This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

OBJECTIVE: To report the clinical experience of using Ilizarov wrist joint distraction technique in the treatment of a case of rheumatoid arthritis of the wrist. METHODS: In January 2019, a 49-year-old female patient with rheumatoid arthritis of the left wrist, complicated by ulnar impaction syndrome, was admitted for treatment. Preoperatively, the active range of motion of the left wrist was as follows: extension 0°-flexion 0°, pronation 65°-supination 35°, and grip strength of 4.0 kg. The visual analogue scale (VAS) score was 9, and the Cooney wrist function score was 15, indicating poor function. As conservative treatment failed to achieve symptom relief, Ilizarov wrist joint distraction surgery was performed. Postoperatively, joint distraction was applied at 2 mm increments on postoperative days 2 and 7, in 4 separate sessions. RESULTS: Postoperative X-ray film examination at 7 days revealed a distraction of 3.6 mm in the affected wrist joint compared to the contralateral side. The external fixator was removed 2.5 months postoperatively. At 22 months postoperatively, X-ray film and MRI examinations revealed that the joint space of the left wrist had returned to near-normal, with significant reduction in joint effusion and synovial proliferation. The active range of motion of the left wrist improved to extension 15°- flexion 30°, pronation 90°-supination 90°, with a grip strength of 18.0 kg. The wrist pain VAS score decreased to 0, and the Cooney wrist function score improved to 90, indicating excellent function. At 50 months postoperatively, follow-up X-ray film, MRI, and functional assessments showed the results similar to those at 22 months. CONCLUSION Ilizarov wrist joint distraction may be a viable treatment option for rheumatoid arthritis of the wrist.
Humans ; Female ; Middle Aged ; Wrist Joint/physiopathology* ; Arthritis, Rheumatoid/physiopathology* ; Range of Motion, Articular ; Ilizarov Technique ; Treatment Outcome ; Osteogenesis, Distraction/methods*

Porcine reproductive and respiratory syndrome virus(PRRSV)mainly causes sow abor-tion,stillbirth,mummified fetus and respiratory symptoms in piglets.Since first reported in China in 1996,the virus complexity has increased significantly in more than 20 years of genetic evolution,bringing huge economic losses to the pig industry.In recent years,with the emergence of various PRRSV recombinant virus strains,preventing and controlling this epidemic became increasingly difficult.The purpose of this article is to comprehensively review the genome structure and func-tion of PRRSV,RNA virus recombination mechanism,main types of recombination,and the epi-demic status and recombination for the dominant epidemic PRRSV strains,in order to provide clues for in-depth research on gene recombination of PRRSV,thus providing the theoretical sup-port for formulating scientific prevention and control strategies.

Porcine reproductive and respiratory syndrome virus(PRRSV)mainly causes sow abor-tion,stillbirth,mummified fetus and respiratory symptoms in piglets.Since first reported in China in 1996,the virus complexity has increased significantly in more than 20 years of genetic evolution,bringing huge economic losses to the pig industry.In recent years,with the emergence of various PRRSV recombinant virus strains,preventing and controlling this epidemic became increasingly difficult.The purpose of this article is to comprehensively review the genome structure and func-tion of PRRSV,RNA virus recombination mechanism,main types of recombination,and the epi-demic status and recombination for the dominant epidemic PRRSV strains,in order to provide clues for in-depth research on gene recombination of PRRSV,thus providing the theoretical sup-port for formulating scientific prevention and control strategies.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

Objective:To explore the timing for removal of the external fixator without retraction of elongation zone during the mineralization stage in SD rat models of distraction osteogenesis (DO).Methods:Forty-two 12-week-old male Sprague-Dawley rats were randomly divided into 6 groups (groups A to F, n=7). The external fixator was removed at 1 to 6 weeks during the mineralization stage in groups A to F, respectively. To establish SD rat models of DO, after 4 threaded needles were inserted into the left femur horizontally and vertically, an external fixator was installed after osteotomy. A Kirschner wire was next inserted into the medullary cavity. After the incubation period (5 days), bone elongation lasted for 14 days until 7.0 mm was extended. Three rats were randomly selected from each group and sacrificed. After decalcification of the elongation zone, histological hematoxylin-eosin staining was performed. Radiographs were taken before removal of the external fixator and 5 weeks after removal of the external fixator for the remaining 4 rats in each group. The HE staining results, length of initial elongation zone, and retraction length of elongation zone were compared between groups. Results:HE staining showed large patches of fibrous tissue and a few immature small blood vessels in the elongation zone in group A, a small number of hypertrophic chondrocytes and fibrous junctions in the elongation zone in group B, some chondrocytes, osteocytes and fibrous tissue in the elongation zone in group C, a large number of chondrocytes on both sides of the elongation zone and fibrous connection in the center of the elongation zone in group D, a decreased number of mature hypertrophic chondrocytes and partial bone marrow in the elongation zone in group E, and a small number of chondrocytes and a partially recanalized medullary cavity with bone marrow in the elongation zone in group F. The lengths of initial elongation zone in groups A, B, C, D, E and F were, respectively, (6.98±0.14) mm, (7.02±0.18) mm, (7.02±0.08) mm, (7.02±0.11) mm, (7.01±0.18) mm and (7.00±0.12) mm, showing no statistically significant differences ( P>0.05). The lengths of retraction of elongation zone in groups A and B [(4.34±0.78) mm and (3.45±0.57) mm] were significantly longer than those in groups D, E and F [(0.16±0.17) mm, (-0.02±0.14) mm, and (0.03±0.82) mm] ( P<0.05). The timing for removal of the external fixator without retraction of elongation zone was the 4th week during the mineralization stage (group D); the healing index was 87 d/cm and the non-retraction index 67 d/cm in group D. Conclusion:In the SD rat models of DO, removal of the external fixator at 4 weeks and later during the mineralization stage may not lead to retraction of the elongation zone.

Objective:To explore the timing for removal of the external fixator without retraction of elongation zone during the mineralization stage in SD rat models of distraction osteogenesis (DO).Methods:Forty-two 12-week-old male Sprague-Dawley rats were randomly divided into 6 groups (groups A to F, n=7). The external fixator was removed at 1 to 6 weeks during the mineralization stage in groups A to F, respectively. To establish SD rat models of DO, after 4 threaded needles were inserted into the left femur horizontally and vertically, an external fixator was installed after osteotomy. A Kirschner wire was next inserted into the medullary cavity. After the incubation period (5 days), bone elongation lasted for 14 days until 7.0 mm was extended. Three rats were randomly selected from each group and sacrificed. After decalcification of the elongation zone, histological hematoxylin-eosin staining was performed. Radiographs were taken before removal of the external fixator and 5 weeks after removal of the external fixator for the remaining 4 rats in each group. The HE staining results, length of initial elongation zone, and retraction length of elongation zone were compared between groups. Results:HE staining showed large patches of fibrous tissue and a few immature small blood vessels in the elongation zone in group A, a small number of hypertrophic chondrocytes and fibrous junctions in the elongation zone in group B, some chondrocytes, osteocytes and fibrous tissue in the elongation zone in group C, a large number of chondrocytes on both sides of the elongation zone and fibrous connection in the center of the elongation zone in group D, a decreased number of mature hypertrophic chondrocytes and partial bone marrow in the elongation zone in group E, and a small number of chondrocytes and a partially recanalized medullary cavity with bone marrow in the elongation zone in group F. The lengths of initial elongation zone in groups A, B, C, D, E and F were, respectively, (6.98±0.14) mm, (7.02±0.18) mm, (7.02±0.08) mm, (7.02±0.11) mm, (7.01±0.18) mm and (7.00±0.12) mm, showing no statistically significant differences ( P>0.05). The lengths of retraction of elongation zone in groups A and B [(4.34±0.78) mm and (3.45±0.57) mm] were significantly longer than those in groups D, E and F [(0.16±0.17) mm, (-0.02±0.14) mm, and (0.03±0.82) mm] ( P<0.05). The timing for removal of the external fixator without retraction of elongation zone was the 4th week during the mineralization stage (group D); the healing index was 87 d/cm and the non-retraction index 67 d/cm in group D. Conclusion:In the SD rat models of DO, removal of the external fixator at 4 weeks and later during the mineralization stage may not lead to retraction of the elongation zone.