Objective:To assess the efficacy and safety of Tacrolimus（TAC）in combination with glucocorticosteroid（GC）for treating IgA vasculitis nephritis（IgAVN）in children.Methods:A retrospective analysis was conducted on pediatric patients who were diagnosed with IgAVN from January 2015 to January 2022 in Children's Hospital of Hebei Province.The patients presented with nephrotic-range proteinuria or persistent urine protein（>0.5g/24 h）despite adequate glucocorticoid and other treatments in patients who do not reach massive proteinuria levels.They were treated with TAC combined with GC. The following laboratory parameters were obtained for outcome assessment: 24-hour urinary protein excretion, serum albumin, serum creatinine levels, and fasting blood glucose measurements. The efficacy and adverse reactions of TAC were summarized.Results:A total of 97 children (55 males and 42 females) were included. The average age of diagnosis of IgA vasculitis was (8.65±2.46) years, and 95.9% of the children developed renal involvement within 30 days after diagnosis. Pathological examination of renal puncture: 5 cases of grade Ⅱa, 2 cases of grade Ⅱb, 31 cases of grade Ⅲa, 57 cases of grade Ⅲb, and 2 cases of grade Ⅳb.Remission rate at 3 months was 96.9%（94/97）.Three patients failed to achieve clinical remission who were treaed with other immunosuppressants.After 1, 3, 6 and 12 months of TAC treatment, the urine protein levels of 94 children were lower than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual downward trend. Serum albumin levels were higher than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual upward trend.After 3 months and 6 months of TAC treatment, the serum creatinine and fasting blood glucose of the children increased. With the remission of the disease, TAC dosage decreased, the mean values of serum creatinine and fasting blood glucose decreased after 12 months of treatment.The average treatment time of TAC was (10.8±2.6) months, the average follow-up time was (3.33±1.56) years, and the longest follow-up time was 8 years. During the follow-up period, there were no serious adverse reactions such as gastrointestinal discomfort, liver function damage and severe infection. After stopping GC and TAC treatment, 80 children got sustained remission. Conclusion:The combination of TAC and GC has been proved to be effective in treating IgAVN in children.The overall effective rate is high,and clinical remission can be achieved quickly with relatively mild adverse reactions.

Objective:To assess the efficacy and safety of Tacrolimus（TAC）in combination with glucocorticosteroid（GC）for treating IgA vasculitis nephritis（IgAVN）in children.Methods:A retrospective analysis was conducted on pediatric patients who were diagnosed with IgAVN from January 2015 to January 2022 in Children's Hospital of Hebei Province.The patients presented with nephrotic-range proteinuria or persistent urine protein（>0.5g/24 h）despite adequate glucocorticoid and other treatments in patients who do not reach massive proteinuria levels.They were treated with TAC combined with GC. The following laboratory parameters were obtained for outcome assessment: 24-hour urinary protein excretion, serum albumin, serum creatinine levels, and fasting blood glucose measurements. The efficacy and adverse reactions of TAC were summarized.Results:A total of 97 children (55 males and 42 females) were included. The average age of diagnosis of IgA vasculitis was (8.65±2.46) years, and 95.9% of the children developed renal involvement within 30 days after diagnosis. Pathological examination of renal puncture: 5 cases of grade Ⅱa, 2 cases of grade Ⅱb, 31 cases of grade Ⅲa, 57 cases of grade Ⅲb, and 2 cases of grade Ⅳb.Remission rate at 3 months was 96.9%（94/97）.Three patients failed to achieve clinical remission who were treaed with other immunosuppressants.After 1, 3, 6 and 12 months of TAC treatment, the urine protein levels of 94 children were lower than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual downward trend. Serum albumin levels were higher than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual upward trend.After 3 months and 6 months of TAC treatment, the serum creatinine and fasting blood glucose of the children increased. With the remission of the disease, TAC dosage decreased, the mean values of serum creatinine and fasting blood glucose decreased after 12 months of treatment.The average treatment time of TAC was (10.8±2.6) months, the average follow-up time was (3.33±1.56) years, and the longest follow-up time was 8 years. During the follow-up period, there were no serious adverse reactions such as gastrointestinal discomfort, liver function damage and severe infection. After stopping GC and TAC treatment, 80 children got sustained remission. Conclusion:The combination of TAC and GC has been proved to be effective in treating IgAVN in children.The overall effective rate is high,and clinical remission can be achieved quickly with relatively mild adverse reactions.

ObjectiveTo observe the distribution of traditional Chinese medicine （TCM） syndrome types in advanced pancreatic cancer patients， and explore the association between median survival time and different TCM syndromes and different intervention times of Chinese herbal medicine （CHM）. MethodsThe clinical data of 136 advanced pancreatic cancer patients who have received CHM for more than 3 months were collected retrospectively， including gender， age， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， western medicine treatment methods， TCM diagnosis and treatment information， and survival time. The Kaplan-Meier （KM） estimator was used， and the median survival time of patients was calculated. The TCM syndrome type of each patient was judged， and the main single syndrome types and compound syndrome types were summarized. The median survival time was compared among different compound syndrome types. The patients were further divided into the group of those having received CHM ≥6 months and those having received CHM ＜6 months. Whether receiving CHM ≥6 months was taken as the grouping variable， while the matching variables were age， gender， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， surgery， chemotherapy， and radiotherapy when propensity score matching was performed， and the difference in median survival time between the two groups of patients before and after matching was compared. ResultsFor 136 cases of advanced pancreatic cancer， the top five single syndromes were spleen qi deficiency， liver blood stasis， liver qi stagnation， spleen dampness， and liver heat. The main compound types were liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， liver constraint， qi stagnation and spleen deficiency syndrome， spleen-stomach yang deficiency and blood stasis syndrome， and spleen deficiency and dampness-heat internal accumulation syndrome. The overall median survival time before and after matching was 12.47 （7.70，17.10） months and 13.77 （8.83，17.20） months， respectively， and was significantly higher in the group treated with CHM ≥ 6 months than that treated with CHM ＜6 months （P＜0.05）. Among the 136 patients before matching， the median survival time of patients with spleen deficiency and dampness-heat internal accumulation syndrome was longest ［16.23 （14.17，19.40） months］， while that of patients with spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［7.33 （5.80，12.83） months］. For patients with liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， and spleen-stomach yang deficiency and blood stasis syndrome， those having received CHM ≥ 6 months have much longer median survival time than those having received CHM ＜6 months （P＜0.05）. Among the 108 patients after matching， the median survival time of those with spleen deficiency and dampness-heat internal accumulation syndrome was the longest ［15.23 （7.67，18.27） months］， while that of spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［8.80 （6.90，16.17） months］. For patients with liver-gallbladder dampness-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome， the median survival time was higher in the group treated with CHM ≥ 6 months treated with CHM ＜6 months （P＜0.05）. ConclusionAfter treatment with CHM， advanced pancreatic cancer patients with spleen deficiency and damp-heat internal accumulation had a better prognosis， while those with spleen-stomach yang deficiency and blood stasis had a worse prognosis. Treatment with CHM ≥ 6 months could extend the median survival of advanced pancreatic cancer patients with liver-gallbladder damp-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome.

According to the theory of qi channels， we explored the relationship of the method of invigorating blood and regulating tumour immunity， to provide ideas and methods for traditional Chinese medicine for regulating tumour immunity and anti-tumour metastasis. It is believed that qi channels are closely related to tumour immunity， and qi channels are equivalent to immune networks such as immune cells and immune factors with anti-tumour immunity in the tumour immune micro-environment. Combined with the physiological function and pathological characteristics of qi channels， it is proposed that the pathogenesis of qi channels-related disease due to qi channels failing to govern， blood stasis obstructing， and qi channels deficiency and stagnation as the basis for the occurrence of tumour immunosuppression and metastasis， and that qi channels constraint and stagnation as the condition for the occurrence of tumour immunosuppression and metastasis. In view of the pathomechanism of tumour immune escape caused by qi channels failing to govern， it is proposed that the therapeutic principle of regulating qi and channels to regulate tumour immunity by invigorating blood circulation method could be "performing functions when there is free flow， reaching the expectation when balanced"， and the key of treatment is to regulate qi and channels， unblock the collaterals to dispel stasis.

This article analyzes the limitations of traditional medical theory teaching, and proposes the strategies for cultivating medical students' autonomous learning ability, i.e., informatization-based flipped classroom, problem-oriented teaching, mind mapping training, semi-open book examination, exploitation of the clinical and scientific thinking, and practice activities of medical humanities. The strategies of "problem oriented teaching" and "mind mapping training" were integrated into the practice teaching of hematology. Compared with the traditional medical teaching mode, students' feedback after class showed that the teaching mode incorporating new cultivation strategies was more conducive to the improvement of students' self-learning ability ( P = 0.008), and their satisfaction with teaching mode, learning interest, and self-learning ability were all improved. Thus, the appropriate application of the above strategies can help improve students' autonomous learning ability and optimize the effect of medical theory teaching.

Cancer-related fatigue (CRF) belongs to the category of "consumptive disease" in TCM, and its occurrence is based on "internal deficiency" of the body causing by the tumor. Its nature is intermingled deficiency and excess. Its pathogenesis is the deficiency of qi, blood, yin and yang and zang-fu viscera dysfunction caused by disorders of "rise and fall of middle qi" and kidney origin depletion. The theory of "treating overstrain syndrome with warming methods" originates from Huang Di Nei Jing, which proposes that warming methods are the basic methods of treating consumptive disease. Therefore, starting from the cause and pathogenesis of CRF, this article sorted out the theoretical origin of "treating overstrain syndrome with warming methods", and discussed the clinical application of warming methods for the treatment of CRF combining with modern clinical research, with the purpose to provide references for clinical practice.

Femoral acetabular impingement (FAI) syndrome is a motion-related clinical disorder of the hip joint, resulting in cartilage lesions frequently. The pattern and natural history of these cartilage lesions vary with types of FAI, each bearing unique gross appearance and injury mechanism. On the basis of available evidence, this paper reviews the progress of the FAI-related acetabular cartilage lesions in pathogenesis, diagnosis and treatment. Cam-type FAI is always closely associated with acetabular cartilage lesions and early-onset of hip osteoarthritis. However, the reason why acetabular cartilage developed into osteoarthritis in FAI of Cam-type is unknown. In addition to the direct mechanical impingement and the vulnerable anatomic base of chondrolabral junction, stress change from abnormal movement or anatomical morphology will lead to the change of biomechanical environment, causing a chronic-recurrent inflammation in articular cartilage. The preoperative diagnosis of acetabular cartilage lesions depends on a triad of symptoms, clinical signs and imaging findings. 1.5 T magnetic resonance arthrography and 3.0 T magnetic resonance imaging are equally valued in objectively diagnosing cartilage lesions. Final diagnosis relies on surgical exploration, however, there is no consensus on how cartilage lesions should be reported, including the description of extent, location, pattern and grade. Using Beck classification of clock-face method to describe lesions observed in surgery is recommended at present. Most treatment methods of FAI-related acetabular cartilage lesions are borrowed from treating cartilage lesions in knee joints. Conservative treatment includes rest, activity modification, nonsteroidal anti-inflammatory medications and physical therapy. Surgery is an option if conservative treatment of at least 6 months fails. The surgical procedures commonly include chondroplasty, microfracture and enhanced microfracture, autologous matrix-induced chondrogenesis, autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, osteochondral transplantation and other cartilage repair techniques. However, there is no consensus on the standardized treatment of FAI-related acetabular cartilage lesions for lacking evidence-based guidance currently.

ObjectiveTo explore the effect of tetramethylpyrazine （TMP） on the vascular mimicry （VM） of non-small cell lung cancer A549 stem cell-like cells （CSLCs） in hypoxic state， and on the expression of hepatocyte growth factor （HGF）/mesenchymal-epithelial transition factor （c-Met）. MethodSerum-free sphere culture method was used to separate and enrich A549 CSLCs， and flow cytometry to detect the expression of stem cell marker CD44⁺/CD24^-/low. CoCl₂ was employed to induce hypoxia model. Cell counting kit-8 （CCK-8） assay was employed to examine the influence of 100， 200， 400， 800， 1 600， and 3 200 μmol·L^-1 TMP on the viability of A549 CSLCs. The low， medium， and high concentration （100， 200， 400 μmol·L^-1） of TMP that did not significantly affect the viability of A549 CSLCs was selected for subsequent experiments. Tube formation assay was used to detect the effect of different concentration of TMP on the formation of A549 CSLCs VM under hypoxia condition， and Western blot was applied to measure the expression of HGF/c-Met. ResultThe CD44⁺/CD24^-/low expression ratio of the isolated and enriched CSLCs was （80.3±0.21）%， which was significantly higher than that of the A549 group （P<0.01）. Compared with the control group， TMP groups showed increase in the inhibition rate of CSLCs， particularly the 24 h TMP （800， 3 200 μmol·L^-1） groups and the 48 h TMP （1 600， 3 200 μmol·L^-1） groups （P<0.05）. Compared with blank group and Bevacizumab （Bev） group， each concentration of TMP decreased the number of tubes formed and intersections （P<0.01）. The number of tubes formed and intersections decreased in TMP groups compared with that in the SU11274 group， particularly the 200 μmol·L^-1 TMP group （P<0.05） and 400 μmol·L^-1 TMP group （P<0.01）. Levels of HGF and c-Met in all TMP groups were down-regulated compared with those in the blank group （P<0.05， P<0.01）. ConclusionTMP can inhibit the formation of VM in A549 CSLCs in vitro under hypoxia condition which may act by regulating HGF/c-Met related signaling pathways.

Objective To observe the effects of different doses of Sappan Lignum and Chuanxiong Rhizoma on tumor stem cells marker ABCG2 in vivo. Methods Sphere cells obtained from serum culture were inoculated in nude mouse armpit, which were randomly divided into 5 groups: control group, Sappan Lignum high- and low-dose groups, and Chuanxiong Rhizoma high- and low-dose groups. Each medication group was given relevant medicine for gavage. 21 days later, inhibition tumor rate and ABCG2 protein and mRNA expression were detected with confocal microscope, Western blot, and RT-PCR. Results The sphere cells obtained from serum free culture had the abilities of cancer stem cells, such as proliferation, anti-aptosis and high expression of cancer stem cells markers. Chuanxiong Rhizoma high- and low-dose groups could inhibit tumor growth (P<0.05), and the inhibitory rate of Chuanxiong Rhizoma low-dose group was higher than the Chuanxiong Rhizoma high-dose group. Sappan Lignum high- and low-dose groups inhibited tumor growth without statistical significiance (P>0.05). Compared with the control group, Chuanxiong Rhizoma low-dose group could significantly inhibit the expression of resistant protein of ABCG2. Sappan Lignum high- and low-dose groups could not inhibit the protein expression of ABCG2. Each medication group up-regulated the mRNA expression of ABCG2 except for Chuanxiong Rhizoma low-dose group. Conclusion Low dose of Chuanxiong Rhizoma can inhibit the expression of ABCG2 protein levels, which can be the targeting killer for cancer stem cells.

Objective To observe the effects of dredging collaterals and activating blood worm Chinese materia medica on angiogenesis related factors of lung cancer in hypoxic environment. Methods The lung cancer A549 cells were cultured in vitro to simulate tumor hypoxia microenvironment by the hypoxia workstation, and different concentrations of Scorpio, Scolopendra and Gecko medicated serum were added. MTT method was used to detect cell proliferation and screen the best medicine concentration and duration of action. Lung cancer A549 cells were administrated by the three kinds of medicated serum, and cells were collected and supernatant was cultured. Contents of VEGF, TGF-β1, and bFGF were detected by ELISA. Results Three kinds of medicated serum had the inhibitory effect on both added normoxia and hypoxia in cultured A549 lung cancer cells. 7.5% concentration of medicated serum was selected, and 24 h later were used in later experiments. Scorpio, Scolopendra and Gecko medicated serum can more reduce the contents of VEGF, TGF-β1 and bFGF in the supernatant of A549 cell compared with the control group (P<0.05, P<0.01). Conclusion Dredging collaterals and activating blood worm Chinese materia medica had inhibitory effect on cancer cells and the regulation of angiogenesis related cytokines in the condition of normoxia and hypoxia.