the ancient and modern medical record cloud platform （V2.3.5） for drug frequency， and based on this， the nature， flavor， channel entry and function of the medicinals were analyzed. Representative high-frequency herbal combinations were obtained through correlation analysis， while the classification of Chinese medicine compounds for depression was analyzed by cluster analysis， and the core combinations of herbs for the treatment of depression were screened out using complex network analysis. ResultsA total of 325 Chinese medicine compounds were included， involving 452 herbs， with a total frequency of 3532 times. The top 10 mostly used herbs were Yujin （Radix Curcumae， 122 times）， Chaihu （Radix Bupleuri， 122 times）， Baishao （Radix Paeoniae Alba， 109 times）， Suanzaoren （Spina Date Seed， 95 times）， Fuling （Poria， 94 times）， Danggui （Radix Angelicae Sinensis， 94 times）， Yuanzhi （Radix Polygalae， 84 times）， Baizhu （Rhizoma Atractylodis Macrocephalae， 72 times）， Shichangpu （Rhizoma Acori Graminei， 71 times）， and Danshen （Salvia Miltiorrhiza， 61 times）. The natures of the herbs were mainly warm （998 times）， neutral （944 times）， slightly cold （596 times） and cold （497 times）； the flavors were mainly sweet （1648 times）， acrid （1392 times）， and bitter （1337 times）； the channels of entry were mainly liver （1695 times）， heart （1521 times）， spleen （1326 times） and lung （1268 times）. The medicinals with the function of soothing liver to relieve constraint， moistening the intestines to promote defecation， calming the heart and the mind， moving qi to relieve constraint were used more frequently. The high frequency herbal combinations by association analysis included “Chaihu （Radix Bupleuri）→ Baishao （Radix Paeoniae Alba）”， “Danggui （Radix Angelicae Sinensis）→Chaihu （Radix Bupleuri）” and “Baishao （Radix Paeoniae Alba）→ Yujin （Radix Curcumae）”. The 22 high frequency medicinals used more than 40 times could be clustered into six categories. Complex network analysis found the core herbal combination for the treatment of depression was the formula of Chaihu （Radix Bupleuri）， Yujin （Radix Curcumae）， Baishao （Radix Paeoniae Alba）， Danggui （Radix Angelicae Sinensis）， Fuling （Poria）， Suanzaoren （Spina Date Seed）， and Xiangfu （Cyperi Rhizoma）. ConclusionTraditional Chinese medicine compounds for the treatment of depression is mainly based on the pathogenesis of constraint， stasis and deficiency， focusing on the liver， heart， spleen and lung， commonly using medicinals with the function of soothing liver to relieve constraint， fortifying spleen and nourishing heart， regulating qi and invigorating blood， and moistening the intestines to promote defecation， which can provide a reference for the clinical treatment and new drug research and development for depression.

As the guiding theory for the diagnosis and treatment of encephalopathy in traditional Chinese medicine （TCM）， The marrow sea theory has important theoretical connotation and clinical value. This paper summarized the clinical research literature on the differentiation and treatment of common encephalopathy based on the marrow sea theory published in recent years， analyzed the treatment method and effects from eight aspects in terms of stroke， dizziness， insomnia， headache， constraint syndrome， dementia， tremor syndrome， and atrophy syndrome， and discussed the possible mechanism based on the relevant basic research. It is believed that marrow sea depletion is the common pathogenesis of encephalopathy in TCM. Guided by the method of supplementing essence and boosting marrow， the corresponding formulas and medicinals are recommended in accordance with differentiated syndromes， which can effectively improve the symptoms of the disease， delay the progression， increase the daily life ability of the patients， and improve the quality of life. Based on the marrow sea theory， the method of supplementing essence and boosting marrow， rectifying healthy qi and dispelling pathogen can be used to highlight the advantages of TCM and provide ideas for the diagnosis and treatment of encephalopathy in TCM.

The diverse nervous system diseases （NSDs） are common complex refractory systemic diseases in clinical settings， which are manifested as trigeminal neuralgia， facial paralysis， neuromyelitis optica， multiple sclerosis， stroke， vascular dementia， encephalitis B， Parkinson's disease， epilepsy， Alzheimer's disease， amyotrophic lateral sclerosis， and diabetic peripheral neuropathy. Amid the accelerating population aging， the morbidity and prevalence of NSDs have been on the rise， posing a threat to quality of life of patients and bringing a heavy burden to society and individuals. This is also a challenge to the clinical prevention and treatment of the diseases. At the moment， NSDs are mainly treated with western medicine which is effective. However， in the long-term use and progression of the diseases， there are some potential risks such as adverse drug reactions， easy recurrence after withdrawal， drug dependence， and drug resistance. From the holistic view， traditional Chinese medicine （TCM） excels in treating diseases based on syndrome differentiation. According to the etiology， location， and pathogenesis of diseases in TCM， the overall therapy is applied， shows obvious advantages in alleviating disease symptoms， delaying disease progression， and improving the quality of life. TCM has a long history and categorizes NSDs into encephalopathy. According to clinical practice and theories， toxin is an important pathogen of NSDs in TCM. To be specific， the external toxins are insect and beast toxins， food toxin， toxin of six excesses， and epidemic toxin， and the internal toxins are phlegm toxin， dampness toxin， stasis toxin， fire toxin， and turbid toxin. Accumulation of all pathogens will lead to diseases with multiple syndromes. In the case of sudden attack of toxin， the disease is characterized by rapid onset. In the instance of fierce toxin， disease progresses rapidly. If the toxin is dependent， the disease symptoms are diverse. If the toxin is stubborn and frequently occurs， disease recurrence is common. In the case that toxin damages the collaterals， the healthy Qi is impaired. Controlling physiological function of the body， nervous system corresponds to the house of brain in TCM， which is the extraordinary organ， the house of intelligence， and the seat of mental activities that governs the whole body. In the case of toxin damaging the brain collaterals， cerebrospinal injury and orifice obstruction will occur， followed by disharmony of Qi and blood， Yin-yang imbalance， vital activity injury， disorder of primordial spirit， and dysfunction. The treatment principle should be detoxification and eliminating pathogen， and different diseases should be treated with the same method. At the moment， many doctors and scholars have focused on the prevention and treatment of NSDs based on the toxin pathogen. This paper summarizes the research on the clinical application of toxin pathogen causing disease in NSDs， including the peripheral nerve disease， demyelinating disease of the central nervous system， cerebrovascular disease， infectious disease of central nervous system， movement disorders， epilepsy， nervous system degenerative disease and nervous system complications of internal medicine disease， which is expected to provide some ideas and methods for the prevention and treatment of NSDs with TCM.

We determined molecular characteristics of Listeria monocytogenes foodborne isolates in Hangzhou and investigated the characterization of local strains.Multi-locus sequence typing(MLST) and pulsed-field gel electrophoresis(PFGE) were applied to identify molecular types of Listeria monocytogenes isolates.Results showed that a total of 133 strains of 6 serotypes were divided into 19 MLST types including a new type ST767.ST9 and ST121 were the major ST types.There were 33 and 45 PFGE patterns characterized by AscⅠ and ApaⅠ.The molecular types of Listeria monocytogenes strains were widely distributed in Hangzhou.It is indicated that the major clusters were Lineage Ⅰ and Lineage Ⅱ which will cause listeriosis.The contamination of Listeria monocytogenes in food is serious in Hangzhou and the surveillance and management should be strengthened to prevent the food borne diseases.

Diabetes is a kind of metabolic syndrome, always hap-pening in the case of insufficient secretion of insulin or insulin resistance, inducing the increase of blood glucose. While, dia-betic osteoporosis is a kind of chronic diabetic complications, which happens when insulin secretion is absolutely or relatively insufficient and then the insufficiency induces imbalance of hor-mone, calcium phosphorus metabolic disorders, thus leading to the decline of bone mineral density and change of bone micro-structure. The overnutrition, less exercise and the environment change lead to the increased incidence of diabetes. For all the diabetes, type 2 diabetes accounts for about 90%. Patients with type 2 diabetes show the increasing risk of fracture. This review summarizes the recent advances in the influence of type 2 diabe-tes on bones.

Objective To investigate the cognition and treatment rate of hormone replacement therapy (HRT)in perimenopause women.Methods A survey was conducted in 262 perimenopause women first coming to outpatients care.A predesigned structured questionnaire was used to collect information:the symptoms of perimenopa-use women,the cognition and acceptance to the treatment.Results Finally,248 women with the mean age of (50.30 ±2.10)years finished the questionnaire,the natural menopause age was (48.90 ±1.90)years.48.79% of these women understood the role of HRT in clinical application,and only 12.50% knew the side effect of HRT. Among them,35.48% thought that HRT was necessary for the duration of perimenopause.40.73% of them had the attitude to treatment with HRT.After the education of perimenopausal acknowledgement,117 patients (47.18%) accepted the treatment with HRT.Conclusion It showed that the awareness and treatment rate of HRT in perimeno-pause women was low.The health education should be strengthened to improve the level of perimenopause health care.

ObjectiveTo observe the role of Sijunzi decoction on the gut barrier protection and immunity regulation in spleen-qi deficiency type patients with persistent inflammation-immunosuppression catabolism syndrome (PICS).Methods A prospective study was conducted, and according to random number table, 46 patients with PICS accompanied by spleen-qi deficiency admitted to Department of Critical Care Medicine of Beijing Shijitan Hospital of Capital Medical University were randomly divided into two groups: control group and Sijunzi decoction group(each 23 cases). Conventional therapy was given to both groups, and the patients in Sijunzi decoction group were additionally treated with modified Sijunzi decoction 100 mL by nasal feeding, while those in the control group were treated with an equal amount of warm boiled water by nasal feeding. The course of treatment was 2 weeks in both groups. The improvement in traditional Chinese medicine(TCM) syndrome and gastrointestinal function was observed in two groups before and after treatment. At the same time, the changes of lymphocyte subsets including total T cells(CD3+ cells),helper/inducer T cells(CD3+/CD4+T cells), suppressor/cytotoxic T cells(CD3+/CD8+ T cells), CD4/CD8, total natural killer cells(NK cell,CD3-/CD16+CD56+ cells),natural killer like T cells(NK T cell,CD3+/CD16+CD56+ T cells),total B cells(CD19+ cells),regulatory T cells(Treg T cells, CD4+/CD25+ T cells),suppressor T cells(CD8+/CD28- T cells) and cytotoxic T cells(CD8+/CD28+ T cells)were analyzed.Results① There were no differences in the acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,acute gastrointestinal injury(AGI)grades and peripheral blood lymphocyte subsets between Sijunzi decoction group and control group before treatment( allP>0.05).② After 2 weeks of treatment, all the patients' clinical symptoms of spleen-qi deficiencywere improved, and there was no difference in effect between the Sijunzi decoction and control group(valid:11 cases vs. 6 cases, invalid:12 cases vs.17 cases, bothP>0.05) . In both groups, the patients' AGI condition was improved, but the improvement in treatment group was more significant than that in the control group(valid: 14 cases vs. 7 cases, P<0.05) .③ In the control group,the numbers of CD3+, CD3+/CD8+,CD8+/CD28- T cells after treatment were increased significantly〔CD3+:(62.37±7.83)% vs.(54.08±11.65)%, CD3+/CD8+:(31.52±10.55)% vs. (23.94±9.22)%, CD8+/CD28-:(24.97±10.25)% vs.(16.78±10.55)%〕 and CD19+ number was decreased obviously〔(5.78±5.33)% vs.(9.73±8.02)%〕 at the same time(allP<0.05). After treatment, in the Sijunzi decoction group, the numbers of CD3+,CD3+/CD4+, CD3+/CD8+, CD8+/CD28-, CD8+/CD28+ T cells were increased significantly compared with those before treatment〔CD3+:(74.53±7.64)% vs.(52.98±10.05)%, CD3+/CD4+:(36.27±12.08)% vs.(30.00±8.60)%, CD3+/CD8+:(37.33±12.56)% vs.(22.88±9.97)%, CD8+/CD28-:(26.89±10.80)% vs.(17.01±9.48)%, CD8+/CD28+:(12.08±5.50)% vs.(8.47±4.29)%〕, and total CD19+ number was decreased remarkably at the same time〔(4.60±4.28)% vs.(9.86±8.61)%,P<0.05〕. In the Sijunzi decoction group, after 2 weeks of treatment, the number of CD3+ T cells was increased more significantly than that in the control group〔(8.29±9.28)% vs.(5.80±5.33)%,P<0.05〕.ConclusionUsing Sijunzi decoction combined with conventional therapy can improve the clinical symptoms of patients with PICS accompanied by spleen-qi deficiency and gastrointestinal dysfunction, the mechanism is possibly via enhancing immunity by regulating the numbers of B and T lymphocytes, and maybe the cell-mediated immunity plays a more prominent role.