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.

Yigongsan， derived from QIAN Yi’s Key to Therapeutics of Children’s Diseases in the Song Dynasty， is a classic pediatric prescription that is included in the Catalogue of Ancient Classic Prescriptions （the Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine in 2022. This paper verifies and analyzes the historical origin， composition， dosage， processing， decoction method and efficacy of Yigongsan by systematically combing ancient books and modern documents. As a result， Yigongsan is composed of five herbs： Panax ginseng， Poria cocos， Atractylodes macrocephala， Citrus reticulata and Glycyrrhiza uralensis， of which P. cocos should be peeled， A. macrocephala is fried with soil， G. uralensis is roasted with honey while P. ginseng and C. reticulata are raw products. According to the dosage of ancient and modern times， each medicinal herb must be ground into fine powder， 1.6 g for each， added with 300 mL of water， 5 pieces of Zingiber officinale， and 2 Ziziphus jujuba， decocted together to 210 mL， and taken before meals. In ancient books， Yigongsan is used to treat vomiting， diarrhea， spleen and stomach deficiency， chest and abdominal distension， and lack of appetite， etc. Modern research showed that Yigongsan could also be used in the diseases of immune system， respiratory system， blood system， etc.， involving infantile anorexia， asthma， anemia， tumors and so on.

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 observe the electrophysiological characteristics of anterior cingulate cortex(ACC)neurons in mice with orofacial pain induced by complete Freund's adjuvant(CFA).Methods Eighteen mice were randomly divided into Sham group and CFA group.CFA was injected under the right facial beard pad in mice to construct a model of orofacial pain.Normal saline was injected in the Sham group.Von-Frey filament was used to detect the threshold of mechanical orofacial pain.The excitatory postsynaptic current(EPSC)and action potential(AP)of ACC neurons were observed in the Sham group and CFA group by patch clamp method.Results The threshold of mechanical pain in the CFA group was significantly lower than that in the Sham group after injection(P<0.05).The frequency and amplitude of the EPSC of ACC neurons in the CFA group were significantly higher than those in the Sham group(P<0.05).AP results showed that when the stimulus current was 100,125,150,175 and 200 pA,the discharge frequency of ACC neurons in the CFA group was significantly higher than that in the Sham group(P<0.05).Conclusion The activity of ACC neurons increases in the development and prgression of orofacial pain in mice and may be closely related to the formation of orofacial pain.

Black triangle caused by gingival papilla loss is an ordinary clinical problem. Gingival recession and alveolar bone absorption in the area of gingival papilla lead to the increase of the vertical distance from the adjacent contact point to the alveolar ridge. Periodontal soft tissue grafts play a certain role in the gingival papilla reconstruction. This paper reviewed the effects of soft tissue grafts on the reconstruction of gingival papilla loss through following several aspects, summary of gingival papilla loss, gum soft tissue reconstruction, biological and chemical factors influencing gingival papilla reconstruction. The role of coronally advanced flap surgery, semilunar coronal repositioned flap surgery, subepithelial connective tissue graft, pedicle flap graft, envelop flap graft and tunnel technique were evaluated.

Objective:To study the relationship between IL-1β and TNFα expression and cell apoptosis in gingival tissue of the subjects with diabetes associated periodontitis(DAP).Methods:20 cases of DAP(group DAP) and 20 cases of health controls(group H)were included.The cell apoptosis and the ultrastructural changes in gingival tissue were observed by Tunnel staining and transmission electron microscope (TEM).IL-1β and TNFα expression in gingival tissue were detected by immunohistochemical staining.SBI,GI,PD and AL of the subjects were measured.The relationship between the level of IL-1β,TNFα and the cell appotosis was analyzed.Results:Apoptosis was obvious in prickle cells and basal cells of gingival tissue of DAP group.The percentage of apoptosis cells of DAP group was significantly higher than that of group H(P＜0.01).The expression of IL-1β and TNFα in group DAP was significant higher than that of group H (P＜0.01),and the mainly positive expression cells were macrophages,plasmocytes and lymphocytes.Conclusion:IL-1β and TNFα play a role in cell apoptosis in the gingival tissue of the patients with DAP.

Objective To compare the sensitivity of the fluorescent quantitation PCR method (fluorescence quantitative method for short)and the gene chips typing method (gene chips method for short)in testing human papilloma virus(HPV) .Methods 305 outpatients in the gynecological clinic of the hospital from February 2010 to February 2013 were selected as the research subject . Then the cervical exfoliated cells were collected and detected HPV by the fluorescence quantitative method and the gene chips meth-od respectively .Those cases with inconsistent results were confirmed by the PCR sequencing method .305 cases were performed the liquid based cytology test .Results The sensitivity of the fluorescence quantitative method in detecting HPV was 33 .8% and which of the gene chips method was 37 .6% .The two methods had a higher conformance .The HPV infection rate was increased with the increase of cervical exfoliated cell atypia .Conclusion The fluorescence quantitative method and the gene chips method have a higher conformance .The sensitivity of the gene chips method is higher .The severity degree of cervical cytological change is positively cor-related with the HPV infection .

This study is to establish an artificial neural network (ANN) for predicting blood tacrolimus concentration in liver transplantation recipients. Tacrolimus concentration samples (176 samples) from 37 Chinese liver transplantation recipients were collected. ANN established after network parameters were optimized by using momentum method combined with genetic algorithm. Furthermore, the performance of ANN was compared with that of multiple linear regression (MLR). When using accumulated dose of 4 days before therapeutic drug monitoring (TDM) of tacrolimus concentration as input factor, mean prediction error and mean absolute prediction error of ANN were 0.02 +/- 2.40 ng x mL(-1) and 1.93 +/- 1.37 ng x mL(-1), respectively. The absolute prediction error of 84.6% of testing data sets was less than 3.0 ng x mL(-1). Accuracy and precision of ANN are superior to those of MLR. The correlation, accuracy and precision of ANN are good enough to predict blood tacrolimus concentration.
Adult ; Aged ; Drug Monitoring ; methods ; Female ; Humans ; Immunosuppressive Agents ; blood ; Linear Models ; Liver Transplantation ; Male ; Middle Aged ; Neural Networks (Computer) ; Tacrolimus ; blood