Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

This paper aimed to study phenylpropanoids of Tripterygium hypoglaucum. Twenty-four compounds were isolated from the 70% EtOH extracts of T. hypoglaucum by silica gel column chromatography, reversed phase column chromatography, gel column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography. Compounds 1-3 were three new phenylpropionds. Their structures were identified by ultraviolet spectrum, infrared spectroscopy, high resolution electrospray ionization mass spectrometry, and nuclear magnetic resonance data as: threo-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanedol (1), erythro-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (2), erythro-3-(4-hydroxy-3,5-dimethoxyphenyl)-3-ethoxypropane-1,2-propanediol (3). Compounds 4-6, 9, 14, 15, 18, 19, and 21-24 were obtained from Tripterygium genus for the first time. The cytotoxicity assay of cancer cells suggested that compound 20 displayed cytotoxicity on the breast cancer 4T1 cells whose 50% inhibitory concentration was 125.60 μmol·L^-1.

Objective To investigate the efficacy of Jingangteng Capsules combined with Guizhi Fuling Capsules(GFC)for the treatment of patients with chronic pelvic inflammation of damp-heat and stasis obstruction type and to observe their effects on serum granulocyte-macrophage colony-stimulating factor(GM-CSF)and matrix metalloproteinase 2(MMP-2)levels.Methods Ninety patients with chronic pelvic inflammation of damp-heat and stasis obstruction type were randomly divided into the combined group and the GFC group,with 45 patients in each group.Patients in the GFC group were treated with Guizhi Fuling Capsules,while patients in the combined group were given Jingangteng Capsules together with GFC.The treatment period lasted for 2 weeks and then one-month follow-up was conducted.The changes of traditional Chinese medicine(TCM)scores,serum GM-CSF and MMP-2 levels in the two groups were observed before and after treatment.And the clinical efficacy,time for the relief of symptoms,recurrence of disease and occurrence of adverse reactions in the two groups were compared.Results(1)After 2 weeks of treatment,the total effective rate of the combined group was 93.33%(42/45),and that of the GFC group was 66.67%(30/45).The intergroup comparison showed that the therapeutic effect of the combined group was significantly superior to that of the GFC group when comparing the two groups(P＜0.01).(2)After treatment,the scores of TCM symptoms of lower abdominal pain,lumbosacral pain,leukorrhagia,profuse menstruation,dysmenorrhea,and fatigue in both groups were significantly lower than those before treatment(P＜0.05),and the reduction of TCM syndrome scores in the combined group was significantly superior to that in the GFC group(P＜0.05).(3)The time for leucorrhea recovering normal and the time for the relief of lower abdominal distension and abdominal pain in the combined group were significantly shorter than those in the GFC group after treatment(P＜0.01).(4)After treatment,the serum serological indicators of GM-CSF and MMP-2 levels in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the reduction of serum GM-CSF and MMP-2 levels in the combined group was significantly superior to that in the GFC group(P＜0.05 or P＜0.01).(5)The recurrence rate and the incidence rate of adverse reactions in the combined group were 11.11%(5/45)and 13.33%(6/45),respectively,and were significantly lower than those in the GFC group[all being 35.56%(16/45)],the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Jingangteng Capsules combined with Guizhi Fuling Capsules can significantly enhance the clinical efficacy of the patients with chronic pelvic inflammatory of damp-heat and stasis obstruction type,effectively shorten the time for the relief of symptoms,and decrease the serum GM-CSF and MMP-2 levels.

Objective To investigate the association between body mass index(BMI),sex hormone and single nucleotide polymorphisms(SNPs)of follicle-stimulating hormone receptor(FSHR)gene rs2268361 and rs2349415 and its correlation with the risk of polycystic ovary syndrome(PCOS).Methods Peripheral blood was collected from 213 PCOS patients and 207 healthy controls,attending the Department of Reproductive Medicine at the First Hospital of Shanxi Medical University,and 32 follicular fluids were randomly collected from each of the PCOS and control groups from March to August 2021.Calculation of BMI of the PCOS and control groups;The levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),testosterone(T),progesterone(P)and prolactin(PRL)in peripheral blood of the two groups were detected by immunochemiluminescence method.Polymerase chain reaction(PCR)and high-resolution melting curve(HRM)were used to analyze the polymorphisms of rs2268361 and rs2349415 in FSHR of the two groups.Quantitative real-time PCR was used to detect the expression of FSHR gene mRNA in peripheral blood and ovarian granulosa cells.Results There was a strong positive correlation between LH and LH/FSH(r=0.88,P<0.05);The levels of BMI,E2,LH,LH/FSH and T in PCOS group were significantly higher than those in control group(P<0.05);FSH level was significantly lower than that of control group(P<0.001).HRM analysis showed the frequencies of CC,CT and TT genotypes at rs2349415 were 55.9%,34.3%and 9.8%in PCOS group and 68.6%,23.2%and 8.2%in control group,respectively.The frequencies of C and T alleles were 73.0%and 27.0%in PCOS group and 80.2%and 19.8%in control group,respectively.There were significant differences in genotype frequencies and allele frequencies between the two groups(P<0.05);The expression level of FSHR mRNA was higher in ovarian granulosa cells in PCOS group than in control group(P=0.004),the expression level of FSHR mRNA in rs2349415 TT genotype was higher than that in CC(P=0.002)and CT(P=0.035)genotype.Conclusion High levels of BMI, LH, E2 and T allele of rs2349415 increased the risk of PCOS.

Objective To investigate the effects of Shugan Bushen Decoction combined with laparoscopic surgery on ovarian volume,serum homeobox gene A10(HOXA10)expression and pregnancy rate in patients with refractory polycystic ovary syndrome(PCOS).Methods A total of 80 patients with refractory PCOS of liver stagnation and kidney deficiency type were randomly divided into an observation group and a control group,with 40 cases in each group.The control group was given conventional laparoscopic surgery and conventional medicine treatment.The observation group was treated with Shugan Bushen Decoction on the basis of treatment for the control group.One menstrual cycle constituted one course of treatment,and 3 continuous courses of treatment were given.The changes of traditional Chinese medicine(TCM)syndrome scores,ovarian volume,follicular diameter,serum HOXA10 expression and levels of sex hormones of luteinizing hormone(LH),estradiol(E2),progesterone(P),follicle stimulating hormone(FSH)and testosterone in the two groups before and after treatment were observed.Moreover,the pregnancy outcomes of the two groups during the follow-up for half a year were monitored.Results(1)After treatment,the ovarian volume in the two groups was decreased to different degrees(P＜0.05),and the follicular diameter was increased to different degrees(P＜0.05).The intergroup comparison showed that the decrease of ovarian volume and the increase of follicular diameter in the observation group were significantly superior to those in the control group(P＜0.01).(2)After treatment,the levels of LH,FSH and testosterone in the two groups were significantly lower than those before treatment(P＜0.05),and the levels of HOXA10,E2 and P were significantly higher than those before treatment(P＜0.05).The decrease of LH,FSH and testosterone levels and the increase of HOXA10,E2 and P levels in the observation group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the overall TCM syndrome scores and the scores of the syndrome manifestations of abnormal menstrual volume,abnormal menstrual cycle,soreness and weakness of waist and knees,darkish red tongue,deep and unsmooth pulse in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of overall TCM syndrome scores and the scores of each of the syndrome manifestations in the observation group was significantly superior to that in the control group,the differences being statistically significant(P＜0.01).(4)The pregnancy rate of the observation group was 55.00%(22/40),which was significantly higher than that of 32.50%(13/40)in the control group,and the difference was statistically significant(P＜0.05).Conclusion For the treatment of refractory PCOS of liver depression and kidney deficiency type,Shugan Bushen Decoction combined with laparoscopic surgery can effectively improve the ovarian function of the patients,promote the recovery of sex hormone levels,increase the expression level of HOXA10,improve the endometrial receptivity,and enhance the pregnancy rate of the patients.

For the treatment of atrial fibrillation,Professor WU Wei innovatively put forward the theory of heart-blood-vessels trinity and the theory of stasis-toxin causing palpitation.It is believed that atrial fibrillation is caused by stasis and toxin,and affects the heart,blood and vessels.The core pathogenesis of atrial fibrillation is due to qi stagnation,blood stasis and toxin.The treatment for atrial fibrillation should be closely based on the pathogenesis,the therapeutic principles of treating from the perspective of stasis and together by removing toxin gradually is advocated.And the therapy of regulating qi,activating blood and removing stasis is also the way to remove toxin.The medication is based on the modified Taoren Honghua Decoction,which is mainly composed of Persicae Semen,Carthami Flos,Chuanxiong Rhizoma,Corydalis Rhizoma,Rehmanniae Radix,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Jujubae Fructus,Puerariae Lobatae Radix,Nardostachyos Radix et Rhizoma,Ostreae Concha,Poria,and Polygonati Odorati Rhizoma.According to the characteristics of Lingnan climate and atrial fibrillation mostly being easy to affect the emotions,the pungent drugs in the prescription are usually removed,and the specific herbal pair of Puerariae Lobatae Radix-Nardostachyos Radix et Rhizoma is added to remove toxin according to the differentiation of disease.Moreover,for the treatment of atrial fibrillation,Professor WU Wei also adopts traditional Chinese medicine(TCM)external treatment such as foot bath,acupuncture and moxibustion,and physical-breathing exercise as well as health-care methods for comprehensive regulation,relieving the toxin and restoring the original qi.During the treatment atrial fibrillation,Professor WU Wei follows the principle of precise intervention and comprehensive regulation with Chinese medicine,so as to achieve the purpose of eliminating symptoms,restoring sinus rhythm and improving physical constitution.The thoughts of Professor WU Wei for the syndrome differentiation and treatment of atrial fibrillation will provide reference for the treatment of atrial fibrillation with TCM.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.