Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.

Objective:To investigate the expression of anaplastic lymphoma kinase (ALK), tropomyosin receptor kinase (TRK), and recombinant C-Ros oncogene 1, receptor tyrosine kinase (ROS1) in Spitz tumors, and to analyze their associations with clinical and histopathological features of Spitz tumors.Methods:Clinical and histopathological characteristics, as well as follow-up data, were collected from patients with Spitz tumors at Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to August 2023, and retrospectively analyzed. Immunohistochemical staining for ALK, pan-TRK, and ROS1 was performed on skin tissues, and associations between the expression of these kinase proteins and clinicopathological features were analyzed.Results:A total of 57 patients with Spitz tumors were collected, including 36 females and 21 males. Immunohistochemical staining showed that 30 (52.6%) patients were positive for ALK, 4 (7.0%) were positive for ROS1, only 2 (3.5%) were positive for TRK, and 21 (36.8%) were negative for the three kinase proteins. Among the 30 ALK-positive patients, the median age was 9.5 years, 21 (70.0%) were females, and 15 (50.0%) presented with lesions on the face, which mainly manifested as papules or nodules; histologically, 29 (96.7%) patients had hypopigmented tumors with an exophytic growth pattern, and the tumor cells were mainly large and long spindle cells arranged in long cord-like, plexiform or fascicular patterns. Among the 4 ROS1-positive patients, there were 3 females and 1 male, presenting with exophytic papules or polyps; histologically, tumor cells were mostly arranged in small nests, without obvious clefts around cell nests. Two TRK-positive patients were both males aged 20 and 50 years respectively, and presented with brown and skin-colored flat papules, respectively; histologically, the tumors were located superficially with a flat base, and tumor cells spread in a pagetoid pattern in the epidermis, with some epithelioid cells and small cell nests. Among the 21 patients negative for the 3 kinase proteins, 9 were males and 12 were females, and they clinically presented with macules, papules and polypoid lesions; histologically, most tumors were located superficially, consisting of a mixture of epithelioid cells and spindle cells, with rare cytological atypia and mitotic figures, and 2 cases showed mild tissue structural and cellular atypia. Fifty-seven patients were followed up for 2 - 83.3 months, with a median follow-up of 19.2 months. Only 1 ALK-positive child experienced a recurrence, and no recurrence or lymph node metastasis was observed in the other cases.Conclusions:Among the three kinase proteins, ALK showed the highest positive rate in Spitz tumors in this study, while TRK- and ROS1-positive cases were sporadic. Histopathologically, ALK-positive Spitz tumor cells were mainly long spindle cells arranged in long cord-like or plexiform patterns, while TRK- and ROS1-positive Spitz tumors tended to have small cell nests. Both the kinase protein-positive and -negative Spitz tumors mostly had a good prognosis.

The problems caused by proximal contact loss(PCL)of dental implants have been a mainstream research topic in recent years,and scholars are unanimously committed to analyzing their causes and related factors,aiming to identify solutions to the problems related to PCL.The effects of the anterior component of force(ACF),the lifelong re-molding of the adult craniofacial jaw and alveolar socket,and the osseointegration characteristics of dental implants are the main causes of PCL.On the one hand,the closing movement of the mandible causes the ACF of the tooth to move through the posterior molar cusp.Moreover,drifting between the upper and lower posterior teeth and mandibular anteri-or teeth can cause the anterior teeth of the upper and lower jaws to be displaced labially.On the other hand,reconstruc-tion of the jaw,alveolar socket and tooth root,the forward horizontal force of the masticatory muscles,the dynamic com-ponent of the jaw and the forward force generated by the oblique plane of the tooth cusp can cause the natural tooth to experience near-middle drift.Additionally,natural teeth can shift horizontally and vertically and rotate to accommodate remodeling of the stomatognathic system and maintain oral function.Nevertheless,the lack of a natural periodontal mem-brane during implant osseointegration,the lack of a physiological basis for near-medium drift,the small average degree of vertical motion and the integrated silence of dental implants without the overall drift characteristics of natural teeth increases the probability of PCL.The high incidence of PCL is clearly associated with the duration of prosthesis delivery and the mesial position;but it is also affected by the magnitude of the bite force,occlusion,the adjacent teeth,restora-tion design,implant location,jaw,and patient age and sex.PCL has shown a significant correlation with food impaction,but not a one-to-one correspondence,and did not meet the necessary and sufficient conditions.PCL is also associated with peri-implant lesions as well as dental caries.PCL prevention included informed consent,regular examinations,se-lection of retention options,point of contact enhancement,occlusal splints,and the application of multipurpose digital crowns.Management of the PCL includes adjacent contact point additions,orthodontic traction,and occlusal adjust-ment.Existing methods can solve the problem of food impaction in the short term with comprehensive intervention to seek stable,long-term effects.Symmetric and balanced considerations will expand the treatment of issues caused by PCL.

Human respiratory syncytial virus (HRSV) is one of the main pathogen causing severe acute lower respiratory tract infections in infants and the elderly, with high incidence rate and mortality worldwide. Vaccine is one of the important measure to prevent infection, transmission and severe disease of HRSV, but currently there is no officially approved preventive vaccine for prevention of HRSV in the world. This paper reviews and analyzes the current research and development progress of HRSV vaccine, summarizes the design routes of different types of HRSV preventive vaccines, and discusses the difficulties and challenges in vaccine research and development, in order to provide reference for the research and development of HRSV vaccine and the development of clinical trials.
Infant ; Humans ; Aged ; Respiratory Syncytial Virus, Human ; Respiratory Syncytial Virus Infections/epidemiology* ; Respiratory Syncytial Virus Vaccines/therapeutic use* ; Respiratory Tract Infections

Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.
Humans ; MicroRNAs/genetics* ; Cicatrix, Hypertrophic/genetics* ; Fibroblasts ; Hyperplasia

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective:To investigate the efficacy of the classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine.Methods:A retrospective case series study was made on 105 patients with single segment facet joint dislocation in subaxial cervical spine admitted to Zhengzhou Orthopedic Hospital from January 2015 to October 2022. There were 63 males and 42 females, with the age range of 22-78 years [(47.5±3.6)years]. Preoperative American Spinal Cord Injury Association (ASIA) classification was grade A in 23 patients, grade B in 45, grade C in 22, grade D in 15 and grade E in 0. The classification of surgical approach was based on the presence or not of continuity between anterior and posterior subaxial cervical structures and the movability of the posterior cervical facet joint on CT two-dimensional images, including anterior cervical surgery if both were presented and posterior facet joint resection plus anterior cervical surgery if there was discontinuity between anterior and posterior subaxial cervical structures or posterior facet joint fusion. Reduction procedures were applied in accordance with the type of facet joint dislocation classified based on the position of the lower upper corner of facet joint, including skull traction or manipulative reduction for the dislocation locating at the dorsal side (type A), intraoperative skull traction and leverage technique for the dislocation locating at the top (type B) and intraoperative skull traction and leverage technique with boosting for the dislocation locating at the ventral side (type C). If the dislocation of two facet joints in the same patient was different, the priority of management followed the order of type C, type B and type A. The reduction success rate, operation time and intraoperative blood loss were recorded. The cervical physiological curvature was evaluated by comparing the intervertebral space height and Cobb angle before operation, at 3 months after operation and at the last follow-up. The fusion rate of intervertebral bone grafting was evaluated by Lenke grading at 3 months after operation. The spinal cord nerve injury was assessed with ASIA classification before operation and at 3 months after operation. Japanese Orthopedic Association (JOA) score was applied to measure the degree of cervical spinal cord dysfunction before operation and at 3 months after operation, and the final follow-up score was used to calculate the rate of spinal cord functional recovery. The occurrence of complications was observed.Results:All patients were followed up for 3-9 months [(6.0±2.5)months]. The reduction success rate was 100%. The operation time was 40-95 minutes [(58.6±9.3)minutes]. The intraoperative blood loss was 40 to 120 ml [(55.7±6.8)ml]. The intervertebral space height was (4.7±0.3)mm and (4.7±0.2)mm at 3 months after operation and at the last follow-up, significantly decreased from preoperative (3.1±0.5)mm (all P<0.01), but there was no significant difference in intervertebral space height at 3 months after operation and at the last follow-up ( P>0.05). The Cobb angle was (6.5±1.3)° and (6.3±1.2)° at 3 months after operation and at the last follow-up, significantly increased from preoperative (-5.4±2.2)° (all P<0.01), but there was no significant difference in Cobb angle at 3 months after operation and at the last follow-up ( P>0.05). The fusion rate of intervertebral bone grafting evaluated by Lenke grading was 100% at 3 months after operation. The ASIA grading was grade A in 15 patients, grade B in 42, grade C in 29, grade D in 12 and grade E in 7 at 3 months after operation. The patients showed varying degrees of improvement in postoperative ASIA grade except that 15 patients with preoperative ASIA grade A had partial recovery of limb sensation but no improvement in ASIA grade. The JOA score was (13.3±0.6)points and (13.1±0.6)points at 3 months after operation and at the last follow-up, significantly improved from preoperative (6.8±1.4)points (all P<0.01), but there was no significant difference in JOA score at 3 months after operation and at the last follow-up ( P>0.05). The rate of spinal cord functional recovery was (66.3±2.5)% at the last follow-up. All patients had no complications such as increased nerve damage or vascular damage. Conclusion:The classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine has advantages of reduced facet joint dislocation, recovered intervertebral space height and physiological curvature, good intervertebral fusion and improved spinal cord function.

Objective:To compare the clinical efficacies of precision targeted and traditional percutaneous vertebroplasty (PVP) in the treatment of refracture of injured vertebra after operation for Kümmell disease.Methods:A retrospective cohort study was conducted to analyze the clinical data of 23 Kümmell disease patients suffering from refracture of injured vertebra after PVP in Zhengzhou Orthopedic Hospital from October 2014 to October 2018. The patients included 7 males and 16 females, aged 53-89 years [(69.3±3.5)years]. There were 11 patients of stage I Kümmell disease and 12 patients of stage II Kümmell disease. The vertebral distribution of fracture was T 11 (3 patients), T 12 (9 patients), L 1 (8 patients) and L 2 (3 patients). Eleven patients received traditional PVP treatment (traditional PVP group) and 12 patients received precision targeted PVP treatment (targeted PVP group). The operation time, amount of bone cement injection and filling of bone cement in the fracture space were compared between the two groups. The visual analogue score (VAS) and Oswestry disability index (ODI) were also compared before operation, at 2 days, 1 month, 3 months, 6 months after operation, and at the last follow-up. The rates of bone cement leakage and re-collapse of injured vertebra were observed in the two groups. Results:The patients were followed up for 12-36 months [(24.2±2.6)months]. There were no significant differences in the operation time or amount of bone cement injection between the two groups (all P>0.05). All the fracture spaces in the targeted PVP group were fully filled with bone cement, while 4 patients in the traditional PVP group showed inadequate filling of the fracture area ( P<0.05). The VAS values in the targeted PVP group were (8.9±0.5)points, (1.6±0.2)points, (1.7±0.1)points, (1.8±0.1)points, (1.9±0.3)points, and (1.8±0.4)points before operation, at 2 days, 1 month, 3 months, 6 months after operation and at the last follow-up; and those in the traditional PVP group were (9.1±0.9)points, (1.8±0.4)points, (1.8±0.2)points, (2.0±0.4)points, (2.1±0.2)points, and (2.4±0.3)points, respectively. The VAS values of both groups were significantly decreased at 2 days, 1 month, 3 months, 6 months after operation, and at the last follow-up compared with those before operation (all P<0.05), but there was no significant difference between different time points after operation (all P>0.05). No significant differences were found in the VAS values between the two groups before operation and at 2 days, 1 month, 3 months and 6 months after operation (all P>0.05). However, the VAS value in the targeted PVP group was significantly lower than that in the traditional PVP group at the last follow-up ( P<0.05). The ODI values in the targeted PVP group were 38.5±4.3, 7.2±2.3, 7.3±2.0, 7.2±1.8, 7.3±2.4, and 7.4±2.5 before operation and at 2 days, 1 month, 3 months, 6 months after operation, and at last follow-up; and those in the traditional PVP group were 37.8±4.1, 7.5±2.5, 7.7±1.9, 7.9±2.4, 8.1±2.6, and 9.6±2.4, respectively. The ODI values of both groups were significantly decreased at 2 days, 1 month, 3 months, 6 months after operation and at the last follow-up compared with those before operation (all P<0.05), but there were no significant differences between different time points after operation (all P>0.05). The ODI values were not significantly different between the two groups before operation and at 2 days, 1 month, 3 months, 6 months after operation (all P>0.05), but the ODI value in the targeted PVP group was significantly lower than that in the traditional PVP group at the last follow-up ( P<0.05). There were no significant differences in the rates of bone cement leakage or re-collapse of injured vertebra between the two groups (all P>0.05). Conclusion:Compared with traditional PVP treatment for refracture of injured vertebra after operation for Kümmell disease, targeted PVP can make bone cement injection fully dispersed, greatly reduce pain and promote functional recovery.

Objective:To investigate the feasibility and therapeutic effect of total knee arthroplasty (TKA) with cruciate-retaining (CR) prosthesis by using FEM-X1 femoral extramedullary positioning instrument based on the theory of restricted kinematic alignment (rKA).Methods:Thirty five cases who underwent total knee arthroplasty in Nanjing Drum Tower Hospital from November 2019 to December 2020 were retrospectively analyzed, including 7 males and 28 females with an average age of 71± 8 years (ranging from 55 to 85 years) Following the guidance of rKA alignment, the FEM-X1 femoral extramedullary positioning instrument was used for TKA with CR prosthesis. Before the operation, the full-length lower limb radiographs of both anteroposterior and lateral views were taken in a standing position for preoperative assessment of lateral distal femoral angle (LDFA), the medial proximal tibial angle (MPTA) and hip-knee-ankle angle (HKA). According to the principle of rKA alignment, the target LDFA, MPTA and HKA were calculated. The proximal end of tibia and distal end of femur were cut using extramedullary positioning instrument respectively. The posterior femoral condyle was cut according to the tibial plateau and mediolateral soft tissue tension. The prosthesis was installed after osteotomy. The release of collateral ligaments, PCL function, release of PCL, patellofemoral trajectory, release of patellofemoral support band, the amount of blood loss and time of operation were recorded. Postoperative LDFA, MPTA, HKA, and posterior slope angle of tibial prosthesis were measured on X-ray images. The Knee Society Score (KSS) was used for functional evaluation.Results:Thirty five cases of TKA with CR prosthesis following rKA alignment were successfully completed. The operation time was 100 (90, 110) min, and the blood loss was 100 (100, 200) ml. 30 of them were followed up for 12.5±0.7 months (ranging from 12 to 14 months). The pre-operative and post-operative LDFA were 1.0°(-2.0°, 4.0°), 0°(-2.0°, 2.0°), MPTA were -4.0°(-5.0°, -1.0°), -2.0°(-3.0°, -1.0°), HKA were -3.0°(-3.0°, -1.0°), -2.0°(-3.0°, -1.0°). There was no significant difference between the three angles before and after operation ( Z=-0.89, P=0.372; Z=1.87, P=0.061; Z=1.03, P=0.302). The average posterior tibial slope was 5°(3°, 7°). At the follow-up of one year, the KSS clinical score was 94(92, 97) and functional score was 80(70, 90) in 30 cases. During the operation, PCL was released in 1 case because of excessive tension; and lateral retinacular release was performed in 1 case because of poor patellofemoral track. Conclusion:ITKA with CR prosthesis by using the extramedullary positioning instrument on the theory of rKA alignment showed a good clinical outcome at a short follow up.