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 investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Objective:To investigate the incidence and risk factors of coma in patients with hypoglycemia (≤3.9 mmol/L).Methods:A retrospective study was conducted. Patients aged 20 years and older with blood glucose levels ≤3.9 mmol/L, and measured by emergency physicians from January 2020 to December 2022 were collected. Baseline patient data, clinical values collected on-site, and treatment outcomes were analyzed. The Glasgow Coma Scale (GCS) was used to determine if patients were comatose, with GCS ≤8 classified as the coma group and GCS >8 as the non-coma group. Further analysis was conducted on the resuscitated coma group to identify factors affecting patient recovery. Patients were divided into eight age groups, seven time periods within 24 h, and six blood glucose level groups to calculate the incidence of coma. A multivariate logistic regression model was constructed to analyze independent risk factors for coma in hypoglycemic patients.Results:A total of 754 patients with blood glucose levels ≤3.9 mmol/L were collected, with 425 cases of coma and 329 non-coma cases, resulting in a coma probability of 56.37% (95% CI: 52.82%-59.91%). Patients in the coma group were older ( P<0.001) and had a higher prevalence of diabetes compared to the non-coma group (82.12% vs. 67.78%, P<0.001). The age of all patients was (73.05±15.20) years, with the 61-90 years age groups being the most prone to hypoglycemia and coma. In terms of time distribution, the high-incidence periods for hypoglycemia and coma were 0-6 o’clock, 6-9 o’clock, and 14-18 o’clock. The primary causes of hypoglycemia included reduced energy intake after insulin injection (12.07%), improper use of insulin (6.37%), and reduced energy intake (6.23%), with 71.09% of cases having unknown causes. Additionally, 18.44% of patients used insulin before the onset of hypoglycemia, with a higher proportion in the coma group compared to the non-coma group (22.12% vs. 13.68%, P=0.003). The initial blood glucose level of all patients was (2.13±0.85) mmol/L, with lower levels observed in the coma group compared to the non-coma group ( P<0.001). The probabilities of coma occurrence corresponding to blood glucose levels were: 1.1-1.5 mmol/L (72.97%), 1.6-2.0 mmol/L (68.90%), 2.1-2.5 mmol/L (54.10%), 2.6-3.0 mmol/L (38.20%), 3.1-3.5 mmol/L (37.50%), and 3.6-3.9 mmol/L (19.40%). Multivariate logistic regression analysis indicated that age ( OR=1.021, 95% CI: 1.010-1.033, P<0.001), insulin use before onset ( OR=1.948, 95% CI: 1.142-3.323, P=0.014), and blood glucose concentration ( OR=0.426, 95% CI: 0.347-0.522, P<0.001) were independent predictors of coma in hypoglycemic patients. The investigation revealed that after intravenous injection of 50% glucose solution, 215 of 425 coma patients regained consciousness (50.58%), and the recovery time was (18.43±9.09) min. Patients in the recovery group were younger and had lower initial blood glucose levels compared to the non-recovery group (both P<0.05), while recovery group re-measured blood glucose levels were higher than those in the non-recovery group ( P=0.002). Conclusions:The probability of coma in hypoglycemic patients was high, with insulin use being a common trigger. Proper use of insulin is essential to prevent hypoglycemia and coma.

Objective:To construct a simple model of arteriovenous fistula classification,and to achieve the classification of arteriovenous fistula in hemodialysis patients.Methods:The study was a retrospective analysis, a total of 304 hemodialysis patients with internal fistula in People′s Hospital of Deyang City from January 2016 to January 2021 were selected by convenience sampling method,depending on whether the internal fistula was dysfunctional, patients were divided into 64 in the internal fistula failure group and 240 in the internal fistula patency group. Independent influence factors and their regression coefficient were obtained by single-factor analysis and logistic regression analysis, The risk score formula was established based on the regression coefficient to form a simple model of internal fistula classification.The model was evaluated by receiver operating characteristic curve and the scoring criteria for internal fistula classification was determined.Results:Logistic regression analysis showed that diabetes mellitus, hypotension, age≥60 years old, compression time≥30 min, blood phosphorus>1.78 mmol/L, triglyceride>1.71 mmol/L and fibrinogen>4 g/L were independent influencing factors of internal fistula failure (all P<0.05).The area under the receiver operating characteristic curve was 0.858(95% CI 0.789-0.928, P<0.01), and the best critical value of the internal fistula classification was 7.5, the sensitivity was 80.4% and the specificity was 84.8%. Conclusions:By obtaining the predictors of internal fistula failure, conducted the risk score, and constructed a simple model of internal fistula classification, which can effectively predicted the risk of internal fistula failure. It is conducive to the implementation of internal fistula classification management and the puncture of corresponding grade, to ensure the pathway safety of patients.

Objective:To investigate the effect of scar uterus on assisted reproduction treatment strategy.Methods:From January 1, 2017 to December 31, 2017, 109 cases of scar uterus group and 63 cases of vaginal delivery history group who underwent in vitro fertilization-embryo transfer (IVF-ET) assisted pregnancy fresh embryo transfer in our hospital were retrospectively analyzed. Results:⑴ There was no significant difference in the total amount of gonadotropin (Gn) and the total days of GN in patients <35 between scar uterus group and the vaginal delivery history group ( P>0.05), but there were significant differences in the number of oocytes, mature oocytes, two pronucleus (2PN) and excellent embryos between the scar uterus group and the vaginal delivery history group ( P<0.05). When the age was ≥35 years old, there was no significant difference in the total number of GN, the total days of GN, the number of oocytes obtained, the number of mature oocytes, the number of 2PN and the number of excellent embryos between the two groups ( P>0.05). ⑵ There were no statistically significant differences in clinical pregnancy rate and embryo implantation rate between the two groups of patients < 35 years old, no matter single embryo transplantation or double embryos transplantation. When transplant two embryos, the clinical pregnancy rate and embryo implantation rate in the scar uterus group were slightly lower than those in the vaginal delivery history group (57.57% vs 71.05% and 39.39% vs 47.37%, respectively), but with no significant difference ( P>0.05). There were no statistically significant differences in the clinical pregnancy rate and embryo implantation rate between single embryo transplantation and double embryo transplantation in patients≥35 years old ( P>0.05). ⑶ There were no statistically differences in biochemical pregnancy rate, early abortion rate, preterm birth rate and average newborn weight between the scar uterus group and the vaginal delivery history group ( P>0.05). Conclusions:Cesarean section may affect the ovarian function. For patients with previous cesarean section, early evaluation of ovarian function is recommended. Single embryo transfer does not reduce the outcome in IVF-ET. It is recommended to perform single embryo transfer for patients with scar uterus to reduce the risk during pregnancy of twin pregnancy.

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Brain Edema ; drug therapy ; etiology ; Brain Injuries, Traumatic ; complications ; drug therapy ; Gene Expression Regulation, Enzymologic ; drug effects ; Indazoles ; pharmacology ; therapeutic use ; MAP Kinase Signaling System ; drug effects ; Matrix Metalloproteinase 9 ; genetics ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Blood-Brain Barrier ; Brain Edema ; Brain Injuries, Traumatic ; MAP Kinase Signaling System ; Matrix Metalloproteinase 9 ; Rats ; Rats, Sprague-Dawley

Objective To assess the effects of artificial cycle after long-acting gonadotropin-releasing hormone (GnRH) agonist down regulation scheme and artificial cycle only scheme in preparation of endometrium before frozen embryo transfer in polycystic ovary syndrome (PCOS) patients on pregnancy outcome.Methods A retrospective analysis was made on the frozen embryo transfer of 132 PCOS patients in the reproductive center of Hunan Maternal and Child Health Hospital from November 2016 to October 2017.The patients were divided into GnRH-a down regulation + artificial cycle group (n =66) and simple artificial cycle group (n =66) according to the different endometrial preparation schemes before frozen embryo transplantation.The transplantation cycle and pregnancy outcome of the two groups were compared.Results (1) There was no statistically significant difference in age,primary infertility rate,infertility years and body mass index (BMI) between the two groups (P ＞ 0.05).(2) In the artificial cycle group,4 cases in which the transplantation was cancelled,including 2 cases who were cancelled due to breakthrough bleeding and 2 cases due to endometrial thickness that were less than 7 mm.There was a statistically significant difference in the cancellation rate between the two groups (x2 =4.13,P =0.04).There were no statistically significant difference in embryo frozen storage time,retrieved oocytes in fresh embryo cycle,frozen thawed embryos in the survival rate,graftage embryonic number,high-quality embryonic rate,endometrium thickness in conversion day (P ＞ 0.05).Estrogen level,luteinizing hormone (LH) levels on endometrium conversion day in GnRH-a down regulation plus artificial cycle group and artificial cycle group were respectively as [(1 439.38 ± 357.43) nmoL/ml vs (1 580.54 ± 479.69) nmol/ml and (2.32 ± 0.94) mIU/ml vs (9.46 ±1.52) mIU/ml],with statistically significant difference (x2 =53.64,P ＜ 0.001;x2 =14.32,P ＜ 0.001).(3) The biochemical pregnancy rates of the patients in the GnRH-a down regulation plus artificial cycle group and artificial cycle group were 72.73％ and 53.23％ respectively,with statistically significant difference (x2 =5.23,P =0.036).The clinical pregnancy rate (65.15％) in GnRH-a down regulation plus artificial cycle group was higher than that of the artificial cycle group (46.77％),with statistically significant difference (x2 =4.39,P =0.022).There was no statistically significant difference in early abortion rate and ectopic pregnancy rate between the two groups.Conclusions In frozen embryo transplantation cycle,long-term GnRH-a down regulation after artificial cycle scheme is superior to simple artificial cycle scheme with significantly reduced cycle cancellation rate,low estrogen and LH levels in endometrium transformation day and higher biochemical pregnancy rate and clinical pregnancy rate.

Objective To investigate the effects of the frozen embryo transplantation for patients with poor outcome of endometrial growth by using growth hormone (GH) intrauterine perfusion combined with replacement cycle in the treatment of thin endometrium.Methods This was a prospective study and study participants were consecutively recruited between Jun 2014 and September 2015.A total of 88 frozen thawed embryo transfer cycles was divided into two groups from the Reproductive Center of Hunan Provincial Maternal and Child Health Hospital.Group A were 63 hormone replacement therapy (HRT) cycles and Group B were 25 GH intrauterine perfusion combined HRT cycles.Results The endometrial thickness of 22 thin endometrium patients from Group B were increased above 7 mm on progesterone day.The endometrial thickness on transplant day of Group A was (9.28 ± 1.64) mm,which was significantly higher than Group B (7.9 ± 0.86) mm (P ＜ 0.05).The clinical pregnancy rate (50.79％ vs 52.0％),implantation rate 31.1％ vs 47.17％),miscarriage rate (9.38％ vs 15.38％) had no significant difference between Groups A and B.The endometrial thickness from 7 mm to 7.9 mm on transplant day,the clinical pregnancy rate (30.76％ vs 54.54％) had no significant difference in two groups (P ＞0.05),but the implantation rate of group A was significantly lower than that of group B (20％ vs 52.17％) (P ＜0.05).When the endometrial thickness was above 8 mm on transplant day,the clinical pregnancy rate (58.33％ vs 63.63％),implantation rate (36.36％ vs 50％) had no significant difference between groups A and B (P ＞ 0.05).Conclusions GH uterine cavity perfusion was a useful method for treatment of thin endometrium,and was helpful for improvement of endometrial thickness and receptivity,improved embryo implantation environment by assistance for HRT under the high estrogen levels.

Objective To compare the clinical efficacy of percutaneous transforaminal endoscopic discectomy (PTED) and Quadrant minimally invasive system in treatment of lumbar disc herniation (LDH). Methods 59 single-level LDH patients were randomly divided into PTED group (n = 31) and Quadrant group (n = 28). Then compare the operative time, incision length, blood loss, length of hospital stay, and the return-to-work time between the two groups. In addition, visual analogue scale (VAS), Japanese Orthopedic Association (JOA), Oswestry disability index (ODI), and modified MacNab criteria were used for surgical efficacy evaluation. Results In PTED group, compared with Quadrant group, we observed, shorter incision length, less blood loss, shorter hospital stay, and shorter time of returning to work (P < 0.05), postoperative VAS, JOA and ODI scores had been improved in both groups (P < 0.05). The PTED group had lower VAS scores of lumbago at 3 days and 1, 3 months postoperatively (P < 0.05). As for postoperative JOA and ODI score, no notable difference was found between the two groups at each corresponding follow-up time point (P > 0.05). According to the improved MacNab criteria, there was no significant difference in excellent or good rate between the two groups (P > 0.05). Conclusion The clinical results of PTED and Quadrant minimally invasive system in treatment of lumbar disc herniation were satisfactory, and PTED were less traumatic method with rapid recovery.