The discovery of hemoglobin variants with low oxygen affinity,diagnostic methods,prognosis of carriers,and developments in analyzing hemoglobin oxygen-carrying and-releasing abilities are reviewed in this article in order to draw the attention of related clinical departments and to provide references for optimizing the process of diagnosis and treatment.Hemoglobin variants with low oxygen affinity originate from gene mutations encoding hemoglobin and autosomal dominant inheritance.The diagnosis should be combined with clinical manifestations and family history and differentiated from methemoglobinemia.A decrease in pulse oxygen saturation(SpO2)is often the first abnormality observed in asymptomatic carriers of hemoglobin variants with low oxygen affinity.Laboratory examinations include arterial blood gas analysis,hemoglobin oxygen affinity testing,protein analysis and gene sequencing.Most carriers do not require specific treatment and have a good prognosis,who should avoid acute hypoxic injuries induced by strenuous exercise,emotional stress,or high temperature.Moreover,health practitioners should pay attention to their responses to anesthetics,agents that induce oxidative stress,drugs that increase hemoglobin oxygen affinity,and prostacyclins.Hemoglobin oxygen-carrying and-releasing analysis is a promising tool to identify carriers of hemoglobin variants with low oxygen affinity because it does not involve unnecessary or invasive examinations and is of significant values for clinical diagnosis and treatment.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.

Objective:To explore the application effect of online-offline mixed teaching mode in the teaching of histology and embryology.Methods:Two classes of students majoring in psychiatry from Batch 2020 were randomized into experimental group ( n = 100), and two classes of students majoring in general practice in 2020 grade were randomized into the control group ( n = 99). The online-offline mixed teaching mode was used in the experimental group, while a traditional teaching mode was used in the control group. The online test scores, final scores and questionnaire satisfaction of the two groups of students were evaluated on the teaching effect. All data were statistically processed by SPSS 19.0, and the comparison between groups was performed by t test. Results:The online test scores of the experimental group [(8.55±1.18) vs. (6.33±0.91)] and final scores [(85.56±3.32) vs. (72.24±2.71)] were significantly higher than those of the control group ( P < 0.05). Compared with the control group, the experimental group's satisfaction scores of the online-offline mixed teaching mode were significantly higher in students' learning interest, learning autonomy, time management ability, teamwork, interactive communication, knowledge understanding and memory ability ( P < 0.05). Conclusion:The online-offline mixed teaching mode can improve the histology and embryology teaching effect and promote the students' interest in learning and autonomous learning ability.

Objective:To evaluate the clinical efficacy of neck pricking combined with oral pricking in the treatment of dysphagia after stroke.Methods:Seventy-four patients with post-stroke dysphagia who met the inclusion criteria were randomly divided into the treatment group (acupuncture + rehabilitation training group) and the control group (rehabilitation training group) according to random number table method, 37 cases for each group. Both groups of patients were given conventional drug therapy and rehabilitation of Chinese and Western medicine. On this basis, the control group used swallowing rehabilitation training. The treatment group used acupuncture combined with neck pricking and oral pricking based on swallowing rehabilitation training. Both groups were treated for 3 weeks. Before and after the treatment, three different traits of sputum (liquid, mushy and paste) videofluoroscopic swallowing study (VFSS) were observed for each patient, and the swallowing conditions were observed. The primary outcome measures were the oral swallowing scale score, the pharyngeal swallowing scale score, the Rosenbek infiltration/aspiration scale score, and the standard swallowing function rating scale (SSA). The improvement in swallowing function and aspiration was compared between the two groups.Results:After treatment, the SSA score of the treatment group (25.05 ± 5.27 vs. 28.66 ± 5.33, t=2.884) was lower than that of the control group ( P<0.05). Compared with the same group before treatment, treatment group and control group of oral stage VFSS liquid ( t=5.199, 5.413), mushy ( t=4.761, 4.824) and pasty ( t=5.295, 4.428) scores, throat stage liquid ( t=4.986, 3.919), mushy ( t=4.789, 4.170) and pasty ( t=4.136, 3.673) scores were increased ( P<0.01), but there was no statistically significant difference between the groups ( P>0.05). After treatment, Rosenbek's leakage-aspiration degree classification was significantly reduced ( Z values were 4.224, 2.956, all Ps<0.01), but there was no statistically significant difference between the groups ( P>0.05). The total effective rate was 89.2% (33/37) in the treatment group and 74.3% (26/35) in the control group. There was no statistically significant difference between the two groups ( Z=1.125, P=0.261). Conclusions:Neck pricking combined with oral pricking and rehabilitation training for stroke dysphagia is better than simple rehabilitation training, and could significantly improve swallowing-feeding function, which could be promoted in clinical rehabilitation.

Objective: To investigate the diagnosis and treatment for enterocutaneous fistula (ECF) in China, and to explore the prognostic factors of ECF. Methods: A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of ECF patients from 54 medical centers in 22 provinces/municipalities from January 1, 2018 to December 31, 2018. The clinical data included patient gender, age, length of hospital stay, intensive care unit (ICU) admission, underlying diseases, primary diseases, direct causes of ECF, location and type of ECF, complications, treatment and outcomes. All medical records were carefully filled in by the attending physicians, and then re-examined by more than two specialists. The diagnosis of ECF was based on the clinical manifestations, laboratory/imaging findings and intraoperative exploration. Results: A total of 1521 patients with ECF were enrolled, including 1099 males and 422 females, with a median age of 55 years. The top three primary diseases of ECF were malignant tumors in 626 cases (41.2%, including 540 gastrointestinal tumors, accounting for 86.3% of malignant tumors), gastrointestinal ulcers and perforations in 202 cases (13.3%), and trauma in 157 cases (10.3%). The direct causes of ECF were mainly surgical operation in 1194 cases (78.5%), followed by trauma in 156 (10.3%), spontaneous fistula due to Crohn′s disease in 92 (6.0%), radiation intestinal injury in 41 (2.7%), severe pancreatitis in 20 (1.3%), endoscopic treatment in 13 (0.9%) and 5 cases (0.3%) of unknown reasons. All the patients were divided into three groups: 1350 cases (88.7%) with simple ECF, 150 (9.9%) with multiple ECF, and 21 (1.4%) with combined internal fistula. Among the patients with simple ECF, 438 cases (28.8%) were jejuno-ileal fistula, 313 (20.6%) colon fistula, 170 (11.2%) rectal fistula, 111 (7.3%) duodenal fistula, 76 (5.0%) ileocecal fistula, 65 (4.3%) ileocolic anastomotic fistula, 55 (3.6%) duodenal stump fistula, 36 (2.4%) gastrointestinal anastomotic fistula, 36 (2.4%) esophagogastric/esophagojejunal anastomotic fistula, 29 (1.9%) gastric fistula and 21 (1.4%) cholangiopancreatiointestinal. Among all the simple ECF patients, 991 were tubular fistula and 359 were labial fistula. A total of 1146 patients finished the treatment, of whom 1061 (92.6%) were healed (586 by surgery and 475 self-healing) and 85 (7.4%) died. A total of 1043 patients (91.0%) received nutritional support therapy, and 77 (6.7%) received fistuloclysis. Infectious source control procedures were applied to 1042 patients, including 711 (62.0%) with active lavage and drainage and 331 (28.9%) with passive drainage. Among them, 841 patients (73.4%) underwent minimally invasive procedures of infectious source control (replacement of drainage tube through sinus tract, puncture drainage, etc.), 201 (17.5%) underwent laparotomy drainage, while 104 (9.1%) did not undergo any drainage measures. A total of 610 patients (53.2%) received definitive operation, 24 patients died within postoperative 30-day with mortality of 3.9% (24/610), 69 (11.3%) developed surgical site infection (SSI), and 24 (3.9%) had a relapse of fistula. The highest cure rate was achieved in ileocecal fistula (100%), followed by rectal fistula (96.2%, 128/133) and duodenal stump fistula (95.7%,44/46). The highest mortality was found in combined internal fistula (3/12) and no death in ileocecal fistula. Univariate prognostic analysis showed that primary diseases as Crohn′s disease (χ²=6.570, P=0.010) and appendicitis/appendiceal abscess (P=0.012), intestinal fistula combining with internal fistula (χ²=5.460, P=0.019), multiple ECF (χ²=7.135, P=0.008), esophagogastric / esophagojejunal anastomotic fistula (χ²=9.501, P=0.002), ECF at ileocecal junction (P=0.012), non-drainage/passive drainage before the diagnosis of intestinal fistula (χ²=9.688, P=0.008), non-drainage/passive drainage after the diagnosis of intestinal fistula (χ²=9.711, P=0.008), complicating with multiple organ dysfunction syndrome (MODS) (χ²=179.699, P<0.001), sepsis (χ²=211.851, P<0.001), hemorrhage (χ²=85.300, P<0.001), pulmonary infection (χ²=60.096, P<0.001), catheter-associated infection (χ²=10.617, P=0.001) and malnutrition (χ²=21.199, P<0.001) were associated with mortality. Multivariate prognostic analysis cofirmed that sepsis (OR=7.103, 95%CI:3.694-13.657, P<0.001), complicating with MODS (OR=5.018, 95%CI:2.170-11.604, P<0.001), and hemorrhage (OR=4.703, 95%CI: 2.300-9.618, P<0.001) were independent risk factors of the death for ECF patients. Meanwhile, active lavage and drainage after the definite ECF diagnosis was the protective factor (OR=0.223, 95%CI: 0.067-0.745, P=0.015). Conclusions The overall mortality of ECF is still high. Surgical operation is the most common cause of ECF. Complications e.g. sepsis, MODS, hemorrhage, and catheter-associated infection, are the main causes of death. Active lavage and drainage is important to improve the prognosis of ECF.

Objective To analyze the expression of VEGF,IL-33 and NO concentration after laser photocoagulation and subthreshold micropulse laser photocoagulation conventional in proliferative diabetic retinopathy (PDR) patients.Methods A case control study.The clinical data of 39 patients of PDR and 11 patients of idiopathic macular pucker (IMP) from Department of Ophthalmology,Central Theater General Hospital during November 2015 were collected in this study.PDR patients were assigned randomly into three groups.Fifteen PDR patients with 15 eyes were treated with conventional laser as group A.Thirteen PDR patients with 13 eyes were treated with subthreshold micropulse laser as group B.Eleven PDR patients with 11 eyes without any laser therapy were grouped as C.Eleven IMP patients were grouped as D.There was no difference of age (F=0.53,P=0.23),gender ratio (x2=0.55,P=0.91),body mass index (F=2.62,P=0.07),duration diabetes (F=0.29,P=0.75),glycoslated hemglobin (F=1.72,P=0.19) in four groups.All PDR patients were examined with FFA.Total protein was quantified by a bicinchoninic acid assay kit.Levels of VEGF,IL-33,NO were determined using enzyme-linked immunosorbent assay kits.Results There was no difference of total protein in four groups (F=1.78,P=0.17).Group C had a higher VEGF level than group A and B (F=7.84,P=0.002).Group A had a higher IL-33 level than group C (t=4.15,P=0.02).There was no difference of IL-33level in group B and C (t=1.34,P=0.20).Group D had a lower NO level than group A,B,C (F=38.42,P＜0.001).There was no difference of NO level in group A,B and C (F=3.29,P=0.06).Conclusions Both conventional laser photocoagulation and subthreshold micropulse laser photocoagulation can decrease vitreous VEGF level and subthreshold micropulse laser photocoagulation can induce less IL-33 level.

The threshold micropulse laser is widely used in clinical practice as a safe,non-invasive laser for avariety of macular diseases.Compared with the conventional laser therapy,the subthreshold micropulse laser is selectively absorbed by the RPE and therefore it does not cause retinal damage.To explore the therapeutic mechanism and the safety,development of threshold micropulse laser in the treatment of various common macular diseases,and further clarify its indications and advantages,which are helpful for its wider clinical application.

Objective To evaluate the application of Web problem-based learning (WPBL) mode of respiratory system integration curriculum.Methods Experimentclasses 1 and 2 of the 2014 grades of the Qiqihar Medical University were divided into control group(48 students) and experiment group (48 students).Traditional PBL teaching was conducted in control group:the contents of the case were printed and discussed with the material of each class.WPBL teaching was conducted in experiment group:autonomous learning before class,showing cases by Video,asking questions and discussion in group and reporting results in class.The teaching effect was evaluated by PBL evaluation form,questionnaire and final grade.SSPS 19.0 statistical software was used for data analysis and measurement.T test was conducted among groups.Counting data were tested by Chi-square and the results were expressed as percentage.Results The students in the experiment group were better than those of control groupin the aspects of contents understanding,course interest,clinical thinking ability,classroom atmosphere and the course attitude.The scores of PBL (16.65 ±2.82),experiment exam (8.21 ±0.44) and final grade(76.77 ± 12.31) in the experiment group were higher than those in the control group.There are statistical differences in two groups (P＜0.05).Conclusions WPBL teaching can improve students'learning interest,clinical thinking ability and improve the teaching quality of respiratory integration curriculum.