Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

ObjectiveTo analyze the expression of molecular marker affecting the prognosis of acute myeloid leukemia （AML） patients from bioinformatics database， thus providing an experimental basis for further exploration of a novel molecular marker for the prognosis of AML. MethodsThe prognostic data of 179 AML patients from The Cancer Genome Atlas （TCGA） database were examined for differential gene analysis and survival analysis. The bone marrow samples of 74 healthy individuals （HI） and 542 de novo AML patients in the dataset GSE13159 downloaded from the Gene Expression Omnibus （GEO） database were analyzed to detect the difference in the expression levels of differential target genes. Peripheral blood and bone marrow samples were collected from 18 de novo AML patients and 20 age- and gender-matched healthy controls， and real-time fluorescent quantitative PCR was used to validate the expression levels of the differential genes in the AML patients. ResultsBioinformatics data analysis showed that the optimal cut-off value of Homo sapiens NK2 homeobox 3 （NKX2-3） calculated by R language was 0.051. Survival analysis revealed a statistically poorer overall survival in de novo AML patients with high NKX2-3 expression than in those with low NKX2-3 expression （P = 0.0036）. NKX2-3 was highly expressed in patients with de novo AML than in HI and the difference was statistically significant （P < 0.001）. Real-time fluorescence quantitative PCR verified the expression levels of the NKX2-3 gene in AML patients and confirmed that compared with those in HI， in the de novo AML patients， NKX2-3-1 and NKX2-3-2 were highly expressed and were significantly correlated （P = 0.000， P = 0.000）. ConclusionNKX2-3 is highly expressed in de novo AML patients， and the AML patients with high NKX2-3 expression have poor overal survival. NKX2-3 may be closely related to the clinical outcome and prognosis of AML.

Objective : To screen the target of helicid in the intervention of depression based on network pharmacol- ogy and molecular docking，and to study the effect of helicid on the expression level of related targets in hippocam- pus，prefrontal cortex，striatum and habenular nucleus of chronic unpredictable mild stress ( CUMS) rats． Methods : The target of helicid was predicted by SwissTargetPrediction database ，and the depression related targets were screened by GeneCards、DisGeNet、TTD and DRUGBANK databases ; the metascape platform was used for gene en- richment analysis ，and the " helicid-depression-pathway " network was constructed ; Autodock Vina was used for molecular docking research ; qRT-PCR was used to detect the effect of helicid on the mRNA expression of HTR1A， ADORA1 and ADORA2A in rat tissues. Results : The 81 helicid targets and 1 640 depression targets were ob- tained，including 40 intersecting targets ; the key targets were mainly enriched in cAMP signal pathway，PI3K-Akt signal pathway，MAPK signal pathway and so on ; the results of molecular docking showed that the binding activity of helicid with most targets was good ; helicid up-regulated the expression levels of HTR1A ，ADORA1 and ADORA2A mRNA in hippocampus，prefrontal cortex ，striatum and habenular nucleus of CUMS rats． Conclusion Helicid may act on cAMP，PI3K-Akt，MAPK and other signal pathways to intervene depression through HTR1A， ADORA1 and ADORA2A.

Objective:To explore the features the gait of elderly persons with type 2 diabetes and peri-pheral neuropathy.Methods:Twenty patients no less than 60 years old with type 2 diabetes and peripheral neuropathy (DPN) formed a DPN group, while 20 counterparts with type 2 diabetes but without peripheral neuropathy composed the DM group, and another 20 healthy counterparts served as a control group. The three groups were tested using the Swedish Qualisys motion capture system and their walking speed, step length, step width, stride frequency and stride length, bipedal foot support phase time, single foot support phase time, peak plantar pressure, and regional-holding time were collected and compared.Results:The average walking speed, stride length and stepping frequency of the DPN group were all significantly lower than the other 2 groups′ averages. Their bipedal support phase was significantly longer, but their single foot support phase time was significantly shorter. And in the DPN group the average first and second peak plantar pressures and the second peak pressure time were significantly greater than the other groups′ averages.Conclusions:Elderly patients with type 2 diabetes and peripheral neuropathy have significant gait abnormalities, decreased walking stability, as well as increased plantar pressure and plantar compression time.

Objective:To investigate the clinical value of single embryo transfer for the patients with gonadotropin-releasing hormone (GnRH) antagonist protocol.Methods:The clinical data of the patients underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in Reproductive Medicine Center, the 901th Hospital of the Joint Logistics Support Force of PLA from January 2017 to March 2021 were retrospectively analyzed in this cohort study. According to the days of embryo development and No. of embryos, patients were divided into day 3 (D3) single top-quality cleavage-stage embryo transfer group (single top-quality embryo group), D3 double top-quality cleavage-stage embryo transfer group (double top-quality embryos group), and single blastocyst transfer group. In fresh cycles, there were 301 patients in single top-quality embryo group, 253 patients in double top-quality embryos group and 127 patients in single blastocyst group in frozen-thawed embryo transfer (FET) cycles,there were 84 patients in single top-quality embryo group, 136 patients in double top-quality embryos group and 396 patients in single blastocyst group in first FET cycles after all embryos frozen,there were 69 patients in single top-quality group and 161 patients in single blastocyst group. The rates of clinical pregnancy, implantation, multiple pregnancy, early abortion and ongoing pregnancy in the fresh and FET cycles were compared among single top-quality embryo group, double top-quality embryos group and single blastocyst group. Also, the rates of clinical pregnancy, implantation, multiple pregnancy, early abortion and ongoing pregnancy of single top-quality embryo transfer and single blastocyst transfer were compared between the fresh cycle and the first FET cycle. One-way ANOVA and chi-square test were used in this study. Results:There were no significant difference in duration of infertility, body mass index (BMI), the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone (AMH), gonadotropin (Gn) and the numbers of oocytes retrieved among all the groups (all P>0.05). There were no significant differences in the rates of clinical pregnancy, implantation, multiple pregnancy, early abortion and ongoing pregnancy between single top-quality embryo group and single blastocyst group (all P>0.05) in fresh cycle, while the clinical pregnancy rate [46.18% (139/301)], the ongoing pregnancy rate [40.86% (123/301)] and the multiple pregnancy rate [0% (0/139)] in single top-quality embryo group were significantly lower than those in double top-quality embryos group [58.89% (149/253), P<0.001; 52.17% (132/253), P<0.001; 30.20% (45/149), P<0.001], with the similar implantation rate between the two groups ( P>0.016 7). The rates of clinical pregnancy, implantation and ongoing pregnancy were comparable between single top-quality embryo group and double top-quality embryos group in FET cycle ( P>0.016 7), while which were all significantly lower than those in single blastocyst group [62.88% (249/396), P<0.001; 63.89% (253/396), P<0.001; 55.30% (219/396), P<0.001]. The multiple pregnancy rate of double top-quality embryos group [20.37% (11/54)] was significantly higher than that of single top-quality embryo group [0% (0/27), P=0.013] in FET cycle. The ongoing pregnancy rate of the single top-quality embryo transfer in first FET cycle [27.54% (19/69)] was significantly lower than that in fresh cycle [40.86% (123/301), P=0.040], while the clinical pregnancy rate [63.35% (102/161)] and the implantation rate [63.98% (103/161)] of single blastocyst transfer in first FET cycle were significantly higher than those in fresh cycle [50.39% (64/127), P=0.027; 51.97% (66/127), P=0.040]. Conclusion:The clinical outcomes of D3 single top-quality cleavage-stage embryo transfer were similar to D5 single blastocyst transfer in fresh cycle, while the clinical outcomes of single blastocyst transfer in FET cycle were better compared with fresh cycle for the patients with GnRH antagonist protocol. Single embryo transfer can significantly reduce the multiple pregnancy rate of IVF/ICSI .

Objective:To investigate the clinical value of single embryo transfer for the patients with gonadotropin-releasing hormone (GnRH) antagonist protocol.Methods:The clinical data of the patients underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in Reproductive Medicine Center, the 901th Hospital of the Joint Logistics Support Force of PLA from January 2017 to March 2021 were retrospectively analyzed in this cohort study. According to the days of embryo development and No. of embryos, patients were divided into day 3 (D3) single top-quality cleavage-stage embryo transfer group (single top-quality embryo group), D3 double top-quality cleavage-stage embryo transfer group (double top-quality embryos group), and single blastocyst transfer group. In fresh cycles, there were 301 patients in single top-quality embryo group, 253 patients in double top-quality embryos group and 127 patients in single blastocyst group in frozen-thawed embryo transfer (FET) cycles,there were 84 patients in single top-quality embryo group, 136 patients in double top-quality embryos group and 396 patients in single blastocyst group in first FET cycles after all embryos frozen,there were 69 patients in single top-quality group and 161 patients in single blastocyst group. The rates of clinical pregnancy, implantation, multiple pregnancy, early abortion and ongoing pregnancy in the fresh and FET cycles were compared among single top-quality embryo group, double top-quality embryos group and single blastocyst group. Also, the rates of clinical pregnancy, implantation, multiple pregnancy, early abortion and ongoing pregnancy of single top-quality embryo transfer and single blastocyst transfer were compared between the fresh cycle and the first FET cycle. One-way ANOVA and chi-square test were used in this study. Results:There were no significant difference in duration of infertility, body mass index (BMI), the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone (AMH), gonadotropin (Gn) and the numbers of oocytes retrieved among all the groups (all P>0.05). There were no significant differences in the rates of clinical pregnancy, implantation, multiple pregnancy, early abortion and ongoing pregnancy between single top-quality embryo group and single blastocyst group (all P>0.05) in fresh cycle, while the clinical pregnancy rate [46.18% (139/301)], the ongoing pregnancy rate [40.86% (123/301)] and the multiple pregnancy rate [0% (0/139)] in single top-quality embryo group were significantly lower than those in double top-quality embryos group [58.89% (149/253), P<0.001; 52.17% (132/253), P<0.001; 30.20% (45/149), P<0.001], with the similar implantation rate between the two groups ( P>0.016 7). The rates of clinical pregnancy, implantation and ongoing pregnancy were comparable between single top-quality embryo group and double top-quality embryos group in FET cycle ( P>0.016 7), while which were all significantly lower than those in single blastocyst group [62.88% (249/396), P<0.001; 63.89% (253/396), P<0.001; 55.30% (219/396), P<0.001]. The multiple pregnancy rate of double top-quality embryos group [20.37% (11/54)] was significantly higher than that of single top-quality embryo group [0% (0/27), P=0.013] in FET cycle. The ongoing pregnancy rate of the single top-quality embryo transfer in first FET cycle [27.54% (19/69)] was significantly lower than that in fresh cycle [40.86% (123/301), P=0.040], while the clinical pregnancy rate [63.35% (102/161)] and the implantation rate [63.98% (103/161)] of single blastocyst transfer in first FET cycle were significantly higher than those in fresh cycle [50.39% (64/127), P=0.027; 51.97% (66/127), P=0.040]. Conclusion:The clinical outcomes of D3 single top-quality cleavage-stage embryo transfer were similar to D5 single blastocyst transfer in fresh cycle, while the clinical outcomes of single blastocyst transfer in FET cycle were better compared with fresh cycle for the patients with GnRH antagonist protocol. Single embryo transfer can significantly reduce the multiple pregnancy rate of IVF/ICSI .

Alanyl-glutamine dipeptide is an important component in parenteral nutrition, which can be decomposed into alanine and L-glutamine in vivo. It plays multiple functions including maintaining intestinal barrier, improving immunity, promoting protein synthesis, and regulating the production and release of inflammatory mediators. Substantial clinical evidences have demonstrated its favorable effectiveness and safety. Rational application of alanyl-glutamine dipeptide can reduce postoperative complications, shorten hospital stay and save medical costs. There are still controversies at home and abroad on the applicable population and dosage of alanyl-glutamine dipeptide. Chinese Society of Parenteral and Enteral Nutrition organized China's experts of related disciplines to compile international standards in accordance with the latest guidelines and consensus, so as to achieve the goal of standardized application and patient benefits.

Objective:To investigate the effects of blastulation and transferred blastocyst derived from the 4-5-cell grade I to III (4/I-5/III) embryos on day 3 on clinical outcomes of in vitro fertilization and embryo transfer (IVF-ET). Methods:A total of 884 IVF cycles with blastocyst culture in the 901st Hospital of the Joint Logistics Support Force of PLA from January 2016 to February 2019 were retrospectively analyzed. The blastocyst formation status was compared among the 4/I-5/III embryos. Blastocyst derived from 4/I-5/III embryos in transfer cycle was served as group A ( n=164), blastocyst derived from good-quality cleavage stage embryos (7/I-10/II) in transfer cycle was served as group B ( n=247) according to quality of cleavage stage embryos on day 3. The clinical outcomes were compared between the two groups. The effects of different blastomere number and grade on clinical pregnancy rate and spontaneous abortion rate were evaluated among the 4/I-5/III embryos. Results:Good-quality blastulation rate for 4/I, 4/II, 4/III, 5/I, 5/II and 5/III were 5.6%, 1.8%, 0.6%, 8.3%, 8.4% and 1.6%, respectively. The differences reached statistical significances ( P<0.05). There were no significant differences in number of oocytes retrieved, number of mature oocytes, fertilization rate, cleavage rate, number of transferred embryos, percentage of good-quality blastocyst transfer cycles, clinical pregnancy rate, spontaneous abortion rate, implantation rate and ongoing pregnancy rate between group A and group B ( P>0.05), group A had higher number of embryo transfer cycles ( P=0.034) and lower good-quality embryo rate on day 3 ( P<0.001). There were no significant differences in clinical pregnancy rate and spontaneous abortion rate between transferred blastocyst derived from the 4-cell and 5-cell embryo (51.6% vs. 50.0%；15.2% vs. 26.8%, respectively). There were no significant differences in clinical pregnancy rate and spontaneous abortion rate between transferred blastocyst derived from grade I+II and grade III (4/I-5/III) (53.6% vs. 41.2%； 22.4% vs. 21.4%, respectively). Conclusion:Blastocyst derived from 4/I-5/III embryos and good cleavage stage embryos both are similar clinical outcomes in blastocyst transfer cycles, there are no effects of blastomere number and grade on clinical pregnancy rate and abortion rate in blastocyst transfer cycles, but blastulation rate derived from 5-cell embryo was significantly higher than that of 4-cell embryo.