Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

L-valine is an important branched-chain amino acid widely used in the food, pharmaceutical, and feed industries. Microbial fermentation has become the primary production method for L-valine. However, current industrial production still faces issues such as inefficient carbon flux utilization, imbalance in cofactor supply and demand, and suboptimal fermentation processes, which limit the efficient synthesis of L-valine. To further enhance the production performance of L-valine, In this study, metabolic engineering was conducted for a previously constructed Escherichia coli strain with a high yield of L-valine to optimize carbon flux distribution and balance cofactor consumption. Dual-phase oxygen-controlled fermentation was carried out to enhance L-valine production. Firstly, to address the pyruvate loss, we knocked out multiple competing pathway genes (ldhA, poxB, pflB, frdA, and pta), which resulted in a 48% increase in flask yield of the constructed strain VL-04. Next, we optimized the cofactor supply and demand balance by replacing ilvE with bcd (NADH-preferential) from Bacillus subtilis to construct the strain VL-06, which achieved a flask yield of 22.80 g/L, a further improvement of 25.8%. Subsequently, the fermentation conditions of VL-06 were optimized in a 5 L bioreactor with dual-phase oxygen-controlled fermentation. After optimization, the L-valine production reached 86.44 g/L in 26 h, with a glucose-to-acid conversion rate of 44.08% and a production intensity of 3.32 g/(L·h). This study not only shortens the time for L-valine production but also improves the economic efficiency, providing insights for similar fermentation processes employing dual-phase oxygen control.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Valine/biosynthesis* ; Fermentation ; Bacillus subtilis/genetics*

Objective::To use fetal heart quantification ( fetal HQ) technology to compare the coarctation of the aorta (CoA) and normal fetal heart structure and systolic function and to assess whether there are abnormalities in the fetal heart structure and systolic function associated with CoA. Methods::This prospective cohort study was conducted from May 2020 to December 2022 and involved 18-40-week-old singleton pregnancies and 30 fetuses diagnosed with CoA using fetal echocardiography at the General Hospital of Ningxia Medical University and Peking University First Hospital Ningxia Women’s and Children’s Hospital, China. The control group contained 60 normal fetuses. The following parameters were recorded and analyzed statistically: four-chamber view (4CV) end-diastolic long diameter, 4CV epicardial-contralateral epicardial transverse maximum diameter, 4CV global sphericity index (GSI), left ventricular (LV) and right ventricular (RV) 24-segment end-diastolic diameter (EDD), 24-segment sphericity index (SI), LV-fractional area change (LV-FAC), LV-longitudinal strain (LV-LS), RV-fractional area change (RV-FAC), RV-longitudinal strain (RV-LS), and LV and RV 24-segment transverse fractional shortening (FS). Measurement data were compared between the two groups using an independent sample t test, with P < 0.05 indicating statistically significant differences. Moreover, the correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS was assessed. Results::Within and between observer comparisons of the parameters associated with major cardiac function revealed an intragroup correlation coefficient of >0.9, indicating high consistency, and a coefficient of variable of <1 %, indicating low variability. Correlation analysis revealed no obvious correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS. A comparison of the four-chamber morphological structural parameters of the hearts in the two groups revealed that when compared with the control group, the 4CV end-diastolic long diameter was shortened in fetuses in the CoA group and the epicardial-contralateral epicardial transverse maximum diameter was wider, while the GSI was lower ( P < 0.05). A comparison of the LV and RV morphological structure parameters between the two groups revealed that when compared with the control group, the LV’s 24-segment EDD was smaller in the CoA group, the RV’s 24-segment EDD was greater in the control group, the SI of the LV’s segments 16-24 was greater than in the control group, and the SI of the RV’s segments 7-24 was less than in the control group (all P < 0.05). When compared with fetuses in the control group, the LV’s segments 16-24 were greater in the CoA group, whereas the RV’s segment 6-24 was smaller ( P < 0.05). When compared with the control group, LV-FAC, RV-FAC, and LS were lower in the CoA group ( P < 0.05). The FS of the LV segments 1-24 and the FS of the RV segments 1-16 were smaller in the CoA group than in the normal group ( P < 0.05). Conclusion::Fetal HQ, a new simple technique that offers rapid analysis and high repeatability, can quantitatively evaluate structural and systolic function changes in fetuses with CoA.

Objective::To use fetal heart quantification ( fetal HQ) technology to compare the coarctation of the aorta (CoA) and normal fetal heart structure and systolic function and to assess whether there are abnormalities in the fetal heart structure and systolic function associated with CoA. Methods::This prospective cohort study was conducted from May 2020 to December 2022 and involved 18-40-week-old singleton pregnancies and 30 fetuses diagnosed with CoA using fetal echocardiography at the General Hospital of Ningxia Medical University and Peking University First Hospital Ningxia Women’s and Children’s Hospital, China. The control group contained 60 normal fetuses. The following parameters were recorded and analyzed statistically: four-chamber view (4CV) end-diastolic long diameter, 4CV epicardial-contralateral epicardial transverse maximum diameter, 4CV global sphericity index (GSI), left ventricular (LV) and right ventricular (RV) 24-segment end-diastolic diameter (EDD), 24-segment sphericity index (SI), LV-fractional area change (LV-FAC), LV-longitudinal strain (LV-LS), RV-fractional area change (RV-FAC), RV-longitudinal strain (RV-LS), and LV and RV 24-segment transverse fractional shortening (FS). Measurement data were compared between the two groups using an independent sample t test, with P < 0.05 indicating statistically significant differences. Moreover, the correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS was assessed. Results::Within and between observer comparisons of the parameters associated with major cardiac function revealed an intragroup correlation coefficient of >0.9, indicating high consistency, and a coefficient of variable of <1 %, indicating low variability. Correlation analysis revealed no obvious correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS. A comparison of the four-chamber morphological structural parameters of the hearts in the two groups revealed that when compared with the control group, the 4CV end-diastolic long diameter was shortened in fetuses in the CoA group and the epicardial-contralateral epicardial transverse maximum diameter was wider, while the GSI was lower ( P < 0.05). A comparison of the LV and RV morphological structure parameters between the two groups revealed that when compared with the control group, the LV’s 24-segment EDD was smaller in the CoA group, the RV’s 24-segment EDD was greater in the control group, the SI of the LV’s segments 16-24 was greater than in the control group, and the SI of the RV’s segments 7-24 was less than in the control group (all P < 0.05). When compared with fetuses in the control group, the LV’s segments 16-24 were greater in the CoA group, whereas the RV’s segment 6-24 was smaller ( P < 0.05). When compared with the control group, LV-FAC, RV-FAC, and LS were lower in the CoA group ( P < 0.05). The FS of the LV segments 1-24 and the FS of the RV segments 1-16 were smaller in the CoA group than in the normal group ( P < 0.05). Conclusion::Fetal HQ, a new simple technique that offers rapid analysis and high repeatability, can quantitatively evaluate structural and systolic function changes in fetuses with CoA.

In recent years, incentive spirometry has been gradually applied to prevent and reduce postoperative pulmonary complications due to its advantages of simple operation, low price and visual feedback for patients. In this paper, the use device and method of incentive spirometry, and the prevent and application status of incentive spirometry in pulmonary complications after chest, abdomen and heart surgery are reviewed, with a view to providing reference for the promotion and application of incentive spirometry in China.

Cathartic colon （CC） is a common and refractory digestive system disease， with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore， establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine （TCM） is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals， drugs and their dosage forms， doses， administration methods， and modeling period of CC varied in different studies， and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing， which， however， may cause water electrolyte disorders， decreased immunity， and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose， while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools， and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles， approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition， the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes： liver depression and spleen deficiency， both Qi and Yin deficiency， Qi stagnation and blood stasis， and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM， so as to facilitate the research on CC mechanism and drug development.

Objective:To review the mechanism of the effects of aviation flight on pregnant women and to summarize the diseases and suggestions that obstetricians should pay attention to for the pregnant women with flight plan.Literature resource and selection:Relevant literature on the subject of impact of aviation flight on pregnant women published in China and abroad.Literature quotation:Thirty-four references were cited.Literature synthesis:Aviation flight exposes the people on board into decreased oxygen partial pressure, humidity, air pressure and increased amount of radiation environment. And those would bring some physiological changes to the pregnant women in flight. However, these changes have little impact on the pregnant women who occasionally take airplane and have no obstetrical or other medical complications besides some discomfort. For the passengers or crew members, who frequently take airplanes, aviation flight can increase the incidence of spontaneous abortions or missed abortions. The long duration flight also increases the risk of deep venous thrombosis in pregnant women. It is recommended that pregnant women would go to the hospital to check whether they are suffering from related diseases that are not suitable for flight before they make flight plan. For the pregnant women who plan to fly for more than 4 h, it is recommended to use gradient elastic compression stockings to prevent venous thrombosis.Conclusions:Although the flight brings certain influences on pregnant women, but the understandings of influential mechanism and risk factors, as well as the proactive prevention would help them to overcome the influences and to relieve the tension in flight.

5-aminolevulinic acid (5-ALA) plays an important role in the fields of medicine and agriculture. 5-ALA can be produced by engineered Escherichia coli and Corynebacterium glutamicum. We systematically engineered the C4 metabolic pathway of C. glutamicum to further improve its ability to produce 5-ALA. Firstly, the hemA gene encoding 5-ALA synthase (ALAS) from Rhodobacter capsulatus and Rhodopseudomonas palustris were heterologously expressed in C. glutamicum, respectively. The RphemA gene of R. palustris which showed relatively high enzyme activity was selected. Screening of the optimal ribosome binding site sequence RBS5 significantly increased the activity of RphemA. The ALAS activity of the recombinant strain reached (221.87±3.10) U/mg and 5-ALA production increased by 14.3%. Subsequently, knocking out genes encoding α-ketoglutarate dehydrogenase inhibitor protein (odhI) and succinate dehydrogenase (sdhA) increased the flux of succinyl CoA towards the production of 5-ALA. Moreover, inhibiting the expression of hemB by means of sRNA reduced the degradation of 5-ALA, while overexpressing the cysteine/O-acetylserine transporter eamA increased the output efficiency of intracellular 5-ALA. Shake flask fermentation using the engineered strain C. glutamicum 13032/∆odhI/∆sdhA-sRNAhemB- RBS5RphemA-eamA resulted in a yield of 11.90 g/L, which was 57% higher than that of the original strain. Fed-batch fermentation using the engineered strain in a 5 L fermenter produced 25.05 g/L of 5-ALA within 48 h, which is the highest reported-to-date yield of 5-ALA from glucose.
Aminolevulinic Acid/metabolism* ; Corynebacterium glutamicum/metabolism* ; Fermentation ; Metabolic Engineering ; Rhodobacter capsulatus/enzymology* ; Rhodopseudomonas/enzymology*

Objective:To review the mechanism of the effects of aviation flight on pregnant women and to summarize the diseases and suggestions that obstetricians should pay attention to for the pregnant women with flight plan.Literature resource and selection:Relevant literature on the subject of impact of aviation flight on pregnant women published in China and abroad.Literature quotation:Thirty-four references were cited.Literature synthesis:Aviation flight exposes the people on board into decreased oxygen partial pressure, humidity, air pressure and increased amount of radiation environment. And those would bring some physiological changes to the pregnant women in flight. However, these changes have little impact on the pregnant women who occasionally take airplane and have no obstetrical or other medical complications besides some discomfort. For the passengers or crew members, who frequently take airplanes, aviation flight can increase the incidence of spontaneous abortions or missed abortions. The long duration flight also increases the risk of deep venous thrombosis in pregnant women. It is recommended that pregnant women would go to the hospital to check whether they are suffering from related diseases that are not suitable for flight before they make flight plan. For the pregnant women who plan to fly for more than 4 h, it is recommended to use gradient elastic compression stockings to prevent venous thrombosis.Conclusions:Although the flight brings certain influences on pregnant women, but the understandings of influential mechanism and risk factors, as well as the proactive prevention would help them to overcome the influences and to relieve the tension in flight.

This study was aimed to analyze and summarize the intervention rule on traditional Chinese medicine (TCM) external treatment of primary dysmenorrhea,in order to provide theoretical evidences for clinical treatment.Articles on TCM external treatment of primary dysmenorrhea published both at home and abroad were search in the CNKI from January Ft,2014 to January Ft,2017.After standard screening,the frequency analysis,cluster analysis and association analysis were conducted.The results showed that acupuncture was the mostly used TCM external treatment of primary dysmenorrhea,which was far more than other types of TCM external treatments.Theoretical studies on single usie of acupuncture or single use of moxibustion were far more than clinical trials.The acupoint used with the highest frequency in primary dysmenorrhea treatment was SP-6 Sanyinjiao.RN-4 Guanyuan was the second and SP-8 Diji was the third.A total of 22 classic acupoint combinations were identified.It was concluded that the main external intervention method of primary dysmenorrhea was acupuncture with SP-6,RN-4 and SP-8 as its main acupoints.There are a total of 22 classic acupoint combinations