The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

Infectious chronic refractory wounds are common in the department of dermatology,and have a great influence on the quality of life of patients.Their incidence is increasing year by year.The pathogensis of infectious chronic refractory wounds is due to the exuberance of pathogenic heat and toxin,disharmony between nutritive qi and defensive qi,and imbalance of zang-fu organs,which is related with the theory of qi-fluid and sweat pores.Therefore,it is proposed that stagnation and obstruction of sweat pores contribute to the pathological basis for the onset of infectious chronic refractory wounds,and therapeutic principle of opening sweat pores was presented.In the medication view of treating the skin diseases with the skin-related Chinese medicinals,skin-related Chinese medicinals are good at treating skin diseases,and consequently the application of skin-related Chinese medicinals to open sweat in treating infectious chronic refractory wounds was discussed.It is suggested that for the treatment of infectious chronic refractory wounds due to pathogenic fire-toxin accumulation in sweat pores,therapy of clearing heat and expelling fire to open sweat pores should be exployed,and skin-related Chinese medicinals such as Phellodendri Chinensis Cortex,Dictamni Cortex and Fraxini Cortex can be selected;for the treatment of infectious chronic refractory wounds due to blood-stasis stagnation in sweat pores,therapy of cooling and activating blood to open sweat pores should be exployed,and skin-related Chinese medicinals such as Moutan Cortex and Lycii Cortex can be selected;for the treatment of infectious chronic refractory wounds due to wind and dampness obstructing sweat pores,therapy of expelling wind and eliminating dampness to unblock sweat pores should be exployed,and skin-related Chinese medicinals such as Acanthopanacis Cortex,Citri Reticulatae Pericarpium,and Poriae Cutis can be selected;for the treatment of infectious chronic refractory wounds due to healthy qi deficiency resulting in the obstruction of sweat pores,therapy of invigorating spleen and tonifying kidney to nourish sweat pores should be exployed,and skin-related Chinese medicinals such as Cinnamomi Cortex,Eucommiae Cortex,and black soybean testa(Testa Glycinea Macids)can be chosen.Guided by the theory of qi-fluid and sweat pores,this paper explored the application of skin-related Chinese medicinals in the treating infectious chronic refractory wounds,which provides theoretical basis for such an approach,enriches the theory of traditional Chinese medicine for the treatment of infectious chronic refractory wounds,and expands the clinical application of the theory of sweat pores.

Objective To analyze the effect of extracorporeal shock wave assisted drug therapy on clinical outcomes of patients with temporomandibular disorders(TMD).Methods A total of 86 TMD patients in our hospital from September 2018 to September 2019 were included and divided into group A(n=43)and group B(n=43)by random number table method.Group A(n=43)received oral glucosamine hydrochloride tablets on the basis of conventional treatment;group B(n=43)received extracorporeal shock wave therapy on the basis of group A.The pain degree,maximum mouth opening,temporomandibular joint function,temporomandibular joint bounce times,life quality and occurrence of adverse reactions were compared between the two groups.Results Compared with that before treatment,the visual analogue scale(VAS)scores,maximum mouth opening,temporomandibular joint dysfunction index(DI),palpation index(PI),Fricton craniomandibular index(CMI)level,joint bounce times and oral health impact scale(OHIP-14)score of two groups were significantly improved(P＜0.05),and all indexes in group B were significantly better than those in group A(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Extracorporeal shock wave assisted drug therapy can effectively reduce joint bounce in TMD patients,relieve patients'pain,improve patients'life quality and temporomandibular joint function,and has good safety.

Objective:To explore the effect of modified Chushi Weiling Decoction combined with fire acupuncture in the treatment of chronic eczema with spleen deficiency and dampness syndrome.Methods:A total of 106 patients with chronic eczema who met the inclusion criteria from January 2018 to January 2020 in Shandong Taishan hospital were randomly divided into two groups by random number table method, with 53 patients in each group. The control group was treated with loratadine tablets and compound glycyrrhizin tablets, and the observation group was treated with modified Chushi Weiling Decoction combined with fire acupuncture. Both groups were treated for 8 weeks and followed up for 12 months. TCM syndrome scores were performed before and after treatment, Eczema area and severity index (EASI) was used to assess the severity of eczema, and pruritus was assessed by pruritus VAS scale. The serum IgE level was detected by nephelometry, and eosinophils (EOS) count was detected by automatic hematology analyzer. The adverse events and recurrence were recorded and the clinical response rate was evaluated.Results:The response rate was 94.34% (50/53) in the observation group and 77.36% (41/53) in the control group. There was significant difference between the two groups ( χ2=6.29, P=0.012). After treatment, the score of TCM syndrome, EASI and VAS of pruritus in the observation group were significantly lower than those in the control group ( t values were 11.97, 6.31 and 10.61 respectively, all Ps<0.001). After treatment, the serum IgE level [(57.19±7.54) IU/ml vs. (81.55±12.08) IU/ml, t=12.45], EOS count [(310.54± 52.84) ×10 6/L vs. (465.51±58.04) ×10 6/L, t=14.37] in the observation group were significantly lower than those in the control group ( P<0.01). The incidence of adverse events was 15.09% (8/53) in the control group and 3.77% (2/53) in the observation group, and there was significant difference between the two groups ( χ2=3.98, P=0.046). The recurrence rate was 6.00% (3/50) in the observation group and 21.95% (9/41) in the control group, and there was significant difference between the two groups ( χ2=5.01, P=0.025). Conclusion:Modified Chushi Weiling Decoction combined with fire acupuncture can improve the skin lesions and itching symptoms, improve the clinical efficacy, reduce the long-term recurrence rate of patients with chronic eczema with spleen deficiency and dampness syndrome safely.

Objective To analyze the failure and processing methods of helical tomotherapy multileaf collimator (MLC) and summarize relevant maintenance experience,aiming to accurately identify the faulty parts,shorten the downtime and enhance the work time.Methods The failure data of the helical tomotherapy MLC system in the past 48 months were analyzed to identify the common faulty parts,causes and processing methods.Results During the previous 48 months,the MLC failure occurred for 20 times,11 times for air compressor failure,4 times for position verification board failure,twice for leaf driver failure,twice for cushion valve failure and once for the slip of leaf position verification rod.The MLC failure was significantly correlated with the humidity of high-pressure gas.The work time of machine exerted significant effect upon the service time of MLC parts.Conclusions The structure of the helical tomotherapy MLC system is complex.The high-intensity work increases the failure rate.The humidity of high-pressure gas affects the normal operation of the MLC equipment.The faulty parts can be identified,the downtime can be reduced and the work time can be enhanced by summarizing the experience of MLC maintenance.

At present,traditional Chinese medicine(TCM) has attracted more and more attention from the international community.The demand for TCM is increasing in the world.The hidden dangers of potential quality and safety of TCM are also becoming increasingly prominent.Aflatoxin contamination has become one of the important factors affecting the safety of Chinese herbal medicines,and it will fundamentally affect human health and life safety.A variety of methods are used to reduce aflatoxins,however,there are few suitable methods that can be widely used in the cost-effective and large-scale promotion of Chinese herbal medicines.Therefore,it is of great significance to continue to study measures to solve the pollution problems of Aspergillus flavus and its toxins.This article summarizes the hazards and contamination status of aflatoxin,the prevention and control of the growth of A. flavus, and the measures for reducing aflatoxin,and looks ahead to the future prevention and control of A. flavus and its toxins,aiming at providing ideas for the pollution problem of A. flavus and its toxin,to ensure the quality of Chinese herbal medicines,so as to ensure clinical safety medication.

Objectives: To explore weather oxygen uptake efficiency slope (OUES) may predict the prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods: The consecutive newly diagnosed IPAH patients in our hospital from 2010-11 to 2015-06 were prospectively enrolled and regular follow-up study was conducted to record cardiovascular events (death and lung transplantation). Kaplan–Meier curve, uni- and multivariate Cox regression analysis were performed to assess the survival rate in relevant patients. Results: A total of 210 IPAH patients at the mean age of (32±10) years were finished cardiopulmonary exercise test (CPET) and received regular follow-up study including 159 female. There were 31 patients died and 1 received lung transplantation over 41 months follow-up period. OUES was positively related to peak oxygen uptake (VO2)/body weight (r=0.71, P<0.0001). Multivariate analysis demonstrated that OUESI and NT-proBNP could independently predict the prognosis of IPAH patients. The 5-year survival rate in patients with OUESI≤0.52 L/(min?m2) was lower than those with OUESI>0.52 L/(min?m2) (41.9% vs 89.8%), P<0.0001.Conclusion: OUES as a submaximal CPET parameter may well predict the prognosis in IPAH patients.

Objective:To explore the effect of red blood cell distribution width (RDW) on long-term follow-up study in patients with acute pulmonary thromboembolism (APE).
Methods:A total of 214 consecutive patients with the first episode of APE admitted in our hospital from 2009-01 to 2012-12 were enrolled. The patients were divided into 2 groups:RDW≤15%group, n=202 and RDW>15%group, n=12. Baseline RDW was measured at admission, the follow-up study was conducted at 3, 6, 12 months thereafter, and then at once per year. The major primary end point was chronic thromboembolic pulmonary hypertension (CTEPH). The independent predictor for CTEPH occurrence was studied by uni-and multivariate logistic regression analysis and the predictive capability of RDWwas evaluated by ROC curve.
Results: All patients ifnished the follow-up study at the mean of (31±17) months. The overall occurrence rate of CTEPH was 7.5% (16/214), which was higher in RDW>15% group than that in RDW≤15% group (33.3% vs 5.9%, P=0.002). Multivariate logistic regression analysis indicated that with adjusted clinical data and other predictors, RDW>15%was still the strong predictor for CTEPH occurrence (OR=7.916, 95%CI 1.474-42.500, P=0.016). Adding RDW to the evaluating model, the predictive capability could be signiifcantly improved by ROC curve (AUC increased from 0.856 to 0.901, P<0.01).
Conclusion: Elevated RDW is the independent predictor for CTEPH occurrence in APE patients, which is helpful to estimate the prognosis and treatment strategy in APE patients.

Objective To explore the role of hydrogen sulfide (H 2S ) in acute liver injury induced by crush-ing hind lim bs of rats. Methods The rats w ere random ly divided into the follow ing groups:control, crush-ing, H 2S donor sodium hydrosulfide (NaHS) + crushing, H 2S inhibitor propargylglycine (PAG ) + crush-ing group. The acute liver injury m odel w as established by crushing the hind lim bs of rats w ith standard w eight. R ats w ere sacrificed at 30 m in and 120 m in after the crush. The activities of serum aspartate am inotransferase (AST) and alanine am inotransferase (ALT) w ere m easured by colorim etric m ethod, and the content of H 2S in plasm a and the contents of m alondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the liver and the activity of H 2S generating enzym e (cystathionine γ-lyase, CSE) w ere deter-m ined by chem ical m ethod. The expression of CSEm R N Ain liver w as detected by R T-PCR . Results For crush injury group, the levels of ASTand ALTin serum , MDAand protein carbonyl in liver in-creased. The levels of GSH, CSE, CSEm R N Ain liver and H 2S in serum decreased. The adm inistration of NaHS before lim bs crush could attenuate the changes of liver injury, but the pre-treatm ent w ith PAG could exacerbate the changes. Conclusion The decrease of H 2S production could involve in m ediating the acute liver injury induced by traum atic stress in rats.